- Title
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Natural Product Micheliolide (MCL) Irreversibly Activates Pyruvate Kinase M2 and Suppresses Leukemia
- Authors
- Li, J., Li, S., Guo, J., Li, Q., Long, J., Ma, C., Ding, Y., Yan, C., Li, L., Wu, Z., Zhu, H., Li, K.K., Wen, L., Zhang, Q., Xue, Q., Zhao, C., Liu, N., Ivanov, I., Luo, M., Xi, R., Long, H., Wang, P.G., Chen, Y.
- Source
- Full text @ J. Med. Chem.
Anticancer effects of DMAMCL are dependent on PKM2. (A) Western blot detection of the expression of PKM1, PKM2, and PKM in the absence of endogenous PKM2, which was knocked down with short hairpin RNA. (B) Cell-based detection of pyruvate activity of HL60 cells with shPKM2 and shControl. (C) Cell viability detection of pyruvate activity of HL60 cells with shPKM2 and shControl. (D) PKM2 depletion desensitizes cancer cells to MCL treatment. (E) Representative fluorescent images of HL60 cell xenografted zebrafishes with treatment of DMAMCL, cytarabine, or negative control. Approximately 300 HL60 cells were injected into the yolk sac of embryos. After injections, xenografted embryos were treated with a series of doses of DMAMCL (1, 3, 10 μg/mL), cytarabine at 200 μg/mL as a positive drug control, and saline as a negative control. After 3 days of incubation, the number of embryos exhibiting cancer cell dissemination was counted by microscopic observation (15 larvae/group). Data represent the average ± SD of three independent assays. *P < 0.05. **P < 0.01. |