Objective: To investigate the anticancer effect and mechanism of parthenolide analogue (PTLA-1) on adriamycin resistant human chronic myeloid leukemia cell line K562/ADR cells. Methods K562/ADR cells were cultured in vitro. The inhibitory effects of PTLA-1 on cell proliferation were detected by MTT assay, and the effects of PTLA-1 on K562/ADR cell cycle, apoptosis, mitochondrial membrane potential (ΔΨm) and reactive oxygen species were detected by flow cytometry. The effects of PTLA-1 on K562/ADR cell cycle and apoptosis related proteins expressions were detected by Western blot. Results PTLA-1 had higher inhibitory activity on K562/ADR cells than parthenolide. It inhibited the expressions of Cyclin B1/D1 and CDK1/2/4/6, resulting in the arrest of K562/ADR cells in G0/G1 phase; PTLA-1 induced apoptosis of K562/ADR cells in mitochondrial pathway. PTLA-1 could induce mitochondrial membrane potential (ΔΨm) and down regulate the expressions of reactive oxygen species, Bcl-2 and p-Akt proteins, and up regulate the expressions of Bax, cyto c, caspase 9/3 proteins. The chromatin of K562/ADR cells contracted and apoptotic bodies appeared. Conclusion Parthenolide analogue PTLA-1 could inhibit cell proliferation by causing K562/ADR cells to block in G0/G1 phase. Secondly, it could induce K562/ADR cells to apoptosis through caspase dependent mitochondrial pathway, which was related to Akt signal pathway. It had certain anticancer therapeutic potential for chronic myeloid leukemia.

Jie Ren, Yi Xing, Yuexin Zhao, Kun Hu. Anticancer Mechanism of Parthenolide Analogue PTLA-1 on Adriamycin Resistant Human Chronic Myeloid Leukemia Cell Line K562/ADR. Frontiers in Medical Science Research (2022) Vol. 4, Issue 5: 27-35. https://doi.org/10.25236/FMSR.2022.040506.

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