[Effects of triptolide on the apoptosis and H3K4 protein methylation in multiple myeloma cells].

Objective: To investigate the effects of triptolide (Chinese Traditional Medicine)on the apoptosis and H3K4 protein methylation in multiple myeloma cells.

Methods: The RPMI8226 cells were cultured with different concentrations(10,20,40,80 and 160 nmol/L)of triptolide for different incubation time (24 h,48 h and 72 h). The inhibition of triptolide on RPMI8226 cell proliferation was detected by MTT assay. Apoptosis and cell cycle distribution were evaluated by flow cytometry.The expressions of H3K4me2 and trimethylation of histone H3 lysine 4(H3K4me3) in RPMI8226 cells were assayed by Western blot. The changes of expressions of histone methylase SET and MYND domain containing 3(SMYD3) and histone demethylase lysine specific demethylase 1(LSD1) in RPMI8226 cells were verified by qRT-PCR.

Results: Triptolide had obvious inhibitive effects on proliferation of RPMI8226 cells and showed a dose-and time-dependent manner(<0.05). Triptolide induced apoptosis and G/M cell cycle arrest in a dose-dependent manner(<0.05). Triptolide decreased histone H3K4me2 and H3K4me3 expression in a dose-dependent manner(<0.05, <0.01). SMYD3 was significantly depressed at protein expression in a dose-dependent manner(<0.05), but LSD1 was up-regulated (<0.05).

Conclusions: Triptolide could inhibit RPMI8226 cell proliferation,induce the apoptosis and cause G/M arrest,meanwhile,significantly inhibit the protein expressions of H3K4me2 and H3K4me2 with alter the expression of SMYD3 and LSD1.The effects is probably related to the antitumor mechanism of MM cells induced by triptolide.