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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.
AuthorsYu Wang, Yan Zhao, Ying Liu, Linli Tian, Dejun Jin
JournalMolecules (Basel, Switzerland) (Molecules) Vol. 16 Issue 10 Pg. 8152-64 (Sep 27 2011) ISSN: 1420-3049 [Electronic] Switzerland
PMID21952497 (Publication Type: Journal Article)
Chemical References
  • Antineoplastic Agents, Phytogenic
  • BAD protein, human
  • Biflavonoids
  • bcl-Associated Death Protein
  • chamaejasmine
  • Apigenin
  • Phosphatidylinositol 3-Kinase
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt
  • Glycogen Synthase Kinase 3
  • Caspase 3
  • Caspase 9
Topics
  • Animals
  • Antineoplastic Agents, Phytogenic (pharmacology)
  • Apigenin (pharmacology)
  • Apoptosis (drug effects)
  • Biflavonoids (pharmacology)
  • Caspase 3 (biosynthesis, metabolism)
  • Caspase 9 (biosynthesis, metabolism)
  • Cell Line, Tumor
  • Cell Survival (drug effects)
  • Female
  • Glycogen Synthase Kinase 3 (metabolism)
  • HEK293 Cells
  • Humans
  • Laryngeal Neoplasms
  • Mice
  • Mice, Nude
  • Phosphatidylinositol 3-Kinase (metabolism)
  • Phosphorylation (drug effects)
  • Proto-Oncogene Proteins c-akt (antagonists & inhibitors, metabolism)
  • Receptor, IGF Type 1 (biosynthesis, metabolism)
  • Signal Transduction (drug effects)
  • bcl-Associated Death Protein (metabolism)

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