Hedyotis diffusa Willd extract suppresses Sonic hedgehog signaling leading to the inhibition of colorectal cancer angiogenesis

• Published in: International journal of oncology Vol. 42; no. 2; pp. 651 - 656
• Main Authors: LIN, JIUMAO, WEI, LIHUI, SHEN, ALING, CAI, QIAOYAN, XU, WEI, LI, HUANG, ZHAN, YOUZHI, HONG, ZHENFENG, PENG, JUN
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-02-2013; Spandidos Publications UK Ltd
• Subjects: Angiogenesis; Animals; Apoptosis - drug effects; Cancer therapies; Cell Line, Tumor; Cell Proliferation - drug effects; Chemotherapy; Chinese medicine; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - genetics; Colorectal Neoplasms - pathology; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - adverse effects; Drugs, Chinese Herbal - chemistry; Ethanol; Gene Expression Regulation, Neoplastic - drug effects; Hedgehog Proteins - antagonists & inhibitors; Hedgehog Proteins - genetics; Hedyotis - chemistry; Hedyotis diffusa Willd; Humans; Kinases; Laboratory animals; Medical research; Mice; Natural products; Neovascularization, Pathologic - drug therapy; Penicillin; Protein expression; Proteins; Rodents; Signal Transduction - drug effects; sonic hedgehog signal pathway; STAT3 Transcription Factor - metabolism; Studies; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Xenograft Model Antitumor Assays; United States > US; China
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2012.1753

Sonic hedgehog (SHH) signaling pathway promotes the process of angiogenesis, contributing to the growth and progression of many human malignancies including colorectal cancer (CRC), which therefore has become a promising target for cancer chemotherapy. Hedyotis diffusa Willd (HDW), as a well-known traditional Chinese herbal medicine, has long been used in China for the clinic treatment of various cancers. Recently, we reported that HDW can inhibit colorectal cancer growth in vivo and in vitro via suppression of the STAT3 pathway. In addition, we demonstrated the anti-angiogenic activity of HDW in vitro. To further elucidate the mechanism of the tumoricidal activity of HDW, by using a CRC mouse xenograft model we evaluated the in vivo effect of the ethanol extract of HDW (EEHDW) on tumor angiogenesis, and investigated the underlying molecular mechanisms. We found that EEHDW could significantly reduce intratumoral microvessel density (MVD), indicating its activity of antitumor angiogenesis in vivo. EEHDW suppressed the activation of SHH signaling in CRC xenograft tumors since it significantly decreased the expression of key mediators of SHH pathway. EEHDW treatment inhibited the expression of the critical SHH signaling target gene VEGF-A as well as its specific receptor VEGFR2. Taken together, we propose for the first time that Hedyotis diffusa Willd inhibits colorectal cancer growth in vivo via inhibition of SHH-mediated tumor angiogenesis.