Neoalbaconol inhibits angiogenesis and tumor growth by suppressing EGFR-mediated VEGF production.

Abstract

Neoalbaconol, derived from Albatrellus confluens, shows anti-cancer activities in the previously study, but its role in angiogenesis is unknown. Here, we determined whether neoalbaconol could attenuate angiogenesis and how does it occur. Data demonstrated that neoalbaconol could inhibit the proliferation of breast cancer cells and induce apoptosis. Also, neoalbaconol suppressed vascular endothelial growth factor (VEGF)-induced human umbilical vascular endothelial cells (HUVECs) proliferation, migration, invasion, and capillary-like tube formation in vitro and reduced tumor angiogenesis in vivo. VEGF receptor activation and the downstream signal transduction cascades activation were inhibited by neoalbaconol. Additionally, neoalbaconol blocked EGFR-mediated VEGF production. EGFR overexpression reversed the neoalbaconol-induced VEGF reduction, confirming the importance of the EGFR inhibition in anti-angiogenesis of neoalbaconol. Furthermore, neoalbaconol inhibited tumor growth and tumor angiogenesis in a breast cancer xenograft model in vivo. Taken together, these results indicate that neoalbaconol could inhibit tumor angiogenesis and growth through direct suppression effects on vascular endothelial cells and reduction of proangiogenic factors in cancer cells.

• Authors: Xinfang Yu, Wei Li, Qipan Deng, Shuo You, Haidan Liu, Songling Peng, Xiaolan Liu, Jingchen Lu, Xiangjian Luo, Lifang Yang, Min Tang, Xinxian Weng, Wei Yi, Wenbin Liu, Shengqi Wu, Zhihui Ding, Tao Feng, Jian Zhou, Jia Fan, Ann M Bode, Zigang Dong, Jikai Liu, Ya Cao
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 56 Issue 5 Pg. 1414-1426 (05 2017) ISSN: 1098-2744 [Electronic] United States
• PMID: 27996164 (Publication Type: Journal Article)
• Copyright: © 2017 Wiley Periodicals, Inc.

Chemical References

• Antineoplastic Agents
• Sesquiterpenes
• VEGFA protein, human
• Vascular Endothelial Growth Factor A
• neoalbaconol
• EGFR protein, human
• ErbB Receptors

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (blood supply, drug therapy, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• ErbB Receptors (genetics, metabolism)
• Female
• Human Umbilical Vein Endothelial Cells (drug effects)
• Humans
• Mice, Nude
• Neovascularization, Pathologic (drug therapy, metabolism)
• Sesquiterpenes (pharmacology)
• Vascular Endothelial Growth Factor A (metabolism)
• Xenograft Model Antitumor Assays