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

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.

Diarylpentanoid (1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one) (MS13) Exhibits Anti-proliferative, Apoptosis Induction and Anti-migration Properties on Androgen-independent Human Prostate Cancer by Targeting Cell Cycle–Apoptosis and PI3K Signalling Pathways

“…A greater reduction was noted as the dose was increased to 15.14 µM for DU 145 and 15.60 µM for PC-3 cells. In agreement with the recent study, MS13 induced apoptosis by suppressing the Bcl-2 level in colon cancer cells (Ismail et al, 2020). Similar results were reported when a diarylpentanoid, DM-1 treated in melanoma cells and EF24 in hepatocellular carcinoma cells (Liu et al, 2012;Faião-Flores et al, 2013).…”

“…Besides, MS13 exhibits lower toxicity and highly selective towards PCa cells than normal cells, as indicated by SX values. MS13 showed better cytotoxic activity compared to the parent compound, curcumin against human normal cells, which was consistent with the data described previously (Citalingam et al, 2015;Paulraj et al, 2015;Ismail et al, 2020;Lee et al, 2021). An earlier study reported that FLLL11, which has an identical chemical structure as MS13 was less cytotoxic as curcumin towards human normal cell lines of lung fibroblast (WI-38), bladder smooth muscle and mammary epithelial (non-malignant MCF-10A) (Cen et al, 2009).…”

“…An earlier study reported that FLLL11 induced caspase-3 activity and cleavage of PARP in pancreatic and colorectal cancer cells (Padhye et al, 2010). Recent studies on DAPs also reported that MS13 (Ismail et al, 2020) and B63 (Rajamanickam et al, 2017) induced apoptosis by activating caspase-3 in colon cancer cells. Bcl-2 is an antiapoptotic protein, and its overexpression correlates with tumorigenesis, while its inhibition has been a promising strategy for cancer treatment (García-Aranda et al, 2018).…”

“…Previously, our group has reported that MS13 (1,5-Bis (4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one), a DAP, (Figure 1B demonstrated growth inhibitory effects in time-and dosedependent manner in prostate (Citalingam et al, 2015), cervical (Paulraj et al, 2015), glioblastoma, neuroblastoma (Lee et al, 2021), and colorectal (Ismail et al, 2020) cancer cell lines. Furthermore, MS13 has also shown to be effective than curcumin in inducing apoptosis by modulating apoptosis pathways in gastric (Yoshida et al, 2018), colorectal (Cen et al, 2009) and pancreatic (Friedman et al, 2009) cancer cells.…”

Molecular Mechanisms of Antiproliferative and Apoptosis Activity by 1,5-Bis(4-Hydroxy-3-Methoxyphenyl)1,4-Pentadiene-3-one (MS13) on Human Non-Small Cell Lung Cancer Cells

“…MS13, also known as 1,5-bis(4-hydroxy-3-methoxyphenyl)1,4-pentadiene-3-one, is a mono-ketone derivative that holds α- and β-unsaturated ketone moiety [ 18 ]. This compound has been indicated to exhibit greater cytotoxic effect with lower EC 50 values towards prostate [ 19 ], cervical [ 20 ], colon [ 21 ], glioblastoma, and neuroblastoma [ 22 ] cancer cells. Additionally, MS13 demonstrated its anticancer activity through induction of apoptosis in colon [ 21 ], glioblastoma, and neuroblastoma [ 22 ] cancer cells.…”