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Abstract Title:

Piperlongumine induces ROS mediated apoptosis by transcriptional regulation of SMAD4/P21/P53 genes and synergizes with doxorubicin in osteosarcoma cells.

Abstract Source:

Chem Biol Interact. 2022 Feb 25 ;354:109832. Epub 2022 Jan 24. PMID: 35085581

Abstract Author(s):

Laxminarayan Rawat, Vijayashree Nayak

Article Affiliation:

Laxminarayan Rawat

Abstract:

Piperlongumine is a herbal drug, with well-known anti-microbial and anti-neoplastic properties. The anti-carcinogenic potential of piperlongumine has been extensively explored for breast, colorectal, lungs, pancreatic, prostate, and oral carcinoma. However, a few numbers of studies are available on its bio-activity in osteosarcoma. Therefore, the present study aimed at exploring the therapeutic potential and possible mechanisms of action of piperlongumine in three human osteosarcoma cell lines in-vitro. The cytotoxicity of piperlongumine was determined by MTT assay, which shows dose and time-dependent inhibition of MG-63, 143B and KHOS/NP cells. Piperlongumine arrest the cells in G2/M phase of cell cycle and increases reactive oxygen species production, which possibly leads to lethal oxidative stress and apoptosis. Piperlongumine treatment significantly upregulated the expression of genes BAX, P21, P53, and SMAD4; while the BCL-2, SURVIVIN, TNFA, and NFKB genes expression was found down-regulated. Furthermore, piperlongumine exposure inhibited the migration of osteosarcoma cells as the expression of migration marker genes CDH2, CTNNB1, FN1, and TWIST were found to be down-regulated. The drug combination studies show the synergistic effect of piperlongumine with the conventional chemotherapeutic drug doxorubicin in osteosarcoma cells. Taken together, the above results suggest that PL displays anticancer properties against osteosarcoma and can be used as a therapeutic agent for osteosarcoma treatment in clinical settings.

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