The Effects of Concomitant use of Silymarin and Chemotherapy on Solid Tumors: A pilot randomized controlled trial
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Sanambar Sadighi
,
Simin Dashti-Khavidaki
,
Foroud Shahbazi
,
Mehrzad Mirzania
,
Farhad Shahi
,
Alireza Abdollahi
,
Mohammad Hossein Ghahremani
Abstract
Anti-cancer potential of silymarin have been shown in cell culture. However, regarding this matter no prospective clinical study has been done. In a randomized double blind pilot study, we compared effects of addition of standard chemotherapy along with silymarin (420mg/day) versus placebo on clinical response of advanced tumors after three cycles of cisplatin-based chemotherapy. There was no significant difference in tumor size after three consecutive chemotherapy courses but a trend toward lower metastasis rate in chemotherapy + silymarin group. Concomitant use of silymarin along with chemotherapy was very well tolerated but didn’t significantly increase clinical response. Due to trend toward significant lower metastasis in silymarin group, further study with larger sample size is needed to better clarify probable role of adjunctive therapy with silymarin in patients with solid tumors.Vladimir Kren, Daniela Walterova. Silybin and silymarin- new effects and applications. Biomed Papers 2005; 149:29-41
Gazák R, Walterová D, Kren V. Silybin and silymarin--new and emerging applications in medicine. Current Medicinal Chemistry, 2007; 14: 315-338.
Féher J, Lengyel G.Silymarin in the prevention and treatment of liver diseases and primary liver cancer. Curr Pharm Biotechnol. 2012; 13:210-7.
Singh, R.P.; Agarwal, R. Flavonoid antioxidant silymarin and skin cancer. Antioxid Redox Signal 2002; 4:655–663.
Katiyar SK. Silymarin and skin cancer prevention: anti-inflammatory, antioxidant and immunomodulatory effects (Review).Int J Oncol. 2005; 26:169-76.
Vaid M, Katiyar SK. Molecular mechanisms of inhibition of photocarcinogenesis by silymarin, a phytochemical from milk thistle (Silybum marianum L. Gaertn.) (Review). Int J Oncol. 2010; 36:1053-60.
Ramasamy K, Agarwal R. Multitargeted therapy of cancer by silymarin. Cancer Lett 2008; 269: 352-62.
Kim S, Choi JH, Lim HI, et al. Silibinin prevents TPA-induced MMP-9 expression and VEGF secretion by inactivation of the Raf/MEK/ERK pathway in MCF-7 human breast cancer cells. Phytomedicine 2009; 16: 573-80.
Sharma, G.; Singh, R.P.; Chan, D.C.; Agarwal, R. Silibinin induces growth inhibition and apoptotic cell death in human lung carcinoma cells. Anticancer Res 2003, 23, 2649–2655.
Qi WX, Shen Z, Tang LN, Yao Y. The role of anti-VEGF agents in the treatment of advanced gastric cancer: a meta-analysis of randomized controlled trials. Tumour Biol. 2014; 35:7675-83.
Li L, Wang L, Zhang W, Tang B, et al. Correlation of serum VEGF levels with clinical stage, therapy efficacy, tumor metastasis and patient survival in ovarian cancer. Anticancer Res 2004; 24:1973-9.
Cheng D, Liang B, Li Y. Serum vascular endothelial growth factor (VEGF-C) as a diagnostic and prognostic marker in patients with ovarian cancer. PLoS One 2013; 8:e55309.
Shahbazi F1, Sadighi S2, Dashti-Khavidaki S, et al. Effect of Silymarin Administration on Cisplatin Nephrotoxicity: Report from A Pilot, Randomized, Double-Blinded, Placebo-Controlled Clinical Trial. Phytother Res. 2015; 29:1046-53.
Eisenhauer EA1, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009; 45:228-47.
Jiang C, Agarwal R, Lü J. Anti-angiogenic potential of a cancer chemopreventive flavonoid antioxidant, silymarin: inhibition of key attributes of vascular endothelial cells and angiogenic cytokine secretion by cancer epithelial cells. Biochem Biophys Res Commun. 2000 16; 276:371-8.
Yang SH, Lin JK, Chen WS, et al. Anti-angiogenic effect of silymarin on colon cancer LoVo cell line. J Surg Res. 2003; 113:133-8.
Agarwal R, Agarwal C, Ichikawa H, et al. Anticancer potential of silymarin: from bench to bed side. Anticancer Res. 2006; 26:4457-98.
Gallo D, Giacomelli S, Ferlini C, et al. Antitumour activity of the silybin-phosphatidylcholine complex, IdB 1016, against human ovarian cancer. Eur J Cancer. 2003; 39:2403-10.
Qi L, Singh RP, Lu Y, et al. Epidermal growth factor receptor mediates silibinin-induced cytotoxicity in a rat glioma cell line. Cancer Biol Ther. 2003; 2:526-31.
Singh RP, Sharma G, Dhanalakshmi S, et al. Suppression of advanced human prostate tumor growth in athymic mice by silibinin feeding is associated with reduced cell proliferation, increased apoptosis, and inhibition of angiogenesis. Cancer Epidemiol Biomarkers Prev. 2003; 12:933-9.
Singh RP, Raina K, Deep G, et al. Silibinin suppresses growth of human prostate carcinoma PC-3 orthotopic xenograft via activation of extracellular signal-regulated kinase 1/2 and inhibition of signal transducers and activators of transcription signaling. Clin Cancer Res. 2009; 15:613-21.
Kaleeswaran S1, Sriram P, Prabhu D; Chinnathambi, et al. Anti- and pro-mutagenic effects of silymarin in the Ames bacterial reverse mutation assay. Phytother Res. 2009; 23:1378-84.
Li W, Mu D, Song L, et al. Molecular mechanism of silymarin-induced apoptosis in a highly metastatic lung cancer cell line anip973.Cancer Biother Radiopharm. 2011; 26:317-24.
Deep G, Agarwal R Antimetastatic efficacy of silibinin: molecular mechanisms and therapeutic potential against cancer. Cancer Metastasis Rev. 2010; 29:447-63.
Li F, Ma Z, Guan Z. Autophagy induction by silibinin positively contributes to its anti-metastatic capacity via AMPK/mTOR pathway in renal cell carcinoma. Int J Mol Sci. 2015 15; 16:8415-29.
Vaid M, Singh T, Prasad R, et al. Silymarin inhibits melanoma cell growth both in vitro and in vivo by targeting cell cycle regulators, angiogenic biomarkers and induction of apoptosis. Mol Carcinog. 2014 Aug 30. doi: 10.1002/mc.22208. [Epub ahead of print]
Kim S, Choi MG, Lee HS, et al. Silibinin suppresses TNF-alpha-induced MMP-9 expression in gastric cancer cells through inhibition of the MAPK pathway. Molecules. 2009; 14:4300-11.
Gu M, Dhanalakshmi S, Mohan S, et al. Silibinin inhibits ultraviolet B radiation-induced mitogenic and survival signaling, and associated biological responses in SKH-1 mouse skin. Carcinogenesis. 2005; 26:1404-13.
Zhao J, Agarwal R. Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis 1999; 20:2101-8.
Ladas EJ, Kroll DJ, Oberlies NH, Cheng B, et al. A randomized controlled, double-blind pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL). Cancer 2010; 116: 506–513.
Siegel AB, Narayan R,Rodriguez R, Goyal A et al. A Phase I Dose-Finding Study of SilybinPhosphatidylcholine (Milk Thistle) in Patients With Advanced Hepatocellular Carcinoma. Integr Cancer Ther. 2014; 13: 46–53.
| Files | ||
| Issue | Vol 9 No 2 (2017) | |
| Section | Original Articles | |
| Keywords | ||
| silymarin anticancer solid tumor chemotherapy | ||
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