Abstract 3728: Astaxanthin as an adjunct therapy for breast cancer

Abstract

Abstract While existing treatment regimens for breast cancer have increased patient survival, regional recurrence and metastasis remain a significant clinical problem. Many current therapies exhibit dose-limiting toxicities, so the development of adjuvant therapeutic strategies which can improve the efficacies and/or reduce the side effects of existing treatments is a clinical priority. Astaxanthin (AST) is a potent antioxidant carotenoid with an established safety profile that is approved as a dietary supplement. AST has been reported to act as a chemopreventive agent limiting the initiation and establishment of tumors. We are investigating the hypothesis that AST sensitizes breast cancer cells to standard chemotherapy drugs and ionizing radiation (IR) used to treat breast cancer. We found that treatment with either an AST-rich algal extract supplement (L-10) or a synthetic 3S, 3's AST isomer (‘sAST’) alone did not significantly alter proliferation of immortalized MCF10A mammary epithelial cells or seven out of eight breast cancer cell lines, while L-10 decreased clonogenic growth of four out of five breast cancer cell lines tested so far. We next evaluated whether AST altered response to IR. We found that while AST neither sensitizes nor protects MCF10A cells, no radiosensitization was observed in the four breast cancer cell lines tested thus far. In the BT549 cell line, AST showed slight antagonism of IR response; however, the combination of IR and AST still results in fewer overall colonies than either treatment modality alone. We next investigated whether AST can synergize with chemotherapy drugs in vitro. While AST pretreatment does not increase the toxicity of Doxorubicin (Dox) or 5-fluorouracil (5-FU) on MCF10A cells, MDA-MB-231 and 4T1 cancer cells pretreated with L-10 demonstrate an augmented response to Dox, 5-FU, and methotrexate. Mechanistically, we have determined that cell lines demonstrating AST-mediated sensitization exhibit a decrease in constitutive phosphorylation of Akt, whereas Akt phosphorylation was not affected in unresponsive cell lines. However, overexpression of myristoylated Akt did not reverse the observed sensitization, suggesting involvement of different signaling pathways in sensitization by AST. Responding cancer cell lines also show decreases in NFκB and/or STAT3 phosphorylation following AST treatment. We are currently evaluating whether decreased activation of these pathways plays a role in AST-mediated chemosensitization. Identification of the molecular determinants of AST sensitivity may allow for the identification of patient populations whose treatment regimens may benefit from AST supplementation (Supported by DoD W81XWH-09-1-0067). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3728. doi:1538-7445.AM2012-3728