Chamaejasmine Inactivates Akt To Trigger Apoptosis in Human HEp-2 Larynx Carcinoma Cells
AbstractIn 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.
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Wang, Y.; Zhao, Y.; Liu, Y.; Tian, L.; Jin, D. Chamaejasmine Inactivates Akt To Trigger Apoptosis in Human HEp-2 Larynx Carcinoma Cells. Molecules 2011, 16, 8152-8164.
Wang Y, Zhao Y, Liu Y, Tian L, Jin D. Chamaejasmine Inactivates Akt To Trigger Apoptosis in Human HEp-2 Larynx Carcinoma Cells. Molecules. 2011; 16(10):8152-8164.Chicago/Turabian Style
Wang, Yu; Zhao, Yan; Liu, Ying; Tian, Linli; Jin, Dejun. 2011. "Chamaejasmine Inactivates Akt To Trigger Apoptosis in Human HEp-2 Larynx Carcinoma Cells." Molecules 16, no. 10: 8152-8164.