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

Jong Lee,Kwang Ahn,Gautam Sethi,Chulwon Kim,Jae-Young Um

doi:10.3390/cancers11020254

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.

Highlights

Most people diagnosed with cancers are treated with chemotherapy, surgery, radiation therapy.They may receive immunotherapy, targeted and hormonal therapies
We found that the cell viability decreased in a dose-dependent manner in cells treated with CTC
The data showed that CTC inhibited cell proliferation in in a time-dependent manner in three cancer cell lines (Figure 1B-ii)

Summary

Introduction

Most people diagnosed with cancers are treated with chemotherapy, surgery, radiation therapy. They may receive immunotherapy, targeted and hormonal therapies. In the case of radiation and chemotherapy, it is difficult to avoid side effects because these treatments can affect normal rapidly growing cells [1,2]. Many novel cancer therapies are currently being developed worldwide and the goal is to achieve optimum treatment for the patients with relatively lower side effects. Natural compounds can be obtained from a variety of sources, including plants [3], animals [4], microorganisms [5], and can be employed as pharmacological agents for cancer treatment [6,7,8]. Natural compounds with broad modes of action are being explored for their potential to treat various malignancies [4,9,10,11,12,13,14,15,16]

Methods

Results

Conclusion