09 February 2020 : Laboratory Research
The Effects of (11R)-13-(6-Nitroindazole)-11,13-Dihydroludartin on Human Prostate Carcinoma Cells and Mouse Tumor Xenografts
Longning Wang1BCD, Lei Wang1BCD, Sen Wei1BC, Xiaodong Wang1CD, Daqing Shen23ACDEF*DOI: 10.12659/MSM.920389
Med Sci Monit 2020; 26:e920389
Abstract
BACKGROUND: This study aimed to investigate the effects of the 6-nitroindazole compound and amino analog of ludartin, (11R)-13-(6-nitroindazole)-11,13-dihydroludartin (NDHL), on human prostate carcinoma cells in vitro and in mouse tumor xenografts in vivo.
MATERIAL AND METHODS: DU-145 and LNCaP human prostate carcinoma cells were cultured with increasing concentrations of NDHL. Cell viability was measured using the MTT assay, and cell apoptosis was measured by fluorescence flow cytometry. Mouse tumor xenografts were created by implanting 2×10⁶ of DU-145 cells subcutaneously in the left flank. On the second day following DU-145 cell implantation, the mice in the treatment groups were injected intraperitoneally with 2, 5, and 10 mg/kg of NDHL.
RESULTS: Treatment of DU-145 and LNCaP cells with NDHL (range, 2.5–20.0 μM) significantly reduced cell proliferation in vitro (P<0.05). The proliferation rate of DU-145 and LNCaP cells was reduced to 27% and 24%, respectively, following treatment with 20.0 μM of NDHL. Treatment with NDHL significantly increased cell apoptosis and the formation of reactive oxygen species (ROS) formation in DU-145 cells at 48 h (P<0.05). NDHL significantly increased the proportion of DU-145 cells in the G1 phase of the cell cycle and significantly increased the expression of cyclin D1 and p21 (P<0.05). Treatment of the mice in the xenograft tumor model with NDHL significantly increased survival and suppressed tumor growth (P<0.02).
CONCLUSIONS: NDHL inhibited cell proliferation, increased apoptosis, and caused cell cycle arrest in human prostate carcinoma cells in vitro and inhibited mouse tumor xenograft growth in vivo.
Keywords: Cell Cycle Checkpoints, Cyclin-Dependent Kinase Inhibitor p21, Indazoles, Prostatic Neoplasms, Santonin
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