Herbal product silibinin-induced programmed cell death is enhanced by metformin in cervical cancer cells at the dose without influence on nonmalignant cells

• A combination of silibinin with metformin is screened in cervical cancer cells.
• It induces inhibition in C-33A cells at a dose no altering nonmalignant cells.
• Increased PTEN and p-AMPK expressions are responsible for apoptosis.
• This finding reveals a potential therapeutic strategy of cervical cancer.

Silibinin is known to display high efficacy against cancer cells and for hepatic protection. Metformin, a well-known antidiabetic agent, has recently been reported to inhibit cancer. In the present study, we investigated the effect of metformin on silibinin-induced programmed cell death in cervical cancer cells (C-33A). MTT assay and Western blot assays were performed to quantify cell viability and the expression of signaling proteins, respectively. Combined treatment with metformin and silibinin decreased cell survival in synergistic manner in C-33A cells at a dose that did not affect nonmalignant cells (HUVECs). Silibinin and metformin increased PTEN and AMPK expression in C-33A cells, respectively. Combined treatment caused a greater increase in the expression of activated caspase-3 or AIF, indicating apoptosis. Combined treatment with silibinin and metformin may induce programmed cell death of human cervical cancer cells at a dose that does not affect HUVECs. This finding reveals a potential therapeutic strategy of cervical cancer.

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