Cytotoxic effect of BHMC through ROS pathways on HepG2 and Hs27 cell lines

Mohd Shafiee, Muhammad Aminuddin (2020) Cytotoxic effect of BHMC through ROS pathways on HepG2 and Hs27 cell lines. [Project Paper] (Submitted)

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Abstract

Curcumin is a natural product derived from the turmeric rhizome (Curcuma longa) that possesses a variety of pharmacological properties including antiinflammatory, anti-microbial and anti-cancer activities. It inhibited the inflammatory mediators’ expression, suppressed the cell proliferation and reduced the percentage of invasion and migration in various cancer cell lines. In order to overcome the poor bioavailability of curcumin, several analogues have been synthesised. One of the curcumin analogues is known as 2,6-bis-(4-hydroxyl-3- methoxybenzylidine)cyclohexanone (BHMC). BHMC was synthesised from curcumin by removing the unstable β-diketone moiety and altering it into double bonds while maintaining the phenolic hydroxyl group. Curcumin has been proved to be prooxidant, antioxidant and natural chemoprotective agent that promotes ROS above the threshold level and causes cell death in malignant cells with minimal cytotoxicity effect to normal cells. Reactive oxygen species (ROS) is an unstable oxygen species that easily reacts with other molecules in cells. Increase of ROS level lead to the collapse of redox buffering system, elicited lipid peroxidation and disintegration of the mitochondrial membrane potential that eventually cause cell death in malignant cells. Objective: In this study, the aim is to determine the cytotoxic selective effect of BHMC and curcumin on human liver cancer, HepG2 and non-cancer human fibroblast, Hs27 cell lines through ROS pathways. Methodology: Cell viability of both cell lines treated with BHMC or curcumin were determined using MTT Assay. The accumulation of ROS level in HepG2 cells treated with BHMC was measured using DCFDA Assay. Results and Discussion: BHMC was observed to be approximately three times toxic towards HepG2 cell line compared to curcumin with IC50 of 16.00μM and 46.10μM respectively. However, BHMC was less toxic towards Hs27 cells with IC50 of more than 30μM. Thus, it is suggested that BHMC was cytotoxic selective towards normal cell lines. Further investigation shows that BHMC has a similar pattern in exerting the antioxidant effect as its parental compound. BHMC and curcumin act in dose dependent manner as high antioxidant activity is directly proportional to increase of concentration. Conclusion: BHMC has greater cytotoxic effect towards HepG2 cell line compared to normal Hs27 cell line. Although the exact mechanism is not fully elucidated, BHMC is suggested to trigger its cytotoxicity via ROS pathways.

Item Type:	Project Paper
Faculty:	Faculty of Medicine and Health Science
Depositing User:	Ms. Nor Safa'aton Saidin
Date Deposited:	23 Aug 2023 00:48
Last Modified:	23 Aug 2023 00:48
URI:	http://psaspb.upm.edu.my/id/eprint/1300

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