Abstract
Silymarin, a widely-used hepatoprotective agent, has shown antitumor properties in
both in vitro and animal studies. Currently, there is limited knowledge regarding silymarinʼs antitelomerase
effects on human colorectal cancer and hepatocyte carcinoma cells. In this study,
we investigated the antiproliferative and antitelomerase effects of silymarin on four
human colorectal cancer and HepG2 hepatocyte carcinoma cell lines. The cell viability
and telomerase activity were assessed using MTT and the telomerase repeat amplification
protocol assay, respectively. We also investigated the effects of silymarin on the
expression of human telomerase reverse transcriptase and its promoter methylation
in HepG2 cells by real-time RT-PCR and methylation-specific PCR, respectively. Silymarin
treatment inhibited cell proliferation and telomerase activity in all cancer cells.
After 24 h of treatment, silymarin exhibited IC50 values ranging from 19 – 56.3 µg/mL against these
cancer cells. A 30-min treatment with silymarin at the IC50 concentration effectively inhibited telomerase activity in cell-free extracts of
both colorectal cancer and hepatocyte carcinoma cells. Treatment of HepG2 cells with
10 and 30 µg/mL of silymarin for 48 h resulted in a decrease in human telomerase reverse
transcriptase expression to 75 and 35% of the level observed in the untreated control
(p < 0.01), respectively. Treatment with silymarin (10, 30, and 60 µg/mL) for 48 h
did not affect human telomerase reverse transcriptase promoter methylation in HepG2
cells. In conclusion, our findings suggest that silymarin inhibits cancer cell growth
by directly inhibiting telomerase activity and downregulating its human telomerase
reverse transcriptase catalytic subunit. However, silymarin did not affect human telomerase
reverse transcriptase promoter methylation at the concentrations of 10 – 60 µg/mL
used in this study.
Keywords
Silybum marianum
- Asteraceae - Telomerase - hTERT - colorectal cancer cells - hepatocarcinoma cells
