TY - JOUR
T1 - The Ashitaba (Angelica keiskei) Chalcones 4-hydroxyderricin and xanthoangelol suppress melanomagenesis by targeting BRAF and PI3K
AU - Zhang, Tianshun
AU - Wang, Qiushi
AU - Fredimoses, Mangaladoss
AU - Gao, Ge
AU - Wang, Keke
AU - Chen, Hanyong
AU - Wang, Ting
AU - Oi, Naomi
AU - Zykova, Tatyana A.
AU - Reddy, Kanamata
AU - Yao, Ke
AU - Ma, Weiya
AU - Chang, Xiaoyu
AU - Lee, Mee Hyun
AU - Rathore, Moeez Ghani
AU - Bode, Ann M.
AU - Ashida, Hitoshi
AU - Lippman, Scott M.
AU - Dong, Zigang
N1 - Publisher Copyright:
© 2018 American Association for Cancer Research.
PY - 2018/10
Y1 - 2018/10
N2 - Malignant melanoma is an aggressive tumor of the skin and still lacks effective preventive and therapeutic treatments. In melanoma, both the BRAF/MEK/ERK and PI3-K/AKT signaling pathways are constitutively activated through multiple mechanisms, which result in cell-cycle progression and prevention of apoptosis. Therefore, the development of novel strategies for targeting BRAF and PI3K are of utmost importance. In this study, we found that Ashitaba (Angelica keiskei) chalcones, 4-hydroxyderricin (4HD) and xanthoangelol (XAG), suppressed melanoma development by directly targeting both BRAFV600E and PI3K, 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 or 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 PI3K, providing hope for rapid clinical translation.
AB - Malignant melanoma is an aggressive tumor of the skin and still lacks effective preventive and therapeutic treatments. In melanoma, both the BRAF/MEK/ERK and PI3-K/AKT signaling pathways are constitutively activated through multiple mechanisms, which result in cell-cycle progression and prevention of apoptosis. Therefore, the development of novel strategies for targeting BRAF and PI3K are of utmost importance. In this study, we found that Ashitaba (Angelica keiskei) chalcones, 4-hydroxyderricin (4HD) and xanthoangelol (XAG), suppressed melanoma development by directly targeting both BRAFV600E and PI3K, 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 or 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 PI3K, providing hope for rapid clinical translation.
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U2 - 10.1158/1940-6207.CAPR-18-0092
DO - 10.1158/1940-6207.CAPR-18-0092
M3 - Article
C2 - 29980517
AN - SCOPUS:85054349078
SN - 1940-6207
VL - 11
SP - 607
EP - 619
JO - Cancer Prevention Research
JF - Cancer Prevention Research
IS - 10
ER -