Dentatin triggers ROS-mediated apoptosis, G0/G1 cell cycle arrest and release of Th1-related cytokines in colorectal carcinoma cells. Issue 1 (31st December 2023)

• Record Type: Journal Article
• Authors: Zulpa, Ahmad Khusairy; Muttiah, Barathan; Vellasamy, Kumutha Malar; Mariappan, Vanitha; Vadivelu, Jamuna
• Is Part Of: Journal of Taibah University for science. Volume 17:Issue 1(2023)
• Publication Date: 2023-12-31
• Subjects: Dentatin -- apoptosis -- natural compound -- colorectal carcinoma -- cytokines; Science -- Periodicals; Science; Periodicals; 505
• DOI: 10.1080/16583655.2023.2194231
• Languages: English
• ISSNs: 1658-3655

Abstract

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.