Abstract 1863: Identification of anticancer agent from antiallergic treatment regimens of traditional Chinese medicine

Abstract

Abstract Traditional Chinese Medicine (TCM) is a holistic system that has been widely used in the treatment of allergy, and several specific herbal formulations have been used as treatment agents. One such compound, berberine, is a plant alkaloid isolated from Phellodendri chinensis. Berberine has been widely used in both Chinese and Ayurvedic medicine and has antimicrobial and antiprotozoal properties. Additional pharmacologic actions reported include anticancer activity as well as anti-inflammatory effects, specifically suppression of proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha. Berberine has been shown to inhibit IgE production in myeloma cell line U266 without cytotoxicity. In U266 berberine inhibits nuclear translocation of NFκB by dampening phosphorylated IκB expression, subsequently decreasing activation of the ϵ-germline transcript promoter and suppressing IgE synthesis. Since this pathway plays a crucial role in many aspects of tumorigenesis, we hypothesized that this could have anticancer activity in solid tumors, specifically melanoma and anaplastic thyroid cancer (ATC). Melanoma and thyroid cancer are diagnosed with a high incidence, increasing over the last few decades. Newer therapies being evaluated in melanoma and thyroid cancer include checkpoint inhibitors. These therapeutic modalities, like others, have off target effects and high relapse rates due to acquired resistance. To identify safer alternative therapeutic strategies we characterized berberine for its anticancer properties through an in vitro proliferation assay with XTT on three melanoma cell lines (SKMEL28, SKMEL37, and SKMEL103), four ATC cell lines (T238, SW1736, HTh74, and 8505C), and three papillary thyroid cancer cell lines (TPC1, BCPAP, and K1). These cell lines were treated with 2μM berberine for 24 hrs. Berberine inhibited cellular proliferation in a dose and time dependent manner in all of these tumor types. ATC cell lines showed more sensitivity towards the drug compared to the other morphotypes. This is specifically significant since therapeutic options for ATC are extremely limited. Both ATC and melanoma have a high nuclear NFκB level, potentially contributing towards their aggressive phenotype. Cells were treated with 2μM berberine and expression of cyclinD1, CDK2, Bcl2, TRAF1, TRAF2 and IAP were evaluated by western blot. Berberine showed a differential regulation of these molecules in melanoma and thyroid cancer. This study opens up a new avenue for the adjuvant treatment of these malignancies using naturally occurring compounds. Citation Format: Tara Jarboe, Michelle Carnazza, Sanjukta Chakraborty, Nan Yang, Kamal Srivastava, Jan Geliebter, Raj K. Tiwari, Xiu-Min Li. Identification of anticancer agent from antiallergic treatment regimens of traditional Chinese medicine [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1863.