| Objective: In effort to screen compounds of significant anti-tumor activity from Tetrandrine derivatives, Inhibition of the screened compounds on proliferation of MDA-MB-435 cells, GRC-1 cells and Tca8113 cells was explored and the expression of BLM helicase was also detected on MDA-MB-435 cells effected by the compounds. Methods: Tetrandrine derivatives which could have inhibiton on MDA-MB-435 was investigated by MTT assay. The inhibition of the screened compounds on MDA-MB-435 cells were detected by colony formation assay.Hochest33342 staining and flow cytometry were applied to analyse the apoptosis of MDA-MB-435 cells. The expression of BLM helicase, apoptosis protein Caspase-3, Bax and Bcl-2 was tested by western blotting. And the cytotoxic activity against BCSCs was detected by MTT assay. Results: HL-42 and HL-49 with singnificantly proliferative inhibition on MDA-MB-435 cells were screened from Tetrandrine derivatives, and the IC50(48h) was 2.5 μM, 2.2 μM, respectively. Also,they have obvrious inhibited effect on breast cancer stem cells, and the IC50(48h) was1.9 μM and 1.7 μM, respectively. The growth inhibition effect with time extension of HL-42 and HL-49 was detected. Then, the apoptosis of MDA-MB-435 treated with HL-42 and HL-49 was detected. On the concentration of 2 μM and 10 μM, the apoptoic rate of HL-42 to MDA-MB-435 cells was 40.2% and 91.77%, respectively.Simulatiously, the apoptoic rate of HL-49 to MDA-MB-435 was, respectively,49.89% and 96.14% on the same concentration. Moreover, the western blotting results indicated that BLM helicase, apoptosis protein Caspase-3 and Bax was upregulated in MDA-MB-435 cells by HL-42 and HL-49, moreover, the expression of Bcl-2 was down-regulated. Conclusion: Tetrandrine derivatives—HL-42 and HL-49 have significant inhibition on MDA-MB-435 cells and BCSCs. The expression of Caspse-3,Bax and Bcl-2 indicated that HL-42 and HL-49 can induce the apoptosis of MDA-MB-435 cells, which may be associated with DNA damage. |
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