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Increase of Phosphatase and Tensin Homolog by Silymarin to Inhibit Human Pharynx Squamous Cancer

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Journal J Med Food
Date 2013 Aug 6
PMID 23909904
Citations 11
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Abstract

Silymarin is an active principle from the seeds of the milk thistle plant and is widely used as a hepatoprotective gent due to its antioxidant-like activity. In the present study, we evaluated the potential efficacy of silymarin against oral cancer and investigated its possible mechanism of action. Cell viability assay and western blotting analyses were used to identify silymarin-induced apoptotic cell death in human pharynx squamous cell carcinoma (FaDu) cells. The short interfering RNA (siRNA) is used to confirm the role of phosphatase and tensin homolog (PTEN) in silymarin-induced apoptosis. Treatment of FaDu cells with silymarin resulted in a significant decrease in cell viability (up to 70%). Silymarin inhibited the phosphorylation of Akt (over 10-fold) with an increase in expression of PTEN (five to sixfold). Consequently, the level of Bcl-2 expression was decreased five to sixfold and caspase 3 activated to induce apoptosis. Treatment with siRNA specific to PTEN gene diminished the action of silymarin. The results suggest that silymarin inhibits the Akt signaling pathway by increasing PTEN expression in FaDu cells and directly affects Bcl-2 family members. Also, we demonstrated the inhibitory activity of silymarin for oral cancer is related to cell survival. These mechanisms may in part explain the actions of silymarin and provide a rationale for the development of silymarin as an anticancer agent.

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References
1.
Zhong X, Zhu Y, Lu Q, Zhang J, Ge Z, Zheng S . Silymarin causes caspases activation and apoptosis in K562 leukemia cells through inactivation of Akt pathway. Toxicology. 2006; 227(3):211-6. DOI: 10.1016/j.tox.2006.07.021. View

2.
Nukatsuka M, Saito H, Sakamoto K, Nakagawa F, Uchida J, Kobunai T . Efficacy of combination chemotherapy using oral fluoropyrimidine S-1 with oxaliplatin (SOX) against colorectal cancer in vivo. Anticancer Res. 2012; 32(7):2807-12. View

3.
Ramasamy K, Agarwal R . Multitargeted therapy of cancer by silymarin. Cancer Lett. 2008; 269(2):352-62. PMC: 2612997. DOI: 10.1016/j.canlet.2008.03.053. View

4.
Workman P, Clarke P, Raynaud F, van Montfort R . Drugging the PI3 kinome: from chemical tools to drugs in the clinic. Cancer Res. 2010; 70(6):2146-57. PMC: 3242038. DOI: 10.1158/0008-5472.CAN-09-4355. View

5.
Singh R, Agarwal R . A cancer chemopreventive agent silibinin, targets mitogenic and survival signaling in prostate cancer. Mutat Res. 2004; 555(1-2):21-32. DOI: 10.1016/j.mrfmmm.2004.05.017. View