The Curcumin Analogue, MS13 (1,5-Bis(4-hydroxy-3- methoxyphenyl)-1,4-pentadiene-3-one), Inhibits Cell Proliferation and Induces Apoptosis in Primary and Metastatic Human Colon Cancer Cells.

Nor Isnida Ismail,Faridah Abas,Rakesh Naidu,Iekhsan Othman,Nordin H Lajis

doi:10.3390/molecules25173798

Abstract

The cytotoxic and apoptotic effects of turmeric (Curcuma longa) on colon cancer have been well documented but specific structural modifications of curcumin have been shown to possess greater growth-suppressive potential on colon cancer than curcumin. Therefore, the aim of this study is to identify the anti-cancer properties of curcumin analogue-MS13, a diarylpentanoid on the cytotoxicity, anti-proliferative and apoptotic activity of primary (SW480) and metastatic (SW620) human colon cancer cells. A cell viability assay showed that MS13 has greater cytotoxicity effect on SW480 (EC50: 7.5 ± 2.8 µM) and SW620 (EC50: 5.7 ± 2.4 µM) compared to curcumin (SW480, EC50: 30.6 ± 1.4 µM) and SW620, EC50: 26.8 ± 2.1 µM). Treatment with MS13 at two different doses 1X EC50 and 2X EC50 suppressed the colon cancer cells growth with lower cytotoxicity against normal cells. A greater anti-proliferative effect was also observed in MS13 treated colon cancer cells compared to curcumin at 48 and 72 h. Subsequent analysis on the induction of apoptosis showed that MS13 treated cells exhibited morphological features associated with apoptosis. The findings are also consistent with cellular apoptotic activities shown by increased caspase-3 activity and decreased Bcl-2 protein level in both colon cancer cell lines. In conclusion, MS13 able to suppress colon cancer cell growth by inhibiting cell proliferation and induce apoptosis in primary and metastatic human colon cancer cells.

Highlights

Colorectal cancer (CRC) currently ranks as the third most prevalent cancer worldwide after lung and breast cancer [1]
Most CRC begins with the silencing of the APC gene which function includes organization of the cytoskeleton, modulation of cell migration, cell cycle and apoptosis regulation, and plays an important role in signal transduction of the Wnt-signaling pathway
The truncated proteins of these critical genes lead to the impairment of apoptosis, enhancement of cellular proliferation and defects in cell cycle control mechanism of the epithelial cells that lining the bowel, which usually leads to the formation of malignant adenomatous polyps as observed in 96% of CRC

Summary

Introduction

Colorectal cancer (CRC) currently ranks as the third most prevalent cancer worldwide after lung and breast cancer [1]. Most CRC begins with the silencing of the APC gene which function includes organization of the cytoskeleton, modulation of cell migration, cell cycle and apoptosis regulation, and plays an important role in signal transduction of the Wnt-signaling pathway. It is involved in a multistep process of mutations causing gene silencing of the tumor suppressor (APC, TP53, and SMAD4/DC4) and mismatch repair (hMSH2, hMLH1, hPMS1, and hMSH6) genes. The truncated proteins of these critical genes lead to the impairment of apoptosis, enhancement of cellular proliferation and defects in cell cycle control mechanism of the epithelial cells (colonocytes) that lining the bowel, which usually leads to the formation of malignant adenomatous polyps as observed in 96% of CRC cases. The malignant polyps may invade, protrude into the bowel wall, metastasize via the lymph and circulatory systems, and cause fatality

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