STAT3-mediated Apoptotic-enhancing Function of SclareolAgainst Breast Cancer Cells and Cell Sensitization toCyclophosphamide

Sclareol is an organic compound with potential anti-tumor effects against various cancer types.however, its precise molecular mechanism in the suppression of tumor growth has not been fullyelucidated. in the present study, the anti-proliferative and apoptosis-inducing effects of sclareolwith cyclophosphamide were investigated in breast cancer cells and the involvement of the jak/stat pathway was evaluated. for this purpose, mcf-7 breast cancer cells were cultured andtreated with various concentrations of sclareol to determine its ic50. cell viability was measuredby mtt assay and apoptosis was assessed by flow cytometric analysis of annexin v binding.gene and protein expression were examined by real-time pcr and western blotting, respectively.the activity of caspase enzymes was also measured. the results showed that sclareol significantlyreduced cell viability and triggered cell death and its co-administration with cyclophosphamideenhanced its anti-cancer properties. additionally, sclareol up-regulated the expression ofp53 and bax and reduced the expression of bcl-2. docking studies indicated an interactionbetween sclareol and stat3 which was proved by attenuation of stat3 phosphorylation aftertreatment of the cells with sclareol. sclareol was also capable of suppressing the function ofil-6 in modulating the expression of apoptosis-associated genes. altogether these data suggestthe potential of sclareol as an anti-cancer agent and demonstrate that a combination of sclareolwith cyclophosphamide might serve as an effective chemotherapeutic approach resulting inimprovements in the treatment of breast cancer.