Abstract 1614: Coconut kernel extract as a novel chemopreventive agent that target cancer stemness

Abstract

Cancer stemness can be defined as integrated molecular programs that confer stem cell phenotype to cancer cells. Cancer stemness is associated with drug resistance, immune evasion and metastasis. Our ongoing work indicates that oncogene MYC may enhance cancer stemness. We are interested to identify novel dietary agents that can target MYC mediated cancer stemness pathway. Coconut (Cocos nucifera L.) kernel extract (CKE) is traditionally used in tradition Indian medicine as anti-inflammatory diet. Here, we have investigated the potential CKE mediated targeting of MYC mediated skin carcinogenesis. Methods: To determine tumor-suppressing activity of isolated CKE in vivo, we used a DMBA/TPA-mediated skin cancer in Balb/c mice. C-MYC expression in skin tumor was studied by immuno-histochemistry. The bioactive component of CKE was studied by performing histopathology and immunohistochemistry. Results: CKE treatment decreased DMBA/TPA induced tumorigenicity by 200-fold (p<0.001, n=10). Histological and Immuno histo-chemistry studies suggested that CKE treatment significantly inhibited over expression of c-Myc protein on skin tumorigenesis induced by DMBA/TPA. Additionally, CKE treatment also shows significant inhibitory effect on lipid peroxidase and stimulatory effect on glutathione, catalase and superoxide dismutase activities in tissues treated with DMBA/TPA. Additionally, in vitro study showed that CKE reduces DMBA/TPA induced stemness in skin keratinocytes. CKE contains lauric acid as per analysis performed by high performance liquid chromatography and Nuclear magnetic resonance. However, purified lauric acid alone did not exhibit potent anti-stemness activity in vitro as compared to CKE. Conclusions: These findings demonstrate that CKE is a tumor suppressing agent for chemically induced skin cancer. CKE prevent DMBA/TPA induced oxidative stress and potentially act as an inhibitor of MYC-induced cancer stemness. Citation Format: Sandhya Sorra, Joyeeta Talukdar, Gayatri Gogoi, Hong Li, Debabrat Baishya, Bikul Das. Coconut kernel extract as a novel chemopreventive agent that target cancer stemness [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 1614.