Chemosensitizer https://greenmedinfo.com/category/keywords/Chemosensitizer en Andrographolide enhances cisplatin-mediated anticancer effects in lung cancer cells. https://greenmedinfo.com/article/andrographolide-enhances-cisplatin-mediated-anticancer-effects-lung-cancer-cel n/a PMID:  Anticancer Drugs. 2017 Jul 7. Epub 2017 Jul 7. PMID: 28692436 Abstract Title:  Andrographolide enhances cisplatin-mediated anticancer effects in lung cancer cells through blockade of autophagy. Abstract:  Lung cancer is the most common cause of cancer-related death worldwide and the platinum-based drugs such as cisplatin have been used as the first line of the treatment. However, the clinical effectiveness of such chemotherapy is limited by intrinsic or acquired resistance. In this study, we found that cisplatin induced autophagy that attenuated the sensitivity of both A549 and Lewis lung cancer (LLC) cells to cisplatin. In contrast, the clinical drug andrographolide (Andro) suppressed autophagy and enhanced cisplatin-mediated apoptosis in these cells. Using two murine lung cancer models, including a subcutaneously inoculated LLC model and an orthotopic LLC implantation model, we investigated the therapeutic efficacy of the combined treatment of cisplatin and Andro. Compared with the sole cisplatin treatment, combining cisplatin with Andro potentially inhibited tumor growth, reduced the incidence of lung metastases, and relieved renal tubular damage. Moreover, the combined treatment prolonged the life span of tumor-bearing mice. TUNEL and immunohistochemistry assays showed the increase in apoptotic cells and the decrease in both conversion of LC3B-I to LC3B-II and Atg5 protein expression in the tumor tissues from mice with the combined treatment. These results suggest that Andro offers an ideal candidate of autophagy inhibitors in clinical application, and combination of cisplatin with Andro could be a promising strategy for the treatment of lung cancer. https://greenmedinfo.com/article/andrographolide-enhances-cisplatin-mediated-anticancer-effects-lung-cancer-cel#comments Andrographolide Lung Cancer Autophagy Inhibitors Chemosensitizer Chemotherapeutic Andrographolidem Autophagy Inhibitors Chemosensitizer Chemotherapeutic Synergy: Cisplatin lung cancer In Vitro Study Wed, 09 Aug 2017 00:17:52 +0000 greenmedinfo 151377 at https://greenmedinfo.com Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance. https://greenmedinfo.com/article/chemo-sensitization-resulting-fasting-may-fact-be-effect-enhanced-immune-surve n/a PMID:  Front Oncol. 2016 ;6:242. Epub 2016 Nov 14. PMID: 27896219 Abstract Title:  Enhanced Therapeutic Efficacy in Cancer Patients by Short-term Fasting: The Autophagy Connection. Abstract:  Preclinical studies suggest that fasting prior to chemotherapy may be an effective strategy to protect patients against the adverse effects of chemo-toxicity. Fasting may also sensitize cancer cells to chemotherapy. It is further suggested that fasting may similarly augment the efficacy of oncolytic viral therapy. The primary mechanism mediating these beneficial effects is thought to relate to the fact that fasting results in a decrease of circulating growth factors. In turn, such fasting cues would prompt normal cells to redirect energy toward cell maintenance and repair processes, rather than growth and proliferation. However, fasting is also known to upregulate autophagy, an evolutionarily conserved catabolic process that is upregulated in response to various cell stressors. Here, we review a number of mechanisms by which fasting-induced autophagy may have an impact on both chemo-tolerance and chemo-sensitization. First, fasting may exert a protective effect by mobilizing autophagic components prior to chemo-induction. In turn, the autophagic apparatus can be repurposed for removing cellular components damaged by chemotherapy. Autophagy also plays a key role in epitope expression as well as in modulating inflammation. Chemo-sensitization resulting from fasting may in fact be an effect of enhanced immune surveillance as a result of better autophagy-dependent epitope processing. Finally, autophagy is involved in host defense against viruses, and aspects of the autophagic process are also often targets for viral subversion. Consequently, altering autophagic flux by fasting may alter viral infectivity. These observations suggest that fasting-induced autophagy may have an impact on therapeutic efficacy in various oncological contexts. https://greenmedinfo.com/article/chemo-sensitization-resulting-fasting-may-fact-be-effect-enhanced-immune-surve#comments Cancers: All Chemosensitizer Fasting/Caloric Restriction Cancer cancer cure Chemosensitizer Chemotherapy Fasting Review Wed, 30 Nov 2016 20:00:24 +0000 greenmedinfo 139654 at https://greenmedinfo.com Curcumin might be a potential adjuvant for non-small-cell lung cancer patients during Paclitaxel treatment. https://greenmedinfo.com/article/curcumin-might-be-potential-adjuvant-non-small-cell-lung-cancer-patients-durin n/a PMID:  Tumour Biol. 2017 Apr ;39(4):1010428317698353. PMID: 28443468 Abstract Title:  Curcumin increases the sensitivity of Paclitaxel-resistant NSCLC cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Abstract:  Non-small-cell lung cancer is one of the most lethal cancers in the worldwide. Although Paclitaxel-based combinational therapies have long been used as a standard treatment in aggressive non-small-cell lung cancers, Paclitaxel resistance emerges as a major clinical problem. It has been demonstrated that Curcumin from Curcuma longa as a traditional Chinese medicine can inhibit cancer cell proliferation. However, the role of Curcumin in Paclitaxel-resistant non-small-cell lung cancer cells is not clear. In this study, we investigated the effect of Curcumin on the Paclitaxel-resistant non-small-cell lung cancer cells and found that Curcumin treatment markedly increased the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel. Mechanically, the study revealed that Curcumin could reduce the expression of metastasis-associated gene 1 (MTA1) gene through upregulation of microRNA-30c in Paclitaxel-resistant non-small-cell lung cancer cells. During the course, MTA1 reduction sensitized Paclitaxel-resistant non-small-cell lung cancer cells and enhanced the effect of Paclitaxel. Taken together, our studies indicate that Curcumin increases the sensitivity of Paclitaxel-resistant non-small-cell lung cancer cells to Paclitaxel through microRNA-30c-mediated MTA1 reduction. Curcumin might be a potential adjuvant for non-small-cell lung cancer patients during Paclitaxel treatment. https://greenmedinfo.com/article/curcumin-might-be-potential-adjuvant-non-small-cell-lung-cancer-patients-durin#comments Carcinoma: Non-Small-Cell Lung Curcumin Chemosensitizer Carcinoma: Non-Small-Cell Lung Chemosensitizer Chemothapeutic Synergy: Paclitaxel CURCUMIN In Vitro Study Fri, 12 May 2017 21:21:10 +0000 greenmedinfo 147682 at https://greenmedinfo.com Diallyl trisulfide suppresses tumor growth and potentiates cisplatin efficacy in gastric cancer treatment. https://greenmedinfo.com/article/diallyl-trisulfide-suppresses-tumor-growth-and-potentiates-cisplatin-efficacy- n/a PMID:  Acta Pharmacol Sin. 2017 Mar 27. Epub 2017 Mar 27. PMID: 28344324 Abstract Title:  Diallyl trisulfide suppresses tumor growth through the attenuation of Nrf2/Akt and activation of p38/JNK and potentiates cisplatin efficacy in gastric cancer treatment. Abstract:  Diallyl trisulfide (DATS), a garlic organosulfide, has shown excellent chemopreventive potential. Cisplatin (DDP) is widely used to treat solid malignant tumors, but causing serious side effects. In the current study, we attempted to elucidate the chemopreventive mechanisms of DATS in human gastric cancer BGC-823 cells in vitro, and to investigate whether DATS could enhance the anti-tumor efficacy of DDP and improve quality of life in BGC-823 xenograft mice in vivo. Treatment with DATS (25-400μmol/L) dose-dependently inhibited the viability of BGC-823 cells in vitro with an IC50 of 115.2±4.3 μmol/L after 24 h drug exposure. DATS (50-200 μmol/L) induced cell cycle arrest at G2/M phase in BGC-823 cells, which correlated with significant accumulation of cyclin A2 and B1. DATS also induced BGC-823 cell apoptosis, which was accompanied by the modulation of Bcl-2 family members and caspase cascade activation. In BGC-823 xenograft mice, administration of DATS (20-40 mg·kg(-1)·d(-1), ip) dose-dependently inhibited tumor growth and markedly reduced the number of Ki-67 positive cells in tumors. Interestingly, combined administration of DATS (30 mg·kg(-1)·d(-1), ip) with DDP (5 mg/kg, every 5 d, ip) exhibited enhanced anti-tumor activity with fewer side effects. We showed that treatment of BGC-823 cells with DATS in vitro and in vivo significantly activated kinases such as p38 and JNK/MAPK and attenuated the Nrf2/Akt pathway. This study provides evidence that DATS exerts anticancer effects and enhances the antitumor efficacy of DDP, making it a novel candidate for adjuvant therapy for gastric cancer. https://greenmedinfo.com/article/diallyl-trisulfide-suppresses-tumor-growth-and-potentiates-cisplatin-efficacy-#comments Dimethyl trisulfide (DMTS) Gastric Cancer Apoptotic Cell cycle arrest Chemosensitizer Apoptotic Cell cycle arrest Chemosensitizer Chemotherapeutic Synergy: Cisplatin Dimethyl trisulfide (DMTS) gastric cancer Animal Study In Vitro Study Tue, 11 Apr 2017 19:57:39 +0000 greenmedinfo 146157 at https://greenmedinfo.com Egyptian sweet orange hesperidin ameliorates the cytotoxic effect of doxorubicin while enhancing its anti-tumor effect. https://greenmedinfo.com/article/egyptian-sweet-orange-hesperidin-ameliorates-cytotoxic-effect-doxorubicin-whil n/a PMID:  Chem Biol Interact. 2018 Apr 1 ;285:76-84. Epub 2018 Feb 23. PMID: 29481770 Abstract Title:  Amelioration effect of Egyptian sweet orange hesperidin on Ehrlich ascites carcinoma (EAC) bearing mice. Abstract:  There are global increased interests to identify novel agents that can possess anti-tumor effects or maximize the anti-tumor effects of low doses for conventional anti-cancer drugs. The aim of this study was to investigate anti-tumor effects and protective role of isolated hesperidin from sweet orange on doxorubicin-induced toxicity in Ehrlich ascites carcinoma (EAC) bearing mice. Tumor cells were injected into Swiss albino mice followed by hesperidin administration either alone or in combination with doxorubicin. Biochemical parameters on serum and hepatic were measured. In addition, the effect of hesperidin on apoptotic genes (Caspase3 and Bax) and anti-apoptotic gene (Bcl2) on tumor cells were evaluated by RT- PCR. The results showed that addition of hesperidin to doxorubicin-induced higher anti-tumor responses than treatment with hesperidin or doxorubicin alone. Hesperidin and doxorubicin in combination prolonged the life span of EAC tumor-bearing mice which was associated with a decrease in the number of viable tumor cells and increases in dead tumor cells number. In addition, co-administration of hesperidin with doxorubicin ameliorated the alteration in serum ALT, AST, ALP, GGT and LDH activities, total protein, albumin, creatinine, urea and total lipids concentrations. Moreover, hesperidin alone and in combination with doxorubicin-treated group decreased hepatic, TBARS level significantly as compared with tumor bearing mice and doxorubicin treated group. In contrast, hesperidin alone and combined with doxorubicin ameliorated total antioxidant capacity, reduced glutathione level, and antioxidant enzymes activities such as GPx and CAT in liver tissues. Moreover, hesperidin induced apoptosis of tumor cells which appeared as DNA fragmentation by down-regulation of Bcl2 as anti-apoptotic gene and stimulation of Caspase3 and Bax genes expression as apoptotic genes. In conclusion, Egyptian citrus peels are a rich source of the antioxidant hesperidin. Moreover, it can ameliorate the cytotoxic effect of doxorubicin while enhancing its anti-tumor effect. https://greenmedinfo.com/article/egyptian-sweet-orange-hesperidin-ameliorates-cytotoxic-effect-doxorubicin-whil#comments Ehrlich carcinoma Hesperidin Sweet Orange Chemoprotective Agents Chemosensitizer Chemoprotective Agents Chemosensitizer Chemotherapeutic Synergy: Doxorubicin Ehrlich carcinoma Hesperidin Sweet Orange Animal Study In Vitro Study Mon, 09 Apr 2018 18:25:41 +0000 greenmedinfo 162373 at https://greenmedinfo.com Inhibition of pyruvate kinase M2 markedly reduces chemoresistance of advanced bladder cancer to cisplatin. https://greenmedinfo.com/article/inhibition-pyruvate-kinase-m2-markedly-reduces-chemoresistance-advanced-bladde n/a PMID:  Sci Rep. 2017 Apr 5 ;7:45983. Epub 2017 Apr 5. PMID: 28378811 Abstract Title:  Inhibition of Pyruvate Kinase M2 Markedly Reduces Chemoresistance of Advanced Bladder Cancer to Cisplatin. Abstract:  Chemoresistance to cisplatin is a principal cause of treatment failure and mortality of advanced bladder cancer (BC). The underlying mechanisms remain unclear, which hinders the development of preventive strategies. Recent data indicate that pyruvate kinase M2 (PKM2), a glycolytic enzyme for Warburg effect, is strongly upregulated in BC. This study explores the role of PKM2 in chemoresistance and whether inhibiting PKM2 augments the chemosensitivity to cisplatin and reduces BC growth and progression. We found that Shikonin binds PKM2 and inhibits BC cell survival in a dose-dependent but pyruvate kinase activity-independent manner. Down-regulation of PKM2 by shRNA blunts cellular responses to shikonin but enhances the responses to cisplatin. Shikonin and cisplatin together exhibit significantly greater inhibition of proliferation and apoptosis than when used alone. Induced cisplatin-resistance is strongly associated with PKM2 overexpression, and cisplatin-resistant cells respond sensitively to shikonin. In syngeneic mice, shikonin and cisplatin together, but not as single-agents, markedly reduces BC growth and metastasis. Based on these data, we conclude that PKM2 overexpression is a key mechanism of chemoresistance of advanced BC to cisplatin. Inhibition of PKM2 via RNAi or chemical inhibitors may be a highly effective approach to overcome chemoresistance and improve the outcome of advanced BC. https://greenmedinfo.com/article/inhibition-pyruvate-kinase-m2-markedly-reduces-chemoresistance-advanced-bladde#comments Bladder Cancer Shikonin Antiproliferative Apoptotic Chemosensitizer Antiproliferative Apoptotic bladder cancer Chemosensitizer Chemotherapeutic Synergy: Cisplatin Dose Response Shikonin In Vitro Study Wed, 03 May 2017 15:21:01 +0000 greenmedinfo 147160 at https://greenmedinfo.com Neferine enhances oxaliplatin sensitivity through an inhibition of EMT in liver cancer cells. https://greenmedinfo.com/article/neferine-enhances-oxaliplatin-sensitivity-through-inhibition-emt-liver-cancer- n/a PMID:  Sci Rep. 2017 Jan 30 ;7:41616. Epub 2017 Jan 30. PMID: 28134289 Abstract Title:  The anti-tumor activities of Neferine on cell invasion and oxaliplatin sensitivity regulated by EMT via Snail signaling in hepatocellular carcinoma. Abstract:  Tumor invasion and chemotherapy resistance, which are associated with epithelial-mesenchymal transition (EMT), remain as major challenges in hepatocellular carcinoma (HCC) treatment. Neferine, a natural component of Nelumbo nucifera, have been proven the antitumor efficiency in cancer, but the effects of Neferine on HCC invasion and chemosensitivity need to be elucidated. Applying multiple assays of cell proliferation, flow cytometry, immunofluorescence staining, qRT-PCR, Western blot, fluorescence molecular tomography imaging, the influences of Neferine on EMT-regulated viability, apoptosis, invasion, and oxaliplatin (OXA) sensitivity were assessed in HCC cells of HepG2 and Bel-7402, as well as in xenograft animal models in vivo. Here, we reported that Neferine had no obvious effects on HCC cells proliferation, but significantly enhanced cytotoxicity and apoptosis caused by OXA in vitro and in vivo. Through an upregulation of E-cadherin and downregulation of Vimentin, Snail and N-cadherin, Neferine suppressed EMT-induced migration and invasion abilities of HCC cells. TGF-β1 cancelled the effects of Neferine on the migration and invasion of HCC cells. Snail overexpression or TGF-β1-induced EMT attenuated Neferine-mediated OXA sensitization in HCC. Together, our data suggest that Neferine enhances oxaliplatin sensitivity through an inhibition of EMT in HCC cells. Neferine may be used as an OXA sensitizer in HCC chemotherapy. https://greenmedinfo.com/article/neferine-enhances-oxaliplatin-sensitivity-through-inhibition-emt-liver-cancer-#comments Liver Cancer Lotus Chemosensitizer Chemosensitizer Chemotherapeutic Synergy: Oxaliplatin liver cancer Lotus In Vitro Study Tue, 21 Feb 2017 18:09:35 +0000 greenmedinfo 143792 at https://greenmedinfo.com Neferine reduces the cisplatin dose requirement in cancer chemotherapy. https://greenmedinfo.com/article/neferine-reduces-cisplatin-dose-requirement-cancer-chemotherapy n/a PMID:  J Cell Biochem. 2017 Feb 18. Epub 2017 Feb 18. PMID: 28214344 Abstract Title:  Neferine Potentiates the Antitumor Effect of Cisplatin in Human Lung Adenocarcinoma Cells via a Mitochondria-mediated Apoptosis Pathway. Abstract:  Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G0/G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome C, p53 levels, then activated cleavage forms of caspase-9, caspase-3 and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. This article is protected by copyright. All rights reserved. https://greenmedinfo.com/article/neferine-reduces-cisplatin-dose-requirement-cancer-chemotherapy#comments Lotus Lung Cancer Apoptotic Chemosensitizer Vascular Endothelial Growth Factor Inhibitors Apoptotic Chemosensitizer Chemotherapeutic Synergy: Cisplatin Lotus lung cancer Vascular Endothelial Growth Factor Inhibitors In Vitro Study Tue, 21 Feb 2017 17:38:48 +0000 greenmedinfo 143784 at https://greenmedinfo.com Neferine revealed higher toxicity toward paclitaxel and doxorubicin-resistant breast, lung or colon cancer cells. https://greenmedinfo.com/article/neferine-revealed-higher-toxicity-toward-paclitaxel-and-doxorubicin-resistant- n/a PMID:  Front Pharmacol. 2017 ;8:238. Epub 2017 May 5. PMID: 28529482 Abstract Title:  Mode of Action Analyses of Neferine, a Bisbenzylisoquinoline Alkaloid of Lotus (Nelumbo nucifera) against Multidrug-Resistant Tumor Cells. Abstract:  Neferine, a bisbenzylisoquinoline alkaloid isolated from the green seed embryos of Lotus (Nelumbo nucifera Gaertn), has been previously shown to have various anti-cancer effects. In the present study, we evaluated the effect of neferine in terms of P-glycoprotein (P-gp) inhibition via in vitro cytotoxicity assays, R123 uptake assays in drug-resistant cancer cells, in silico molecular docking analysis on human P-gp and in silico absorption, distribution, metabolism, and excretion (ADME), quantitative structure activity relationships (QSAR) and toxicity analyses. Lipinski rule of five were mainly considered for the ADME evaluation and the preset descriptors including number of hydrogen bond donor, acceptor, hERG IC50, logp, logD were considered for the QSAR analyses. Neferine revealed higher toxicity toward paclitaxel- and doxorubicin-resistant breast, lung or colon cancer cells, implying collateral sensitivity of these cells toward neferine. Increased R123 uptake was observed in a comparable manner to the control P-gp inhibitor, verapamil. Molecular docking analyses revealed that neferine still interacts with P-gp, even if R123 was pre-bound. Bioinformatical ADME and toxicity analyses revealed that neferine possesses the druggability parameters with no predicted toxicity. In conclusion, neferine may allocate the P-gp drug-binding pocket and prevent R123 binding in agreement with P-gp inhibition experiments, where neferine increased R123 uptake. https://greenmedinfo.com/article/neferine-revealed-higher-toxicity-toward-paclitaxel-and-doxorubicin-resistant-#comments Breast Cancer Cancers: Multi-Drug Resistant Colon Cancer Lotus Lung Cancer Chemosensitizer Chemotherapeutic Breast Cancer Cancers: Multi-Drug Resistant Chemosensitizer Chemotherapeutic COLON CANCER Lotus lung cancer In Vitro Study Wed, 24 May 2017 16:33:00 +0000 greenmedinfo 148177 at https://greenmedinfo.com Resveratrol prevents endothelial cells injury in high-dose interleukin-2 therapy against melanoma. https://greenmedinfo.com/article/resveratrol-prevents-endothelial-cells-injury-high-dose-interleukin-2-therapy- n/a PMID:  PLoS One. 2012 ;7(4):e35650. Epub 2012 Apr 20. PMID: 22532866 Abstract Title:  Resveratrol prevents endothelial cells injury in high-dose interleukin-2 therapy against melanoma. Abstract:  Immunotherapy with high-dose interleukin-2 (HDIL-2) is an effective treatment for patients with metastatic melanoma and renal cell carcinoma. However, it is accompanied by severe toxicity involving endothelial cell injury and induction of vascular leak syndrome (VLS). In this study, we found that resveratrol, a plant polyphenol with anti-inflammatory and anti-cancer properties, was able to prevent the endothelial cell injury and inhibit the development of VLS while improving the efficacy of HDIL-2 therapy in the killing of metastasized melanoma. Specifically, C57BL/6 mice were injected with B16F10 cells followed by resveratrol by gavage the next day and continued treatment with resveratrol once a day. On day 9, mice received HDIL-2. On day 12, mice were evaluated for VLS and tumor metastasis. We found that resveratrol significantly inhibited the development of VLS in lung and liver by protecting endothelial cell integrity and preventing endothelial cells from undergoing apoptosis. The metastasis and growth of the tumor in lung were significantly inhibited by HDIL-2 and HDIL-2 + resveratrol treatment. Notably, HDIL-2 + resveratrol co-treatment was more effective in inhibiting tumor metastasis and growth than HDIL-2 treatment alone. We also analyzed the immune status of Gr-1(+)CD11b(+) myeloid-derived suppressor cells (MDSC) and FoxP3(+)CD4(+) regulatory T cells (Treg). We found that resveratrol induced expansion and suppressive function of MDSC which inhibited the development of VLS after adoptive transfer. However, resveratrol suppressed the HDIL-2-induced expansion of Treg cells. We also found that resveratrol enhanced the susceptibility of melanoma to the cytotoxicity of IL-2-activated killer cells, and induced the expression of the tumor suppressor gene FoxO1. Our results suggested the potential use of resveratrol in HDIL-2 treatment against melanoma. We also demonstrated, for the first time, that MDSC is the dominant suppressor cell than regulatory T cell in the development of VLS. https://greenmedinfo.com/article/resveratrol-prevents-endothelial-cells-injury-high-dose-interleukin-2-therapy-#comments Lung Cancer Melanoma Resveratrol Anti-metastatic Chemoprotective Agents Chemosensitizer Anti-metastatic Chemoprotective Agents Chemosensitizer lung cancer melanoma RESVERATROL In Vitro Study Thu, 20 Jul 2017 00:40:59 +0000 greenmedinfo 150717 at https://greenmedinfo.com Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis. https://greenmedinfo.com/article/sanguinarine-sensitizes-human-gastric-adenocarcinoma-ags-cells-trail-mediated- n/a PMID:  Anticancer Res. 2009 Nov ;29(11):4457-65. PMID: 20032392 Abstract Title:  Sanguinarine sensitizes human gastric adenocarcinoma AGS cells to TRAIL-mediated apoptosis via down-regulation of AKT and activation of caspase-3. Abstract:  Sanguinarine is a benzophenanthridine alkaloid, derived from the root of Sanguinaria canadensis and other poppy Fumaria species, which is known to have antimicrobial, antiinflammatory and antioxidant properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis in cancer cells but spare most normal cells. However, its effects are limited in some types of cancer cells, including AGS human gastric adenocarcinoma cells. In the present study, we showed that treatment with TRAIL in combination with subtoxic concentrations of sanguinarine sensitized TRAIL-mediated apoptosis in AGS cells. Combined treatment with sanguinarine and TRAIL effectively induced Bid cleavage and loss of mitochondrial membrane potential, leading to the activation of caspases, and cleavage of poly(ADP-ribose) polymerase and beta-catenin. The cytotoxic effects of the combined treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. In addition, the levels of Akt protein were markedly reduced in cells co-treated with sanguinarine and TRAIL. Apoptosis induced by the combined treatment was markedly increased by the phosphatidylinositol-3&#039;-kinase inhibitor, LY294002 (Akt-upstream inhibitor), through the mitochondrial amplification step and caspase activation, suggesting that interactions of the synergistic effect were at least partially mediated through the Akt-dependent pathway. https://greenmedinfo.com/article/sanguinarine-sensitizes-human-gastric-adenocarcinoma-ags-cells-trail-mediated-#comments Bloodroot Gastric Cancer Apoptotic Caspase-3 Activation Chemosensitizer Apoptotic Bloodroot Caspase-3 Activation Chemosensitizer gastric cancer In Vitro Study Tue, 31 Jan 2017 00:03:26 +0000 greenmedinfo 142786 at https://greenmedinfo.com Synergistic anti-breast-cancer effects of combined treatment with oleuropein and doxorubicin. https://greenmedinfo.com/article/synergistic-anti-breast-cancer-effects-combined-treatment-oleuropein-and-doxor n/a PMID:  Altern Ther Health Med. 2017 Jun 23. Epub 2017 Jun 23. PMID: 28646810 Abstract Title:  Synergistic Anti-Breast-Cancer Effects of Combined Treatment With Oleuropein and Doxorubicin In Vivo. Abstract:  : Context• Breast cancer is a leading cause of cancer fatalities among women worldwide. Of the more than 80% of patients who receive adjuvant chemotherapy, approximately 40% relapse. The majority of these patients die of disseminated metastatic disease, which emphasizes the need for new therapeutic strategies Objective • The study intended to investigate the anticancer effects of oleuropein (OL) and doxorubicin (DOX) individually and in combination on breast tumor xenografts and also to evaluate the molecular pathways involved. Design • The research team designed in vivo (animal) and in vitro (cell culture) studies. SETTING: The study was performed in the College of Science of King Saud University in the University Center for Women Students (Riyadh, Saudi Arabia). Animals• The study involved 40 female, nude mice (BALB/c OlaHsd-foxn1). Intervention • The mice were injected subcutaneously with MDA-MB-231 human breast cancer cells. After the growth of tumors, the animals were randomly divided into 4 groups to receive intraperitoneal injections: (1) group 1 (controlgroup)-dimethyl sulfoxide, (2) group 2 (intervention group)-50 mg/kg of OL, (3) group 3 (intervention group)-2.5 mg/kg of DOX, and (4) group 4 (intervention group)-1.5 mg/kg of DOX, immediately followed by 50 mg/kg of OL. The OL was extracted from Manzanillo olive trees (Olea europaea) grown in Tabouk, Saudi Arabia. Outcome Measures • The measures included the isolation and primary culture of the tumor xenografts, apoptosis analysis by annexin V, cellular lysate preparation, and immunoblotting. RESULTS: The volume of the tumor increased aggressively, reaching 173 mm3 in the control animals in a time-dependent manner. On the other hand, a sharp drop, to 48.7 mm3, in the volume of the tumor was observed with the 2 drugs combined, a more than 3-fold decrease. The effect was mediated through the induction of apoptosis via the mitochondrial pathway. The combined treatment downregulated the antiapoptosis and proproliferation protein, nuclear factor-kappaΒ, and its main oncogenic target cyclin D1. Furthermore, it inhibited the expression of BCL-2 and survivin. This inhibition could explain the cooperative suppression of the proliferation of breast tumor xenografts and the induction of apoptosis by the combined effect of the compounds used. Conclusions • The key findings clearly indicate the synergistic efficacy of DOX with natural and nontoxic OL against breast tumor xenografts. https://greenmedinfo.com/article/synergistic-anti-breast-cancer-effects-combined-treatment-oleuropein-and-doxor#comments Breast Cancer Oleuropein Chemosensitizer Breast Cancer Chemosensitizer Chemotherapeutic Synergy: Doxorubicin Oleuropein Animal Study Mon, 10 Jul 2017 22:43:51 +0000 greenmedinfo 150264 at https://greenmedinfo.com The combination of centchroman with genistein has selective cytotoxic effect for human breast cancer cell lines. https://greenmedinfo.com/article/combination-centchroman-genistein-has-selective-cytotoxic-effect-human-breast- n/a PMID:  Indian J Pharmacol. 2016 Nov-Dec;48(6):637-642. PMID: 28066099 Abstract Title:  Genistein synergizes centchroman action in human breast cancer cells. Abstract:  OBJECTIVES: Despite the progress in the diagnosis and treatment of breast cancer, it remains a major health problem in women. Natural flavones along with chemotherapeutic agents enhance therapeutic response and minimize toxicity of chemical agents. Centchroman (CC) colloquially called as ormeloxifene, is a nonsteroidal oral contraceptive categorized as selective estrogen receptor modulator with anti-breast cancer activity. Genistein (GN), an isoflavone found mainly in soy products possesses anti-cancerous potential against a number of cancers including breast. The present study aims at investigating the combination of CC and GN in human breast cancer cell lines (HBCCs). MATERIALS AND METHODS: Cytotoxic effect of CC and GN separately and in combination were assessed by sulforhodamine B (SRB) assay in MDA MB-231, MDA MB-468, MCF-7, T-47D HBCCs, and nontumorigenic human mammary epithelial cell (HMEC) MCF-10A. The drug interaction was analyzed using CompuSyn software through which combination index and dose reduction index were generated. RESULTS: Combination of CC plus GN exerts significantly higher cytotoxicity compared to each drug per se in HBCCs, whereas HMEC-MCF-10A remains unaffected. CONCLUSION: On an overall basis, the drugs in combination enhanced cell killing in malignant cells. Therefore, the combination of CC with GN may offer a novel approach for the breast cancer. https://greenmedinfo.com/article/combination-centchroman-genistein-has-selective-cytotoxic-effect-human-breast-#comments Breast Cancer Breast Cancer: Triple Negative Genistein Chemosensitizer Breast Cancer Breast Cancer: Triple Negative Chemosensitizer Genistein Natural Substance/Drug Synergy Selective Cytotoxicity Human In Vitro Mon, 06 Feb 2017 23:51:33 +0000 greenmedinfo 143085 at https://greenmedinfo.com This review describes the role of antioxidants like sulforaphane and curcumin in combatting chemoresistance and chemotherapy-induced oxidative stress through NF-kappaB and HIF-1a inhibition. https://greenmedinfo.com/article/review-describes-role-antioxidants-sulforaphane-and-curcumin-combatting-chemor PMID:  Eur J Pharmacol. 2019 Jun 29 ;859:172513. Epub 2019 Jun 29. PMID: 31260654 Abstract Title:  Combinations of the antioxidants sulforaphane or curcumin and the conventional antineoplastics cisplatin or doxorubicin as prospects for anticancer chemotherapy. Abstract:  Drugs used in clinical oncology have narrow therapeutic indices with adverse toxicity often involving oxidative damage. Chemoresistance to these conventional antineoplastics is usually mediated by oxidative stress-upregulated pathways such as those of nuclear factor-kappa B (NF-κB) and hypoxia-inducible factor-1 alpha (HIF-1α). Accordingly, the use of antioxidants in combinational approaches has begun to be considered for fighting cancer because of both the protective role against adverse effects and the ability to sensitize chemoresistant cancer cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) has been identified as a mediator of the cytoprotection but it is not regularly associated with tumor chemosensitization. However, some Nrf2 inducers could be exerting cytoprotective and chemosensitizing roles through a simple integrated mechanism in which the cellular level of reactive oxygen species is controlled, thus inhibiting the oxidative damage in non-target tissues and the tumor chemoresistance mediated by NF-κB or HIF-1α. As examples to show the general idea of this antioxidant combination chemotherapy, this review explores the preclinical information available for four combinations, each composed by a paradigmatic oncological drug (cisplatin or doxorubicin) and a recognized antioxidant (sulforaphane or curcumin). The issues for translating these outcomes to clinical trials are briefly discussed. <p><a href="https://greenmedinfo.com/article/review-describes-role-antioxidants-sulforaphane-and-curcumin-combatting-chemor" target="_blank">read more</a></p> https://greenmedinfo.com/article/review-describes-role-antioxidants-sulforaphane-and-curcumin-combatting-chemor#comments Broccoli Sprouts Curcumin Sulforaphane Turmeric Anti Inflammatory Antioxidant Effects Chemosensitizer Chemotherapy Hypoxia inducible factor-1 alpha (HIF-1α) inhibitor NF-kappaB Inhibitor Nrf2 activation Anti-cancer Chemoresistance Chemosensitizer Chemotherapy Review Thu, 25 Jul 2019 18:12:16 +0000 greenmedinfo 191873 at https://greenmedinfo.com Vitamin C and K can sensitize cancer cells to conventional chemotherapy. https://greenmedinfo.com/article/vitamin-c-and-k-can-sensitize-cancer-cells-conventional-chemotherapy n/a PMID:  Redox Biol. 2018 Mar 20 ;16:352-358. Epub 2018 Mar 20. PMID: 29597144 Abstract Title:  Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect. Abstract:  This review is directed to the redox-modulating properties and anticancer effect of vitamin K. The concept is focused on two aspects: (i) redox-cycle of vitamin K and its effect on the calcium homeostasis,&quot;oncogenic&quot;and&quot;onco-suppressive&quot;reactive oxygen species and the specific induction of oxidative stress in cancer; (ii) vitamin K plus C as a powerful redox-system, which forms a bypass between mitochondrial complexes II and III and thus prevents mitochondrial dysfunction, restores oxidative phosphorylation and aerobic glycolysis, modulates the redox-state of endogenous redox-pairs, eliminates the hypoxic environment of cancer cells and induces cell death. The analyzed data suggest that vitamin C&amp;K can sensitize cancer cells to conventional chemotherapy, which allows achievement of a lower effective dose of the drug and minimizing the harmful side-effects. The review is intended for a wide audience of readers - from students to specialists in the field. https://greenmedinfo.com/article/vitamin-c-and-k-can-sensitize-cancer-cells-conventional-chemotherapy#comments Cancers: All Vitamin C Vitamin K Chemosensitizer Cancers: All Chemosensitizer Vitamin C Vitamin K Review Sat, 07 Apr 2018 14:27:27 +0000 greenmedinfo 162336 at https://greenmedinfo.com