Silibinin Enhances Drug Treatment for Prostate Cancer in Preclinical Studies

by | Apr 11, 2016 | 2003, Cancer, Flavonoids, Men's Health - Prostate

Written by Joyce Smith, BS. A combination treatment of silibinin with cisplatin or carboplatin was significantly more effective in treating prostate cancer than cisplatin or carboplatin when used alone.

Every year, approximately 189,000 men are diagnosed with prostate cancer (PCA) and 30,000 Americans die from this disease. 1 American men have a 5 times greater risk of developing PCA than Japanese men. The traditional Japanese diet is rich in isoflavonoid phytoestrogens commonly found in soy and soy-related foods. 2,3 According to preclinical studies, the flavonoid, silibinin, can inhibit PCA growth and does so with no side effects at in vivo doses 4 ; however, silibinin has little effect on an advanced prostate cancer cell line, PCA DU145. 5 Cancer drugs such as cisplatin* and carboplatin* contain platinum which has anti-cancer activity but is also neurotoxic. Alternative treatments such as combination therapy/prevention strategies can be more efficient and less toxic than these cancer drugs and are therefore gaining popularity. 6

Researchers analyzed the ability of silibinin, cisplatin, and carboplatin, when used in combination, to decrease cell growth and increase apoptosis (programmed cell death) in DU145 cells and explored the molecular mechanisms involved.

Results of various combinations of silibinin and cisplatin or carboplatin on DU145 cell growth and apoptosis (programmed cell death) were as follows:

  • Treating DU145 cells with only silibinin (increasing concentrations of 50-100 uM) decreased cell growth by 36-65%. When treating cells with only cisplatin (2ug/ml), or carboplatin (20ug/ml), cell growth decreased by 48 and 68%, respectively, compared to control.
  • However, when cells were treated with a combination of silibinin (50, 70, or 100uM) and cisplatin (2ug/ml), cell growth decreased by 63-80% (p<0.05, 0.005 and 0.001), respectively, compared to cisplatin alone.
  • The same concentrations of silibinin with carboplatin (20ug/ml) decreased cell growth even more (80-90%), (p< 0.005-0.001) compared to treatment with carboplatin alone.
  • To determine drug effectiveness on cell death, cells were treated with silibinin (100uM), cisplatin (2ug/ml), carboplatin (20 ug/ml) or their combinations. Cell death significantly increased 15 and 40%, respectively with combination treatments. (p<0.001 and 0.05).

Researchers believe these results demonstrate silibinin’s ability to sensitize DU145 cells to treatment with cisplatin or carboplatin and inhibit cell growth while promoting cell death. They also believe additional in vivo studies are needed to hopefully develop more effective treatment strategies for human prostate cancer. Furthermore, since silibinin was nontoxic at the high doses used in these studies and is already used as a dietary supplement, using it in combination with platinum drugs could mean lower and more tolerable drug levels.

*Prescription drugs can save lives but may also cause unwanted side effects.  Consult with your medical healthcare provider for more information on a specific drug of interest.

Source:  Dhanalakshmi, Sivanandhan, et al. “Silibinin sensitizes human prostate carcinoma DU145 cells to cisplatin‐and carboplatin‐induced growth inhibition and apoptotic death.” International journal of cancer 106.5 (2003): 699-705.

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Posted January 20, 2016.

References:

  1. Society AC. Cancer Facts and Figures 2002. American Cancer Society., Inc. 2002;2002:3-15.
  2. Hsing AW, Tsao L, Devesa SS. International trends and patterns of prostate cancer incidence and mortality. International Journal of Cancer. 2000;85(1):60-67.
  3. Adlercreutz H, Honjo H, Higashi A, et al. Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet. The American Journal of Clinical Nutrition. 1991;54(6):1093-1100.
  4. Dhanalakshmi S, Agarwal P, Glode LM, Agarwal R. Silibinin sensitizes human prostate carcinoma DU145 cells to cisplatin‐and carboplatin‐induced growth inhibition and apoptotic death. International journal of cancer. 2003;106(5):699-705.
  5. Zi X, Grasso AW, Kung H-J, Agarwal R. A flavonoid antioxidant, silymarin, inhibits activation of erbB1 signaling and induces cyclin-dependent kinase inhibitors, G1 arrest, and anticarcinogenic effects in human prostate carcinoma DU145 cells. Cancer research. 1998;58(9):1920-1929.
  6. Huan SD, Stewart DJ, Aitken SE, Segal R, Yau JC. Combination of epirubicin and cisplatin in hormone-refractory metastatic prostate cancer. American journal of clinical oncology. 1999;22(5):471.