Berberine inhibits telomerase activity and induces cell cycle arrest and telomere erosion in colorectal cancer cell line, HCT 116

Samad, Muhammad Azizan and Saiman, Mohd Zuwairi and Abdul Majid, Nazia and Karsani, Saiful Anuar and Yaacob, Jamilah Syafawati (2021) Berberine inhibits telomerase activity and induces cell cycle arrest and telomere erosion in colorectal cancer cell line, HCT 116. Molecules, 26 (2). ISSN 1420-3049, DOI https://doi.org/10.3390/molecules26020376.

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Abstract

Colorectal cancer (CRC) is the most common cancer among males and females, which is associated with the increment of telomerase level and activity. Some plant-derived compounds are telomerase inhibitors that have the potential to decrease telomerase activity and/or level in various cancer cell lines. Unfortunately, a deeper understanding of the effects of telomerase inhibitor compound(s) on CRC cells is still lacking. Therefore, in this study, the aspects of telomerase inhibitors on a CRC cell line (HCT 116) were investigated. Screening on HCT 116 at 48 h showed that berberine (10.30 +/- 0.89 mu g/mL) is the most effective (lowest IC50 value) telomerase inhibitor compared to boldine (37.87 +/- 3.12 mu g/mL) and silymarin (>200 mu g/mL). Further analyses exhibited that berberine treatment caused G(0)/G(1) phase arrest at 48 h due to high cyclin D1 (CCND1) and low cyclin-dependent kinase 4 (CDK4) protein and mRNA levels, simultaneous downregulation of human telomerase reverse transcriptase (TERT) mRNA and human telomerase RNA component (TERC) levels, as well as a decrease in the TERT protein level and telomerase activity. The effect of berberine treatment on the cell cycle was time dependent as it resulted in a delayed cell cycle and doubling time by 2.18-fold. Telomerase activity and level was significantly decreased, and telomere erosion followed suit. In summary, our findings suggested that berberine could decrease telomerase activity and level of HCT 116, which in turn inhibits the proliferative ability of the cells.

Item Type: Article
Funders: Universiti Malaya, Malaysia (RP030C-15AFR) (RU004C-2020) (CEBAR RU006-2018)
Uncontrolled Keywords: Colorectal cancer; HCT 116; Telomerase; Telomerase inhibitor; Berberine; Downregulation; Cell cycle arrest; Telomere erosion
Subjects: Q Science > QD Chemistry
Divisions: Faculty of Science
Depositing User: Ms Zaharah Ramly
Date Deposited: 08 Mar 2022 01:40
Last Modified: 08 Mar 2022 01:40
URI: http://eprints.um.edu.my/id/eprint/27856

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