Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P42574 (caspase-3)
 45,978 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deltonin, a steroidal saponin, isolated from Dioscorea zingiberensis Wright (DZW), has shown high-cytotoxic activity in cancer cells. However, its mechanisms and in vivo anti-cancer effects remain unknown. In the present study, we evaluated the effects and explored the anti-tumor mechanisms of deltonin on a panel of colon cancer cell lines and in a mouse model of murine colon cancer C26. Deltonin had more cytotoxic effect on C26 cells than 5-fluorouracil had, promoting dramatic G2-M phase arrest and apoptosis in C26 cells in a concentration-dependent manner; oral administration of deltonin significantly inhibited the tumor growth and prolonged survival of the tumor bearing mice. The deltonin treatment caused a noticeable apoptosis in tumor tissue, which associated with increased levels of Bax, activated caspase-3, caspase-9, and cleaved poly (ADPribose) polymerase, decreased pro-caspase-8, pro-caspase-9, Bcl-2 expression levels and extracellular signal-regulated kinase-1/2 activity; and dose-dependently inhibit angiogenesis. In conclusion, the findings in this study demonstrated that deltonin is an effective natural agent for cancer therapy, which may be mediated, in part, by induction of apoptosis, as well as involve mitogen-activated protein kinase pathways, and inhibition of angiogenesis.
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PMID:Deltonin, a steroidal saponin, inhibits colon cancer cell growth in vitro and tumor growth in vivo via induction of apoptosis and antiangiogenesis. 2147 12

Deltonin is an active component purified from Dioscorea zingiberensis WRIGHT (DZW), and has shown anticancer effects. However, its mechanism of action remains elusive. In the present study, we investigated the effect of Deltonin on a panel of cancer cell lines and analyzed its mechanism in C26 cells, a murine colon carcinoma cell. Our results showed that Deltonin markedly inhibited the growth of all examined cancer cell lines. Deltonin induced dose- and time-dependent apoptosis in C26 cells. The event of apoptosis was accompanied by the release of cytochrome c, depolarization of mitochondrial membrane potential, and dose- and time-dependent reactive oxygen species (ROS) generation. Deltonin also increased the expression of Bax, decreased the expression of B-cell lymphoma/lewkmia-2 (Bcl-2), and induced the activation of caspase 9, caspase 3 and poly(ADP-ribose) polymerase (PARP). Furthermore, Deltonin decreased Akt and extracellular signal-regulated kinase-1/2 (ERK(1/2)) activity. These results demonstrate that Deltonin mediates the growth inhibition of cancer cells through multiple targets, which include the generation of reactive oxygen species (ROS), mitochondrial apoptosis and the inhibition of the mitogen-activated protein kinase (MAPK) and Akt signaling pathways, suggesting Deltonin is a potent cancer preventive and therapeutic agent.
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PMID:Deltonin isolated from Dioscorea zingiberensis inhibits cancer cell growth through inducing mitochondrial apoptosis and suppressing Akt and mitogen activated protein kinase signals. 2180 11