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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) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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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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