The Ashitaba (Angelica keiskei) Chalcones 4-hydroxyderricin and xanthoangelol suppress melanomagenesis by targeting BRAF and PI3K

Tianshun Zhang, Qiushi Wang, Mangaladoss Fredimoses, Ge Gao, Keke Wang, Hanyong Chen, Ting Wang, Naomi Oi, Tatyana A. Zykova, Kanamata Reddy, Ke Yao, Weiya Ma, Xiaoyu Chang, Mee Hyun Lee, Moeez Ghani Rathore, Ann M. Bode, Hitoshi Ashida, Scott M. Lippman, Zigang Dong

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)607-619
Number of pages13
JournalCancer Prevention Research
Volume11
Issue number10
DOIs
StatePublished - Oct 2018

Bibliographical note

Funding Information:
The authors thank Tara Adams for supporting animal experiments, Todd Schuster for supporting experiments and Dr. Tia Rai for assistance in submitting this manuscript (The Hormel Institute, University of Minnesota, Austin, MN). This work was supported by The Hormel Foundation, NIH grants CA166011, CA187027, and CA196639 (to Z. Dong) and a National Natural Science Foundation of China, "Foreign Young Scientist" grant, NSFC81650110530 (to M. Fredimoses).

Publisher Copyright:
© 2018 American Association for Cancer Research.

PubMed: MeSH publication types

  • Journal Article
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

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