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

Zulpa, Ahmad Khusairy and Muttiah, Barathan and Vellasamy, Kumutha Malar and Mariappan, Vanitha and Vadivelu, Jamuna (2023) Dentatin triggers ROS-mediated apoptosis, G0/G1 cell cycle arrest and release of Th1-related cytokines in colorectal carcinoma cells. Journal of Taibah University for Science, 17 (1). ISSN 1658-3655, DOI https://doi.org/10.1080/16583655.2023.2194231.

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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-alpha and IFN-gamma 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.

Item Type: Article
Funders: Ministry of Education, Malaysia (FRGS/1/2019/SKK15/UM/01/2 (FP109-2019A) )
Uncontrolled Keywords: Dentatin; apoptosis; natural compound; colorectal carcinoma; cytokines
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Medicine
Depositing User: Ms Zaharah Ramly
Date Deposited: 23 Nov 2023 06:56
Last Modified: 23 Nov 2023 06:56
URI: http://eprints.um.edu.my/id/eprint/38240

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