Chamaejasmine

Apoptosis induced by chamaejasmine in human osteosarcoma cells through p53 pathway.[Pubmed:25677904]

Tumour Biol. 2015 Jul;36(7):5433-9.

Osteosarcoma cancer is one of the most lethal malignancies, and there is no effective preventive measure to date. Chamaejasmine is the major ingredient in Stellera chamaejasme L. Except its potent pain-relieving efficacy as reported, Chamaejasmine also exerted its anti-tumor activity in several tumor models. Here, we reported that Chamaejasmine had a profound anti-proliferative effect on human osteosarcoma cells in a concentration-dependent and time-dependent manner, which was associated with an increase of p21 and bax and a decrease of bcl-2 and consequently increased caspase-3 activity. The main mechanism of anti-tumor potency was mainly attributed to the induction of p53. Chamaejasmine hugely elevated the expression of p53. The results of p53 shRNA experiment further demonstrated that p53 knockdown severely impaired the sensitivity of tested cells to Chamaejasmine, implicating the important role of p53 played in Chamaejasmine's anti-tumor activity. In conclusion, results showed Chamaejasmine induced apoptosis in MG63 cells and could be a candidate drug for osteosarcoma cancer chemoprevention.

Chamaejasmine inactivates Akt to trigger apoptosis in human HEp-2 larynx carcinoma cells.[Pubmed:21952497]

Molecules. 2011 Sep 27;16(10):8152-64.

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 IC(5)(0) values of 1.92 microM. Treatment of HEp-2 cells with Chamaejasmine (1-4 muM) resulted in signi fi cant dose-dependent decrease in Akt phosphorylation at Serine473. Chamaejasmine-mediated dephosphorylation of Akt resulted in inhibition of its kinase activity, which was con fi rmed 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 signi fi cantly 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.

Chamaejasmine induces apoptosis in human lung adenocarcinoma A549 cells through a Ros-mediated mitochondrial pathway.[Pubmed:21952498]

Molecules. 2011 Sep 27;16(10):8165-80.

In the present study, the anticancer activity of Chamaejasmine towards A549 human lung adenocarcinoma cells was investigated. In order to explore the underlying mechanism of cell growth inhibition of Chamaejasmine, cell cycle distribution, ROS generation, mitochondrial membrane potential (Deltapsi(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 IC(5)(0) value was 7.72 microM 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. 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.

Chamaejasmine arrests cell cycle, induces apoptosis and inhibits nuclear NF-kappaB translocation in the human breast cancer cell line MDA-MB-231.[Pubmed:23344197]

Molecules. 2013 Jan 11;18(1):845-58.

In this study, the anticancer activity of Chamaejasmine was characterized in the human breast cancer cell line, MDA-MB-231. Cell viability and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Western blotting was performed to determine changes in levels of various proteins. Results showed that treatment with Chamaejasmine (4-16 muM) inhibited cell proliferation, which correlated with G2/M phase arrest and apoptosis in MDA-MB-231 cells. Chamaejasmine treatment of MDA-MB-231 cells resulted in induction of WAF1/p21 and KIP1/p27, decrease in cyclins A and cyclins B1. Cyclin-dependent kinase (cdk) 2 and cdc2 was also decreased after Chamaejasmine treatment. Moreover, inhibition of nuclear translocation, phosphorylation of NF-kappaB, activation of IKKalpha and IKKbeta, inhibition of phosphorylation and degradation of IkappaBalpha were also detected in this work. Our findings suggested that Chamaejasmine could be explored as a preventive and perhaps as a chemotherapeutic agent in the management of breast cancer.