title: Nicotinic acetylcholine receptor-based blockade: applications of molecular targets for cancer therapy.
abstract: The nicotinic acetylcholine receptor (nAChR) was first characterized in 1970 as a membrane receptor of a neurotransmitter and an ion channel. nAChRs have been shown to be involved in smoking-induced cancer formation in multiple types of human cancer cells. In vitro and in vivo animal studies have shown that homopentameric nAChR inhibitors, such as methyllycaconitine and α-Bgtx, can attenuate nicotine-induced proliferative, angiogenic, and metastatic effects in lung, colon, and bladder cancer cells. Recent publications have shown that α9-nAChR is important for breast cancer formation, and in many in vivo studies, α9-nAChR-specific antagonists (e.g., α-ImI, α-ImI, Vc1.1, RgIA, and It14a) produced an analgesic effect. Vc1.1 functions in a variety of animal pain models and currently has entered phase II clinical trials. For cancer therapy, natural compounds such as garcinol and EGCG have been found to block nicotine- and estrogen-induced breast cancer cell proliferation through inhibition of the α9-nAChR signaling pathway. A detailed investigation of the carcinogenic effects of nAChRs and their specific antagonists would enhance our understanding of their value as targets for clinical translation.
authors: Department of Surgery, School of Medicine, and Graduate Institute of Medical Sciences, College of Medicine, Taipei, Taiwan.
authors: Chih-Hsiung
authors: CH
authors: Wu
authors: Chia-Hwa
authors: CH
authors: Lee
authors: Yuan-Soon
authors: YS
authors: Ho
mesh_terms: D000157:Aconitine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016588:Anticarcinogenic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000378:metabolism* / Q000628:therapy*; D018733:Nicotinic Antagonists / Q000627:therapeutic use*; D011978:Receptors, Nicotinic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012907:Smoking / Q000009:adverse effects; D013729:Terpenes / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016588:Anticarcinogenic Agents; C498540:CHRNA9 protein, human; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D013729:Terpenes; C054634:methyllycaconitine; D002392:Catechin; C045651:epigallocatechin gallate; C054597:garcinol; D000157:Aconitine