Balanitin-6 and -7: Diosgenyl saponins isolated from Balanites aegyptiaca Del. display significant anti-tumor activity in vitro and in vivo
| Autor: | Nancy De Nève, Jacques Dubois, Robert Kiss, Florence Lefranc, Véronique Megalizzi, Pierre Duez, Charlemagne Gnoula, Laurent Ingrassia, Sébastien Sauvage, Tatjana Mijatovic, Pierre Guissou, Fabrice Ribaucour |
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| Rok vydání: | 2008 |
| Předmět: |
Cancer Research
Cell Apoptosis Diosgenin Pharmacology Biology Mice Adenosine Triphosphate In vivo Cell Line Tumor medicine Animals Humans Balanites Leukemia L1210 Etoposide Cell Cycle Biological activity Saponins Cell cycle Actin cytoskeleton Antineoplastic Agents Phytogenic In vitro Mice Inbred C57BL medicine.anatomical_structure Oncology Biochemistry Mice Inbred DBA Female Reactive Oxygen Species medicine.drug |
| Zdroj: | International Journal of Oncology. |
| ISSN: | 1791-2423 1019-6439 |
| Popis: | Balanites aegyptiaca is a widely distributed African plant of medicinal interest containing a number of cytotoxic and cytostatic compounds. The studies reported here have attempted to further characterize the anti-cancer activity of a mixture of steroidal saponins: balanitin-6 (28%) and balanitin-7 (72%) isolated from Balanites aegyptiaca kernels. The balanitin-6 and -7 mixture (henceforth referred to as bal6/7) has demonstrated appreciable anti-cancer effects in human cancer cell lines in vitro. Bal6/7 displayed higher anti-proliferative activity than etoposide and oxaliplatin, although the mixture was appreciably less active than SN38 and markedly less active than taxol. Bal6/7 demonstrated highest activity against A549 non-small cell lung cancer (NSCLC) (IC(50), 0.3 microM) and U373 glioblastoma (IC(50), 0.5 microM) cell lines. The current study has further indicated that bal6/7 is more a cytotoxic compound than a cytostatic one. However, Bal6/7 does not appear to mediate its anti-proliferative effects by inducing apoptotic cell death. Computer-assisted cellular imaging has revealed that bal6/7 does not induce detergent-like effects in A549 NSCLC and U373 glioblastoma unlike certain saponins. Furthermore there is indication that its in vitro anti-cancer activities result at least partly from depletion of [ATP]i, leading in turn to major disorganization of actin cytoskeleton, ultimately resulting in the impairment of cancer cell proliferation and migration. In contrast to a number of natural products acting as anti-cancer agents, bal6/7 does not induce an increase in intra-cellular reactive oxygen species. In vivo, bal6/7 increased the survival time of mice bearing murine L1210 leukemia grafts to the same extent reported for vincristine. These preliminary in vivo data suggest that it may be possible to generate novel hemi-synthetic derivatives of balanitin-6 and -7 with potentially improved in vitro and in vivo anti-cancer activity and reduced in vivo toxicity, thus markedly improving the therapeutic ratio. |
| Databáze: | OpenAIRE |
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