SH003 represses tumor angiogenesis by blocking VEGF binding to VEGFR2.
Tumor angiogenesis is a key feature of cancer progression, because a tumor requires abundant oxygen and nutrition to grow. Here, we demonstrate that SH003, a mixed herbal extract containing Astragalus membranaceus (Am), Angelica gigas (Ag) and Trichosanthes Kirilowii Maximowicz (Tk), represses VEGF-induced tumor angiogenesis both in vitro and in vivo. SH003 inhibited VEGF-induced migration, invasion and tube formation in human umbilical vein endothelial cells (HUVEC) with no effect on the proliferation. SH003 reduced CD31-positive vessel numbers in tumor tissues and retarded tumor growth in our xenograft mouse tumor model, while SH003 did not affect pancreatic tumor cell viability. Consistently, SH003 inhibited VEGF-stimulated vascular permeability in ears and back skins. Moreover, SH003 inhibited VEGF-induced VEGFR2-dependent signaling by blocking VEGF binding to VEGFR2. Therefore, our data conclude that SH003 represses tumor angiogenesis by inhibiting VEGF-induced VEGFR2 activation, and suggest that SH003 may be useful for treating cancer.
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Korea.
Hyeong Sim
HS
Choi
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Korea.
Min Kyoung
MK
Kim
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Korea.
Kangwook
K
Lee
Department of Science in Korean Medicine, Graduate School, Kyung Hee University, Seoul, Korea.
Kang Min
KM
Lee
Jeju International Marine Science Center for Research and Education, Korea Institute of Ocean Science & Technology (KIOST), Jeju, Korea.
Youn Kyung
YK
Choi
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Korea.
Yong Cheol
YC
Shin
Department of Biotechnology, Korea National University of Transportation, Jeungpyeong, Chungbuk, Korea.
Sung-Gook
SG
Cho
Department of Preventive Medicine, College of Korean Medicine, Kyung Hee University, Seoul, Korea.
Seong-Gyu
SG
Ko
D029969:Angelica; D000818:Animals; D027883:Astragalus Plant; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D011897:Random Allocation; D015398:Signal Transduction; D029778:Trichosanthes; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D010936:Plant Extracts; C000613735:SH003 extract; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
SH003; TCM; VEGF; VEGFR2; tumor angiogenesis