Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cepharanthin (CEP) is a biscoclaurine alkaloid extracted from Stephania cepharantha Hayata. CEP is reported to inhibit drug resistance by inhibiting P-glycoprotein, a drug efflux pump, and recently to induce apoptosis. In the present study, we examined the effects of CEP as an inhibitor of adriamycin (ADR) resistance on ADR-induced apoptosis and necrosis. First, we established p53-deficient ADR-resistant osteosarcoma cell lines, SaOS2-AR and SaOS2 F-AR. Resistant cells showed a higher level of intracellular glutathione peroxidase activity than parent cells. P-glycoprotein was overexpressed in resistant cells. The intracellular ADR level of resistant cells was lower than that of parent cells. One micro g/ml CEP eliminated the degradation of intracellular ADR of resistant cells; that is, to a level equivalent to that of the parent cells. CEP of 0.5 micro g/ml, which was not cytotoxic when used alone, significantly increased the ADR sensitivity of resistant cells, to a level similar to the parent cell level. Isosorbide 5-mononitrate, a potential nitric oxide-generation agent, combined with CEP further increased the ADR sensitivity of resistant cells, indicating a synergistic effect of CEP and isosorbide 5-mononitrate on ADR cytotoxicity. Time-lapse microscopic observation revealed that ADR dominantly induced apoptosis much more than necrosis for both parent and resistant cells, and that the use of 0.5 micro g/ml CEP with ADR synergistically accelerated apoptosis in resistant cells. Finally, we clarified the property by which CEP synergistically accelerates ADR-induced apoptosis. This property might be a new mechanism that explains how CEP overcomes ADR resistance.
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PMID:Cepharanthin enhances adriamycin sensitivity by synergistically accelerating apoptosis for adriamycin-resistant osteosarcoma cell lines, SaOS2-AR and SaOS2 F-AR. 1520 88

Osteosarcoma (OS) is the most common primary malignant bone tumor and mainly affects children and adolescents. The OS five-year survival rate remains very low. Thus, novel therapeutic protocols for the treatment of OS are needed. Several approaches targeting deregulated signaling pathways have been proposed. The antitumoral effects of polyphenols, which are naturally occurring compounds with potent antioxidant and anti-inflammatory activity, have been investigated in different tumors. Gossypol, which is a natural polyphenolic aldehyde isolated from the seeds of the cotton plant, has been shown to exert antitumoral activity in leukemia and lymphoma and in breast, head and neck, colon and prostate cancers. Therefore, in this study, we evaluated the effect of AT-101, which is the (-) enantiomer and more active form of gossypol, on the growth of human and murine OS cells in vitro and in vivo. Several clinical trials employing AT-101 have been performed, and some clinical trials are ongoing. Our results showed for the first time that AT-101 significantly inhibits OS cell growth in a dose- and time-dependent manner, inducing apoptosis and necrosis and partially activating autophagy. Our results demonstrated that AT-101 inhibits prosurvival signaling pathways depending on Akt, p38 MAPK and JNK. In addition, treatment with AT-101 increases the survival of OS-bearing mice. Overall, these results suggest that AT-101 is a candidate chemo-supportive molecule for the development of novel chemotherapeutic protocols for the treatment of OS.
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PMID:In vivo and in vitro inhibition of osteosarcoma growth by the pan Bcl-2 inhibitor AT-101. 3126 66