Resistance to apoptosis of harringtonine-resistant HL60 cells induced by tetrandrine.

ABSTRACT

AIM: To study the mechanism of resistance to apoptosis in the harringtonine (Har)-resistant HL60 cells with tetrandrine (Tet). METHODS: Growth inhibition, flow cytometry, DNA agarose gel electrophoresis, protein phosphorylation, and RNA dot hybridization. RESULTS: The resistant cells had no cross resistance to Tet. Tet induced the sensitive but not the Har-resistant HL60 cells to apoptosis. The high phosphorylation of protein < 30 kDa occurred when the resistant cells were treated with Tet. Tet and Har increased the expression of c-myc mRNA in the sensitive HL60 cells. The expression of c-myc mRNA in the resistant cells was obviously decreased and almost not changed in treatment with Tet and Har. CONCLUSION: Tet induced the sensitive but not the Har-resistant HL60 cells to apoptosis, and the resistance to apoptosis induced by Tet was associated with the high protein phosphorylation and reduction of the expression of c-myc mRNA.