Abstract

Colorectal cancer (CRC) is the most prevalent cause of cancer death and incidence in Taiwan. It has been known for several decades that carcinomas mostly develop from adenomas, early symptom is not easy to diagnosis, but lately stage almost has metastasis and worse prognosis. Incidence of CRC has been considered to be related to daily food strongly. Chemoprevention by dietary compounds has received considerable attention as an effective approach for cancer prevention. Among the dietary indole compound indole-3-carbinol (I3C) present in the Brassica plants, including broccoli, cabbage and cauliflower, I3C is biologically active, and it is converted into 3,3’-diindolylmethane (DIM) under pH5-7, which is also biologically active. In various cancer cells, I3C and DIM has exhibited anti-cancer effects, including cell cycle inhibition, apoptosis. In our previous study, we suggested expression of Daxx may play an important role in CRC carcinogenesis and metastasis. It is interesting to investigate what a different cellular response with indole compound intake in different expression level of Daxx in Hct116. So we established sh-Daxx Hct116 cells (Daxx stable knock down cell line) and sh-Luci Hct116 cells (stable control cell line) to clarify this question. The cellular viability had been measured by trypan blue stain. Daxx knock down cell had a better tolerability with indole compound intake and suggested Daxx promote cellular death induced by indole compound. Furthermore, the induction of Caspase-8 mediated apoptosis in sh-Luci and sh-Daxx stable cells treated with indole compound was different and detected by western blot. We had also shown that expression of MAPK and pro-apoptotic proteins like p-p38 were increased by DIM treatment. Above of all findings, expression of Daxx might alter cellular response of indole compound through activation of Caspase-8. We demonstrate that I3C and DIM-induced apoptosis in Hct116 cells. Daxx play an important role, resulting in the induction of the Caspase-8 pathway.

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