The p53 Modulated Cytotoxicity of Polysaccharide Against Resistance Ovarian Cancer Cells.

BACKGROUND

Marine environment is a valuable source of bioactive compounds with variable medicinal properties. Previously, it was shown that extracted polysaccharide has prominent cytotoxic effect on HeLa human cervical cancer cells. In the present study, the anti-cancer properties of polysaccharide extracted from ( were examined in comparison with paclitaxel as a conventional drug against resistant ovarian cancer; also, its related mechanism against A2780cp ovarian cancer cells was investigated.

METHODS

The A2780cp cancer cells and NIH3T3 normal cells were cultured and treated with different concentrations of polysaccharide extracted from for 24 and 48 . Then, cell toxicity was studied by MTT assay, morphology of cells was observed under inverted microscopy and the type of induced cancer cell death was assessed by annexin V-FITC, propodium iodide and acridine orange staining. Finally, the apoptosis pathway was determined by measurement of caspase-3 and caspase-9 activity and assessment of p53 and Bcl-2. The statistical analysis was performed by SPSS software, one way ANOVA and p<0.05 was considered significant.

RESULTS

Our observations from MTT assay and morphological assessment exhibited that isolated polysaccharide inhibited proliferation of ovarian cancer cells with IC of 35 , while paclitaxel suppressed tumor cell growth with IC=10 . In contrast, MTT observations revealed low cytotoxicity of these chemotherapeutic agents against NIH3T3 normal cells. Also, the analysis correlated with induced cell death elucidated that concurrent treatment of polysaccharide plus paclitaxel had a further anti-cancer effect against A2780cp cells mainly through restoration of p53 and mitochondrial apoptosis cell death induction.

CONCLUSION

Taken together, our research supports the finding that application of polysaccharide extracted from can be considered a promising marine chemotherapeutic approach for advancing efficacy of paclitaxel in treatment of resistant ovarian cancer. Additional experiments are required to elucidate the role of brittle star polysaccharides in animal and clinical trials.