Journal
MOLECULES
Volume 26, Issue 2, Pages -Publisher
MDPI
DOI: 10.3390/molecules26020376
Keywords
colorectal cancer; HCT 116; telomerase; telomerase inhibitor; berberine; downregulation; cell cycle arrest; telomere erosion
Funding
- Universiti Malaya, Malaysia [RP030C-15AFR, RU004C-2020, CEBAR RU006-2018]
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This study found that berberine can decrease telomerase activity and level in HCT 116 cells, which subsequently inhibits the proliferative ability of the cells.
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.
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