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Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells.


ABSTRACT: The aim of the present study was to investigate the specific effect and possible mechanisms of phenylhexyl isothiocyanate (PHI) on cell proliferation and apoptosis in acute myeloid leukemia M2 cell lines. Cell proliferation in several hematological tumor cells lines following PHI treatment was evaluated in vitro using a Cell Counting Kit-8. The apoptosis and cell cycle of Kasumi-1 and SKNO-1 cells (human M2 cell lines) following exposure to PHI were examined using flow cytometry. A colony-formation assay was used to identify the inhibitory effect of PHI on Kasumi-1 cells in vitro. Furthermore, Kasumi-1 ×enograft tumor models were established. The antitumor effect of PHI was observed in vivo by measuring the size of the resulting xenograft tumors. The apoptosis of the xenograft tumor cells was measured using a TUNEL assay. Finally, protein expression levels were assessed by western blotting. PHI inhibited cell growth in 16 hematological tumor cell lines, with Kasumi-1 and SKNO-1 cells being the most sensitive. In vitro treatment induced apoptosis and inhibited cell cycle arrest at the G0/G1 phase in a dose- and time-dependent manner. PHI also inhibited growth and induced apoptosis in vivo. The compound increased the expression of caspases 3, 9 and 8, Fas and poly (ADP-ribose) polymerase. Furthermore, PHI enhanced the protein expression of p53, Bax and p21 in a dose-dependent manner. In conclusion, PHI had a specific and notable inhibitory effect on Kasumi-1 and SKNO-1 M2 cell lines in vivo and in vitro. Treatment inhibited cell cycle arrest at the G0/G1 phase, and induced apoptosis through the mitochondrial and Fas death receptor pathways. PHI restored the activity of mutated P53 and reactivated the P53 pathway, highlighting it as a potential target drug for mutated P53.

SUBMITTER: Zou Y 

PROVIDER: S-EPMC6676407 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant <i>P53</i> in human myeloid leukemia M2 cells.

Zou Yong Y   Huang Yiqun Y   Ma Xudong X  

Oncology letters 20190716 3


The aim of the present study was to investigate the specific effect and possible mechanisms of phenylhexyl isothiocyanate (PHI) on cell proliferation and apoptosis in acute myeloid leukemia M2 cell lines. Cell proliferation in several hematological tumor cells lines following PHI treatment was evaluated <i>in vitro</i> using a Cell Counting Kit-8. The apoptosis and cell cycle of Kasumi-1 and SKNO-1 cells (human M2 cell lines) following exposure to PHI were examined using flow cytometry. A colony  ...[more]

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