Casticin-Induced Inhibition of Cell Growth and Survival Are Mediated through the Dual Modulation of Akt/mTOR Signaling Cascade

Cancers
Jong Hyun LeeKwang Seok Ahn

Abstract

The Akt/mTOR signaling cascade is a critical pathway involved in various physiological and pathological conditions, including regulation of cell proliferation, survival, invasion, and angiogenesis. In the present study, we investigated the anti-neoplastic effects of casticin (CTC), identified from the plant Vitex rotundifolia L., alone and/or in combination with BEZ-235, a dual Akt/mTOR inhibitor in human tumor cells. We found that CTC exerted a significant dose-dependent cytotoxicity and reduced cell proliferation in a variety of human tumor cells. Also, CTC effectively blocked the phosphorylation levels of Akt (Ser473) and mTOR (Ser2448) proteins as well as induced substantial apoptosis. Additionally treatment with CTC and BEZ-235 in conjunction resulted in a greater apoptotic effect than caused by either agent alone thus implicating the anti-neoplastic effects of this novel combination. Overall, the findings suggest that CTC can interfere with Akt/mTOR signaling cascade involved in tumorigenesis and can be used together with pharmacological agents targeting Akt/mTOR pathway.

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Citations

May 6, 2019·Cancers·Samantha Kah Ling OngAnupam Bishayee
Mar 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sun Tae HwangKwang Seok Ahn
Mar 18, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Shanaya RamchandaniKwang Seok Ahn
Jun 7, 2020·International Journal of Molecular Sciences·Milad AshrafizadehGautam Sethi
Aug 31, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Young Yun JungKwang Seok Ahn
Jan 1, 2020·Cancer Cell International·Jingxian LiuKaitai Yao
May 10, 2020·International Journal of Molecular Sciences·Choudhary HarshaAjaikumar B Kunnumakkara
Jan 19, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Zheng-Yu ChengJing-Gung Chung
Jul 8, 2020·International Journal of Molecular Sciences·Young Yun JungKwang Seok Ahn
Dec 18, 2020·Life Sciences·Semim Akhtar AhmedAjaikumar B Kunnumakkara
Sep 26, 2020·Life Sciences·Devivasha BordoloiAjaikuamr B Kunnumakkara
Nov 11, 2020·International Journal of Molecular Sciences·Min Hee YangKwang Seok Ahn
May 1, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Sepideh MirzaeiKwang-Seok Ahn
May 20, 2021·Analytical Cellular Pathology (Amsterdam)·Fan ZhangWen Meng
Aug 8, 2021·International Journal of Molecular Sciences·Young Yun JungKwang Seok Ahn

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Methods Mentioned

BETA
flow cytometry
transfections
transfection
xenograft
protein assay

Software Mentioned

BD Accuri C6 plus
Image J
CalcuSyn

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