Curcumin Analogue, Hydrazinocurcumin, Exhibits Potent Suppressive Activity On Carcinogenicity Of Breast Cancer Cells Via STAT3 Inhibition

Objective To investigate the effect of curcumin derivant (hydrazinocurcumin, HC) on human breast cancer of MDA-MB-231, MCF-7 cells, and elucidate its mechanisms whether it inhibited the STAT3 signal pathway.Methods The human breast cancer cells MDA-MB-231, MCF-7 were divided into 3 groups, control group, curcumin treatment group and HC treatment group. IC50 values for curcumin and HC were calculated with MTT assay. The ability of the cells colony formation was detected by the soft agar colony formation assay. FCM was performed to determine the cell cycle and cells apoptosis. The migration of MDA-MB-231 and MCF-7 cells was measured with scratch assay, and invasion was measured by Transwell chamber. Expression of STAT3 and its downstream targets, such as Cyclin D1, C-myc, Mcl-1, Survivin, Bcl-2, Bcl-xl, MMP2, MMP9, VEGF, were detected by Western blot analysis.Results MTT assay showed the IC₅0 of HC was 3.37μmol/L compared with 26.9μmol/L of curcumin in MDA-MB-231 cell, and 2.56μmol/L compared with 21.22μmol/L in MCF-7 cell. Compared with the DMSO control samples, a 5μmol/L concentration of curcumin produced a decrease of nearly 50% in colony formation, while equal concentration of HC showed approximately 95% reduction in colony number. HC and curcumin treatment at a concentration of 10μmol/L had an obviously effect on elevation of the cell number in the G1 phase in MDA-MB-231, MCF-7 (P<0.05 compared with control), and moreover, HC was more potent than curcumin in arrest the cells cycle in G1 phase. Compared with the DMSO control samples, both drugs had the ability to induce apoptosis in two breast cancer cells, and HC was more potent than curcumin. The scratch and invasion assay also showed that HC had more capability to decrease the cell migration and invasion compared with curcumin (P<0.05).The Western blot analysis demonstrated that the expressions of p-STAT3 and its downstream targets, such as Cyclin D1, C-myc, Mcl-1, Survivin, Bcl-2, Bcl-xl, MMP2, MMP9, VEGF, were decreased by HC and curcumin, and HC was more potent than curcumin.Conclusion Compared with curcumin, HC was more effective in inhibition STAT3 phosphorlation and downregulation an array of STAT3 downstream targets which contributed to suppression of cell proliferation, loss of colony formation, depression of cell migration and invasion as well as induction cell apoptosis. HC was more favorable pharmacological activity than curcumin, and might have translational potential as effective cancer therapeutics or preventive agent for human breast carcinoma.