Angiogenesis plays a critical role in the development of solid tumors by 
supplying nutrients and oxygen to support continuous growth of tumor as well as 
providing an avenue for hematogenous metastasis. Tumor angiogenesis is highly 
regulated by multiple intracellular signaling transduction cascades such as 
Hedgehog, STAT3, Akt and p70S6K pathways that are known to malfunction in many 
types of cancer including colorectal cancer (CRC). Therefore, suppression of 
tumor angiogenesis through targeting these signaling pathways has become a 
promising strategy for cancer chemotherapy. Ursolic acid (UA) is a major active 
compound present in many medicinal herbs that have long been used in China for 
the clinical treatment of various types of cancer. Although previous studies 
have demonstrated an antitumor effect for UA, the precise mechanisms of its 
anti-angiogenic activity are not well understood. To further elucidate the 
mechanism(s) of the tumorcidal activity of UA, using a CRC mouse xenograft 
model, chick embryo chorioallantoic membrane (CAM) model, the human colon 
carcinoma cell line HT-29 and human umbilical vein endothelial cells (HUVECs), 
in the present study we evaluated the efficacy of UA against tumor growth and 
angiogenesis in vivo and in vitro and investigated the underlying molecular 
mechanisms. We found that administration of UA significantly inhibited tumor 
volume but had no effect on body weight changes in CRC mice, suggesting that UA 
can suppress colon cancer growth in vivo without noticeable signs of toxicity. 
In addition, UA treatment reduced intratumoral microvessel density (MVD) in CRC 
mice, decreased the total number of blood vessels in the CAM model, and dose and 
time-dependently inhibited the proliferation, migration and tube formation of 
HUVECs, demonstrating UA's antitumor angiogenesis in vivo and in vitro. 
Moreover, UA treatment inhibited the expression of critical angiogenic factors, 
such as VEGF-A and bFGF. Furthermore, UA suppressed the activation of sonic 
hedgehog (SHH), STAT3, Akt and p70S6K pathways. Collectively, our findings 
suggest that inhibition of tumor angiogenesis via suppression of multiple 
signaling pathways might be one of the mechanisms whereby UA can be effective in 
cancer treatment.