Abstract 4798: The Ashitaba (Angelica keiskei) chalcones 4-hydroxyderricin and xanthoangelol suppress melanomagenesis by targeting BRAF and PI3-K

Abstract

Abstract Malignant melanoma is an aggressive tumor of the skin and still lacks effective preventive and therapeutic approaches. In melanoma, both the BRAF/MEK/ERK and PI3-K/AKT signaling pathways are constitutively activated though multiple mechanisms, which result in cell cycle progression and prevention of apoptosis. Therefore, the development of novel strategies for targeting BRAF and PI3-K are of utmost importance. In the current study, we found that the Ashitaba (Angelica keiskei) chalcones, 4-hydroxyderricin (4HD) and xanthoangelol (XAG), suppressed melanoma carcinogenesis by directly targeting both BRAFV600E and PI3-K, which blocked the activation of downstream signaling. This led to the induction of G1 phase cell cycle arrest and apoptosis in melanoma cells. Importantly, 4HD and XAG dramatically attenuated tumor incidence and volume in the BRAF-activated Pten-deficient melanoma mouse model. Our findings suggest that 4HD and XAG are promising chemopreventive or potential therapeutic agents against melanomagenesis that act by targeting both BRAF and PI3-K, providing hope for rapid clinical translation. Citation Format: Tianshun Zhang, Qiushi Wang, Hitoshi Ashida, Ann Bode, Zigang Dong. The Ashitaba (Angelica keiskei) chalcones 4-hydroxyderricin and xanthoangelol suppress melanomagenesis by targeting BRAF and PI3-K [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 4798.