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Reactive oxygen species-mediated apoptosis contributes to chemosensitization effect of saikosaponins on cisplatin-induced cytotoxicity in cancer cells
- Source :
- Journal of Experimental & Clinical Cancer Research : CR, Journal of Experimental & Clinical Cancer Research, Vol 29, Iss 1, p 159 (2010)
- Publisher :
- Springer Nature
-
Abstract
- Background Saikosaponin-a and -d, two naturally occurring compounds derived from Bupleurum radix, have been shown to exert anti-cancer activity in several cancer cell lines. However, the effect of combination of saikosaponins with chemotherapeutic drugs has never been addressed. Thus, we investigated whether these two saikosaponins have chemosensitization effect on cisplatin-induced cancer cell cytotoxicity. Methods Two cervical cancer cell lines, HeLa and Siha, an ovarian cancer cell line, SKOV3, and a non-small cell lung cancer cell line, A549, were treated with saikosaponins or cisplatin individually or in combination. Cell death was quantitatively detected by the release of lactate dehydrogenase (LDH) using a cytotoxicity detection kit. Cellular ROS was analyzed by flow cytometry. Apoptosis was evaluated by AO/EB staining, flow cytometry after Anexin V and PI staining, and Western blot for caspase activation. ROS scavengers and caspase inhibitor were used to determine the roles of ROS and apoptosis in the effects of saikosaponins on cisplatin-induced cell death. Results Both saikosaponin-a and -d sensitized cancer cells to cisplatin-induced cell death in a dose-dependent manner, which was accompanied with induction of reactive oxygen species (ROS) accumulation. The dead cells showed typical apoptotic morphologies. Both early apoptotic and late apoptotic cells detected by flow cytometry were increased in saikosaponins and cisplatin cotreated cells, accompanied by activation of the caspase pathway. The pan-caspase inhibitor z-VAD and ROS scanvengers butylated hydroxyanisole (BHA) and N-acetyl-L-cysteine (NAC) dramatically suppressed the potentiated cytotoxicity achieved by combination of saikosaponin-a or -d and cisplatin. Conclusions These results suggest that saikosaponins sensitize cancer cells to cisplatin through ROS-mediated apoptosis, and the combination of saikosaponins with cisplatin could be an effective therapeutic strategy.
- Subjects :
- Cancer Research
Blotting, Western
Apoptosis
Cell Separation
Biology
lcsh:RC254-282
Flow cytometry
Chemosensitization
Cell Line, Tumor
Neoplasms
Antineoplastic Combined Chemotherapy Protocols
medicine
Humans
Oleanolic Acid
Cytotoxicity
chemistry.chemical_classification
Cisplatin
Reactive oxygen species
medicine.diagnostic_test
Research
Saponins
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Flow Cytometry
Molecular biology
Oncology
chemistry
Cell culture
Cancer cell
Cancer research
Reactive Oxygen Species
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 17569966
- Volume :
- 29
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental & Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....83fc90934948b196643fe78ab505a0fd
- Full Text :
- https://doi.org/10.1186/1756-9966-29-159