Anti-Cancer Effects of α-Cubebenoate Derived from Schisandra chinensis in CT26 Colon Cancer Cells.

Yun Ju Choi,Jeong Eun Gong,Ji Eun Kim,You Jeong Jin,Young Whan Choi,Dae Youn Hwang,Sun Il Choi,Su Jin Lee

doi:10.3390/molecules27030737

Yun Ju Choi, Jeong Eun Gong + Show 6 more

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https://doi.org/10.3390/molecules27030737

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Abstract

α-Cubebenoate derived from Schisandra chinensis has been reported to possess anti-allergic, anti-obesity, and anti-inflammatory effects and to exhibit anti-septic activity, but its anti-cancer effects have not been investigated. To examine the anti-cancer activity of α-cubebenoate, we investigated its effects on the proliferation, apoptosis, and metastasis of CT26 cells. The viabilities of CT26 cells (a murine colorectal carcinoma cell line) and HCT116 cells (a human colon cancer cell line) were remarkably and dose-dependently diminished by α-cubebenoate, whereas the viability of CCD-18Co cells (a normal human fibroblast cell line) were unaffected. Furthermore, α-cubebenoate treatment increased the number of apoptotic CT26 cells as compared with Vehicle-treated cells and increased Bax, Bcl-2, Cas-3, and Cleaved Cas-3 protein levels by activating the MAP kinase signaling pathway. α-Cubebenoate also suppressed CT26 migration by regulating the PI3K/AKT signaling pathway. Furthermore, similar reductions were observed in the expression levels of some migration-related proteins including VEGFA, MMP2, and MMP9. Furthermore, reduced VEGFA expression was found to be accompanied by the phosphorylations of FAK and MLC in the downstream signaling pathway of adhesion protein. The results of the present study provide novel evidence that α-cubebenoate can stimulate apoptosis and inhibit metastasis by regulating the MAPK, PI3K/AKT, and FAK/MLC signaling pathways.

Highlights

Natural products derived from microbes, plants, and marine organisms are considered major resources of potential chemotherapeutic agents [1]
We investigated whether α-cubebenoate elicited toxic effects in CCD-18Co and CT26 cells using MTT assays after exposing cells to three different concentrations, that is, 7.5 μg/mL α-cubebenoate (Low dose α-cubebenoate, LoCb), 15 μg/mL α-cubebenoate, or 30 μg/mL α-cubebenoate for 24 h
The viability of CT26 cancer cells was remarkably and dose-dependently reduced by α-cubebenoate, and this reduction was slightly higher in the HiCb group than the Cis group (5 μg/mL of cisplatin) (Figure 1b)

Summary

Introduction

Natural products derived from microbes, plants, and marine organisms are considered major resources of potential chemotherapeutic agents [1]. The effects of S. chinensis are associated with the dibenzo cyclooctadiene lignans, which include schisandrin, schisantherins A, B, and C, γ-schisandrin, schisanthenol, deoxyschisandrin, and gomisins A and G [9,10]. The structures of these compounds were elucidated using various NMR techniques such as polarization transfer (DEPT), heteronuclear multiple bond correlations (HMBCs), and heteronuclear single quantum coherence (HSQC) [11]

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