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Abstract Title:

AKT inhibitor AZD5363 suppresses stemness and promotes anti-cancer activity of 3,3'-diindolylmethane in human breast cancer cells.

Abstract Source:

Toxicol Appl Pharmacol. 2021 Oct 15 ;429:115700. Epub 2021 Aug 28. PMID: 34464674

Abstract Author(s):

Kaiyuan Zhu, Xu Liu, Chunxiao Liu, Yuting Xu, Yingqiang Fu, Wei Dong, Yadong Yan, Wenjing Wang, Cheng Qian

Article Affiliation:

Kaiyuan Zhu

Abstract:

3,3'-diindolylmethane (DIM) is a dimer compound converted from Indoly-3-carbinol that had been studied as promising chemo-preventive agent against breast cancer. In this study, we observed that proportion of CD133Nanogsubpopulation in MCF-7 cells was significantly increased after DIM administration with up-regulated AKT activity by using CyTOF assay. SPADE analysis revealed this stem-like subpopulation exhibited apoptosis-resistance property against DIM treatment. By combining with AKT inhibitor AZD5363, DIM induced CD133 expression could be suppressed. In addition, a combination treatment of MCF-7 and MDA-MB-231 breast cancer cells with DIM and AZD5363 showed synergistic decreases in cell proliferation and induced apoptosis. Furthermore, results from imaging flow cytometry suggested that FoxO3a nuclear localization and PUMA expression could be improved by combination of AZD5363 with DIM. Taken together, the above observations suggested that the combination of AZD5363 with DIM could be developed as potential therapy for breast cancer.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Antiproliferative : CK(6801) : AC(5032)

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