title: Targeting sonic hedgehog signaling by compounds and derivatives from natural products.
abstract: Cancer stem cells (CSCs) are a major cause of cancer treatment failure, relapse, and drug resistance and are known to be responsible for cancer cell invasion and metastasis. The Sonic hedgehog (Shh) signaling pathway is crucial to embryonic development. Intriguingly, the aberrant activation of the Shh pathway plays critical roles in developing CSCs and leads to angiogenesis, migration, invasion, and metastasis. Natural compounds and chemical structure modified derivatives from complementary and alternative medicine have received increasing attention as cancer chemopreventives, and their antitumor effects have been demonstrated both in vitro and in vivo. However, reports for their bioactivity against CSCs and specifically targeting Shh signaling remain limited. In this review, we summarize investigations of the compounds cyclopamine, curcumin, epigallocatechin-3-gallate, genistein, resveratrol, zerumbone, norcantharidin, and arsenic trioxide, with a focus on Shh signaling blockade. Given that Shh signaling antagonism has been clinically proven as effective strategy against CSCs, this review may be exploitable for development of novel anticancer agents from complementary and alternative medicine.
authors.affiliation: School of Chinese Medicine, China Medical University, Taichung 404, Taiwan ; Graduate Institute of Biostatistics, China Medical University, Taichung 404, Taiwan ; Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan.
authors.forename: Yu-Chuen
authors.initials: YC
authors.lastname: Huang
authors.forename: K S Clifford
authors.initials: KS
authors.lastname: Chao
authors.forename: Hui-Fen
authors.initials: HF
authors.lastname: Liao
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen