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.
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Authors | Yu Wang, Yan Zhao, Ying Liu, Linli Tian, Dejun Jin |
Journal | Molecules (Basel, Switzerland)
(Molecules)
Vol. 16
Issue 10
Pg. 8152-64
(Sep 27 2011)
ISSN: 1420-3049 [Electronic] Switzerland |
PMID | 21952497
(Publication Type: Journal Article)
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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
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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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