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The Efficacy of Silibinin to Reduce the Impact of Obesity on Invasive Prostate Cancer
Author(s) -
Sherman Blaine,
Hernandez Ana R,
Alani Maraim F,
Price Ramona S
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.300.5
Subject(s) - du145 , prostate cancer , medicine , cancer , silibinin , oncology , cancer research , metastasis , prostate , lncap
Obesity is a risk factor for therapeutic resistance, disease progression, and metastasis in prostate cancer (PCa) patients. Further, obesity results in a state of chronic inflammation, which has been linked, to several types of cancer including the prostate. Previously, we have shown that obesity‐related systemic factors promoted an invasive prostate cancer phenotype, in vitro . Specifically, interleukin‐6 (IL‐6) has been identified as a pro‐inflammatory cytokine, which may mediate obesity‐induced prostate cancer progression. Interestingly, silibinin, a polyphenol found in milk thistle seed, reduces inflammation and may have anti‐tumorigenic properties. The mechanisms involved in obesity‐induced PCa progression are not completely understood, therefore limiting the development of effective interventions to inhibit or reverse the tumor promoting effects of obesity. Therefore, we hypothesize that silibinin may be used to reduce or reverse the impact of obesity on invasive prostate cancer by using an in vitro approach of obesity and cancer. Methods To investigate the efficacy of silibinin to reduce obesity‐induced invasive prostate cancer, a novel in vitro model of obesity and human sera was used. Male human sera from each body mass index (BMI) category (n=5) of normal weight <25 (NW), overweight BMI 25–29.9 (OW), and obese BMI >30 (OB). The prostate cancer cell lines used for this study were PacMetUT1, 22RV1, and DU145. Matrigel chambers were used to measure the invasive capacity of prostate cancer cells. MTT was used to assess cell viability. Immunofluorescence was used to visualize the localization of e‐cadherin. Western blot analysis was used to detect IL‐6, phospho‐Androgen Receptor, total Androgen Receptor and COX‐2. qRT‐PCR was used to evaluate differences in gene expression of IL‐6, phospho‐Androgen, and COX‐2. Student's t ‐test Results PacMetUT1, and 22RV1 cells exposed to serum from obese and overweight sera increased cell viability while silibinin inhibited cell viability. DU145 cell did not differ in cell viability upon exposure to sera from obese, overweight or normal weight with and without silibinin. Silibinin inhibited obesity‐induced invasion in 22RV1, DU145 and PacMetUT1 cells. At the time of the conference, qRT‐PCR and western data analyses will be presented on gene and protein expression of IL‐6, phospho‐Androgen, and COX‐2. Immunofluorescence was used to visualize localization of Ecadherin. In prostate cancer cells exposed to sera from obese sera resulted in dispersion of Ecadherin compared to normal and overweight sera which was modified by exposure to silibinin. Conclusion In summary, silibinin modulates several characteristics from the hallmarks of cancer. Silibinin was effective in selectively inhibiting obesity induced invasion, and suppressed proliferation in several prostate cancer cell lines. Future studies are needed to identify strategies to reverse the impact of obesity on prostate cancer progression.