Dentatin triggers ROS-mediated apoptosis, G0/G1 cell cycle arrest and release of Th1-related cytokines in colorectal carcinoma cells

Abstract

Naturally occurring carbazole alkaloid, Dentatin (DTN), is known to inhibit human cancer cell lines. However, it’s inhibitory and immunomodulatory activities in colorectal carcinoma HCT-116 cells remain obscure. This study compares DTN’s inhibitory effect against 5-FU in HCT-116 cells using in vitro anticancer assays including cell cytotoxicity, migration, colony formation, cell cycle and apoptosis, while assessing its immunomodulatory activity via Th1/Th2/Th17 inflammatory cytokines assay. DTN triggered the intrinsic and extrinsic apoptosis pathways by actuating caspases-8, -9 and -3 while inhibiting cell migration and colonies formation, and inducing cell cycle arrest at the G0/G1 phase. Accumulation of iROS with loss of MMP and DNA damage was observed with elevation of several Th1 cytokines, the TNF-α and IFN-γ with lower pro-inflammatory IL-6 compared to 5-fluorouracil. In conclusion, DTN triggered ROS-mediated apoptosis with release of inflammatory cytokines, potentially evoking anticancer immunity in CRC. Further validation of DTN’s mechanism in vivo is warranted.