title: Chamaejasmine inactivates Akt to trigger apoptosis in human HEp-2 larynx carcinoma cells.
abstract: In the present study, we investigated the mechanisms of chamaejasmine action on human HEp-2 larynx carcinoma cells, which possess constitutively active Akt. Results indicated that chamaejasmine showed more notable anticancer activity than apigenin against HEp-2, PC-3, NCI-H1975, HT-29 and SKOV-3. Moreover, chamaejasmine presented most significantly inhibition towards HEp-2, with IC₅₀ values of 1.92 µM. Treatment of HEp-2 cells with chamaejasmine (1-4 μM) resulted in signiﬁcant dose-dependent decrease in Akt phosphorylation at Serine473. Chamaejasmine-mediated dephosphorylation of Akt resulted in inhibition of its kinase activity, which was conﬁrmed by reduced phosphorylation of proapoptotic proteins BAD and glycogen synthase kinase-3, essential downstream targets of Akt. Inactivation of Akt seems to be associated with downregulation of insulin-like growth factor receptor 1 protein level and inhibition of its autophosphorylation upon chamaejasmine treatment. Exposure to chamaejasmine signiﬁcantly induced caspase-9 and caspase-3 activity. In vivo, chamaejasmine intake through gavage resulted in inactivation of Akt and induction of apoptosis in HEp-2 tumors. These results suggest that Akt inactivation and dephosphorylation of BAD is a critical event, at least in part, in chamaejasmine-induced HEp-2 cells apoptosis.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Linli
authors.initials: L
authors.lastname: Tian
authors.forename: Dejun
authors.initials: D
authors.lastname: Jin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D044946:Biflavonoids / Q000494:pharmacology*; D053148:Caspase 3 / Q000096:biosynthesis / Q000378:metabolism; D053453:Caspase 9 / Q000096:biosynthesis / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007822:Laryngeal Neoplasms; D051379:Mice; D008819:Mice, Nude; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051025:bcl-Associated Death Protein / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C494819:BAD protein, human; D044946:Biflavonoids; D051025:bcl-Associated Death Protein; C511440:chamaejasmine; D047310:Apigenin; D058539:Phosphatidylinositol 3-Kinase; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D053148:Caspase 3; D053453:Caspase 9