J Sci Food Agric., 2018. , Oct 24. doi: 10.1002/jsfa.9448.

Apoptotic effect of enterodiol, the final metabolite of edible lignans, in colorectal cancer cells.

Shin MK, Jeon YD, Jin JS.

BACKGROUND: Enterodiol (END) is transformed by human intestinal bacteria from lignans contained in various whole-grain cereals, nuts, legumes, flaxseed, and vegetables. END is known to have several physiological effects, but its effects on mitogen-activated protein kinase (MAPK) signaling and apoptosis in colorectal cancer (CRC) cells have not yet been elucidated. Therefore, we investigated the effects of END on apoptosis in CRC cells and whether these effects are mediated via MAPK signaling. RESULTS: Cell proliferation was decreased by END treatment in a time-dependent manner. In particular, END treatment resulted in an apoptosis rate of up to 40% in CT26 cells but showed no cytotoxicity toward RAW264.7 macrophages. END treatment also suppressed the migration of CRC cells in a concentration-dependent manner. The phosphorylation of ERK, JNK, and p38 was down-regulated with END treatment. Furthermore, END decreased the expression levels of anti-apoptotic proteins in CRC cells. CONCLUSION: END inhibited the growth of CRC cells by controlling the MAPK signaling pathway involved in proliferation and apoptosis. These results demonstrate that END has an apoptotic effect in CRC cells.

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Many studies have reported that plant lignans inhibit metastasis and exert anticancer effects in colorectal cancer (CRC) cells. The objective of the present study was to investigate apoptotic properties of END, a lignan metabolite produced by bacteria in the intestinal tract, using colon cancer cell lines. The effects of END were evaluated using the water-soluble tetrazolium 1 (WST-1) assay to monitor cytotoxic effects on mouse CT26 and human HT-29 CRC cells. In addition, underlying mechanisms of apoptosis caused by END were examined expression of the MAPK signaling pathway and Bcl-2 family proteins.

CT26 and HT-29 cells were selected to confirm apoptosis in transformed cells; macrophage RAW264.7 cells were used as normal controls. Mouse CT26 cells originate from the mouse colon adenocarcinoma, where growth rate and metastasis are rapid. END exhibited a time-dependent cytotoxic effect to CT26 and HT-29 cells not observed in untreated cells. Treatment with END (0.01 to 100 μM) further reduced metastatic capacity of the cells in a concentration-dependent manner in vitro. A particularly significant inhibitory effect on migration was observed following treatment with 100 µM END. In conclusion, END, one of the final products of the processing of plant lignans by intestinal bacteria, inhibited proliferation and induced apoptosis in CRC cells. This study showed that consumption of dietary precursor lignans of END could have a beneficial effect on apoptosis in cancer.