| In vitro: |
| Chemical & Pharmaceutical Bulletin, 1994, 42(3):611-616. | | Studies on Differentiation Inducers. IV. Pregnane Derivatives from Condurango Cortex.[Reference: WebLink] |
METHODS AND RESULTS:
In connection with the study of differentiation inducers from plants, the methanol extract of Condurango Cortex (bark of Marsdenia condurango REICH, Asclepiadaceae) was investigated to examine its differentiation-inducing activity towards mouse myeloid leukemia (M1) cell line. Six pregnane glycosides, including three new compounds, were isolated as differentiation inducers. Each of the six active glycosides has three or four deoxylated sugars which are well-known to occur in Asclepiadaceae plants. M1 cells were differentiated into phagocytic cells by these glycosides, and they were found to be more effective than their aglycones.
CONCLUSIONS:
Condurango glycoside A (7) and Condurango glycoside C (8), having a cinnamoyl group in their aglycones, were the most potent differentiation inducers and M1 cells became phagocytic cells after 24 h treatment with these compounds. | | Molecular and Cellular Biochemistry, 2013, 382(1-2):173-183. | | Condurango-glycoside-A fraction of Gonolobus condurango induces DNA damage associated senescence and apoptosis via ROS-dependent p53 signalling pathway in HeLa cells.[Reference: WebLink] | Gonolobus condurango plant extract is used as an anticancer drug in some traditional systems of medicine including homeopathy, but it apparently lacks any scientific validation. Further, no detailed study is available to suggest whether Condurango glycoside A (CGA), a major ingredient of condurango serves as a potent anticancer compound. Therefore, we investigated apoptosis-inducing ability of CGA against cervix carcinoma cells (HeLa).
METHODS AND RESULTS:
β-galactosidase-activity and DNA damage were critically studied at different time points; while induced DNA-damage was observed at 9–12th hours, senescence of cells appeared at a later stage (18th hour after CGA treatment), implicating thereby a possible role of DNA damage in inducing pre-mature cell senescence. Concurrently, the number of cells undergoing apoptosis increased along with increase in reactive oxygen species (ROS) generation. Expression of p53 was also up-regulated, indicating that apoptosis could have been mediated through p53 pathway. DCHFDA (4′,6-Diamidino-2-phenylindole dihydrochloride) assay, acridine orange/ethidium bromide staining and annexin V/PI assay results collectively confirmed that apoptosis was induced by increased ROS generation. Reduction in proliferation of cells was further evidenced by the cell cycle arrest at G0/G1 stage. Expression profiles of certain relevant genes and proteins like p53, Akt, Bcl-2, Bax, cytochrome c and caspase 3 also provided evidence of ROS mediated p53 up-regulation and further boost in Bax expression and followed by cytochrome c release and activation of caspase 3.
CONCLUSIONS:
Overall results suggest that CGA initiates ROS generation, promoting up-regulation of p53 expression, thus resulting in apoptosis and pre-mature senescence associated with DNA damage. |
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