Thymoquinone Augments Cyclophosphamide-MediatedInhibition of Cell Proliferation in Breast Cancer Cells
Anahtar kelimeler
Öz
Objective: Cancer chemotherapy at the recommended doses is largely associated with toxicity, and also it is noteffective enough to reduce the advancement of the disease at lower doses. Thymoquinone (TQ) is an active compoundderived from black seeds (Nigella sativa) which exhibits anticancer activities. The aim of the present study was toinvestigate the synergistic effect of TQ alone and in combination with cyclophosphamide (cyclo), and to unravel therole of TQ in fatty acid synthase (FASN) mediated molecular signaling in Her2 + and Her2- breast cancer cell lines.Methods: The effect of TQ on the growth of Her2+ SKBR-3 and Her2- MDA-231 breast cancer lines were evaluatedas percent cell viability by cytotoxicity-based MTT assay. The analysis of cell cycle arrest was done through flowcytometryfollowed by Western blot and RT-PCR to detect signaling events in the cells. Results: The data showedthat TQ-cyclo (0.5mM-10μM) combination significantly inhibited the proliferation through the 5.49% and 57.72%accumulation of cells in sub-G1 and G1 respectively as 12% cells were shifted from G2/M phase in Her2+ breast cancercells. Similarly, TQ-cyclo (0.5mM-20μM) combination exhibited that the 16.6% cells were arrested in Sub-G1 and only3.54% cells were remained in G2/M phase as it was 22.89% in DMSO control in Her-2- breast cancers cells. ThoughTQ alone or in combination with cyclo alleviated the PI3K/Akt signaling by downregulating the phosphorylation of Aktand upregulating the PTEN, no changes was observed in FASN and Her-2 as well in both type of cells. The significantdecreased expression of cyclin D1 was found in TQ-cyclo combinations. Conclusion: The current findings suggestedthat TQ can alter the cell cycle progression and induce cell death independent of FASN mediated signaling. In terms ofclinical perspective, the present study clearly showed that TQ can broadly augment the effect of cyclo in breast cancercases irrespective of Her-2+ or Her-.
