J Appl Biomed 13:113-121, 2015 | DOI: 10.1016/j.jab.2014.11.001

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

Wen-Shiung Lioua, Li-Jen Chenb, Ho-Shan Niub, Ting-Ting Yangc, Juei-Tang Chengd,f,*, Kao-Chang Line,g,*
a Department of Obstetrics & Gynecology, Kaohsiung Veterans General Hospital, Kaohsiung City 81301, Taiwan
b Department of Nursing, Tzu Chi College of Technology, Hualien City 97005, Taiwan
c The School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung City 82401, Taiwan
d Department of Medical Research, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan
e Department of Neurology, Chi-Mei Medical Center, Yong Kang, Tainan City 71003, Taiwan
f Institute of Medical Sciences, Chang Jung Christian University, Gueiren, Tainan City 71101, Taiwan
g Institute of Biotechnology, Southern Taiwan University, Yong Kang, Tainan City 71004, Taiwan

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.

Keywords: Silibinin; Metformin; C-33A; Apoptosis; Cervical cancer

Received: August 13, 2014; Revised: November 17, 2014; Accepted: November 19, 2014; Published: May 1, 2015  Show citation

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Liou W, Chen L, Niu H, Yang T, Cheng J, Lin K. Herbal product silibinin-induced programmed cell death is enhanced by metformin in cervical cancer cells at the dose without influence on nonmalignant cells. J Appl Biomed. 2015;13(2):113-121. doi: 10.1016/j.jab.2014.11.001.
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