| Kinase Assay: |
| Molecules. 2011 Sep 27;16(10):8152-64. | | Chamaejasmine inactivates Akt to trigger apoptosis in human HEp-2 larynx carcinoma cells.[Pubmed: 21952497] | In the present study, we investigated the mechanisms of Chamaejasmine action on human HEp-2 larynx carcinoma cells, which possess constitutively active Akt.
METHODS AND RESULTS:
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.
CONCLUSIONS:
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. | | Molecules. 2011 Sep 27;16(10):8165-80. | | Chamaejasmine induces apoptosis in human lung adenocarcinoma A549 cells through a Ros-mediated mitochondrial pathway.[Pubmed: 21952498 ] | In the present study, the anticancer activity of Chamaejasmine towards A549 human lung adenocarcinoma cells was investigated.
METHODS AND RESULTS:
In order to explore the underlying mechanism of cell growth inhibition of Chamaejasmine, cell cycle distribution, ROS generation, mitochondrial membrane potential (Δψ(m)) disruption, and expression of cytochrome c, Bax, Bcl-2, caspase-3, caspase-9 and PARP were measured in A549 cells. Chamaejasmine inhibited the growth of A549 cells in a time and dose-dependent manner. The IC₅₀ value was 7.72 µM after 72 h treatment. Chamaejasmine arrested the cell cycle in the G2/M phase and induced apoptosis via a ROS-mediated mitochondria-dependent pathway. Western blot analysis showed that Chamaejasmine inhibited Bcl-2 expression and induced Bax expression to desintegrate the outer mitochondrial membrane and causing cytochrome c release. Mitochondrial cytochrome c release was associated with the activation of caspase-9 and caspase-3 cascade, and active-caspase-3 was involved in PARP cleavage.
CONCLUSIONS:
All of these signal transduction pathways are involved in initiating apoptosis. To the best of our knowledge, this is the first report demonstrating the cytotoxic activity of Chamaejasmine towards A549 in vitro. |
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