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

doi:10.1158/1940-6207.CAPR-18-0092

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

The Hormel Institute

Research output: Contribution to journal › Article › peer-review

10 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 language	English (US)
Pages (from-to)	607-619
Number of pages	13
Journal	Cancer Prevention Research
Volume	11
Issue number	10
DOIs	https://doi.org/10.1158/1940-6207.CAPR-18-0092
State	Published - 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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1158/1940-6207.CAPR-18-0092

Find It

Find It at U of M Libraries

Cite this

Zhang, T., Wang, Q., Fredimoses, M., Gao, G., Wang, K., Chen, H., Wang, T., Oi, N., Zykova, T. A., Reddy, K., Yao, K., Ma, W., Chang, X., Lee, M. H., Rathore, M. G., Bode, A. M., Ashida, H., Lippman, S. M., & Dong, Z. (2018). The Ashitaba (Angelica keiskei) Chalcones 4-hydroxyderricin and xanthoangelol suppress melanomagenesis by targeting BRAF and PI3K. Cancer Prevention Research, 11(10), 607-619. https://doi.org/10.1158/1940-6207.CAPR-18-0092

Zhang, T , Wang, Q, Fredimoses, M, Gao, G, Wang, K, Chen, H, Wang, T, Oi, N, Zykova, TA, Reddy, K, Yao, K, Ma, W, Chang, X, Lee, MH, Rathore, MG, Bode, AM, Ashida, H, Lippman, SM & Dong, Z 2018, 'The Ashitaba (Angelica keiskei) Chalcones 4-hydroxyderricin and xanthoangelol suppress melanomagenesis by targeting BRAF and PI3K', Cancer Prevention Research, vol. 11, no. 10, pp. 607-619. https://doi.org/10.1158/1940-6207.CAPR-18-0092

@article{684cc7c13835461780eff78e72b82dc9,

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

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.",

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

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: {\textcopyright} 2018 American Association for Cancer Research.",

year = "2018",

month = oct,

doi = "10.1158/1940-6207.CAPR-18-0092",

language = "English (US)",

volume = "11",

pages = "607--619",

journal = "Cancer Prevention Research",

issn = "1940-6207",

publisher = "American Association for Cancer Research Inc.",

number = "10",

}

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 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85054349078&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054349078&partnerID=8YFLogxK

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 -

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

Abstract

Bibliographical note

PubMed: MeSH publication types

UN SDGs

Publisher link

Find It

Other files and links

Fingerprint

Cite this