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Molecules 2011, 16(10), 8152-8164; doi:10.3390/molecules16108152

Chamaejasmine Inactivates Akt To Trigger Apoptosis in Human HEp-2 Larynx Carcinoma Cells

1 Department of Otorhinolaryngology–Head and Neck Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin 150001, China 2 Department of Otorhinolaryngology, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, China
* Author to whom correspondence should be addressed.
Received: 1 September 2011 / Revised: 16 September 2011 / Accepted: 19 September 2011 / Published: 27 September 2011
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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.
Keywords: chamaejasmine; HEp-2; Akt; in vivo; apoptosis chamaejasmine; HEp-2; Akt; in vivo; apoptosis
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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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.

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