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Article

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

  • Authors:
    • Yong Zou
    • Yiqun Huang
    • Xudong Ma
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, Zhangzhou Affiliated Hospital of Fujian Medical University, Zhangzhou, Fujian 363000, P.R. China
  • Pages: 3358-3366
    |
    Published online on: July 16, 2019
       https://doi.org/10.3892/ol.2019.10620
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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 xenograft 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.
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1 

Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR and Sultan C: Proposals for the classification of the acute leukaemias French-American-British (FAB) Co-operative Group. Br J Haematol. 33:451–458. 1976. View Article : Google Scholar : PubMed/NCBI

2 

Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, et al: Diagnosis and management of acute myeloid leukemia in adults: Recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 115:453–474. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Dohner H, Weisdorf DJ and Bloomfield CD: Acute Myeloid Leukemia. N Engl J Med. 373:1136–1152. 2015. View Article : Google Scholar : PubMed/NCBI

4 

Ferrara F and Del Vecchio L: Acute myeloid leukemia with t(8;21)/AML1/ETO: A distinct biological and clinical entity. Haematologica. 87:306–319. 2002.PubMed/NCBI

5 

Isobe M, Emanuel BS, Givol D, Oren M and Croce CM: Localization of gene for human p53 tumour antigen to band 17p13. Nature. 320:84–85. 1986. View Article : Google Scholar : PubMed/NCBI

6 

Levine AJ: p53, the cellular gatekeeper for growth and division. Cell. 88:323–331. 1997. View Article : Google Scholar : PubMed/NCBI

7 

Gualberto A, Aldape K, Kozakiewicz K and Tlsty TD: An oncogenic form of p53 confers a dominant, gain-of-function phenotype that disrupts spindle checkpoint control. Proc Natl Acad Sci USA. 95:5166–5171. 1998. View Article : Google Scholar : PubMed/NCBI

8 

Carson DA and Lois A: Cancer progression and p53. Lancet. 346:1009–1011. 1995. View Article : Google Scholar : PubMed/NCBI

9 

Amundson SA, Myers TG and Fornace AJ Jr: Roles for p53 in growth arrest and apoptosis: Putting on the brakes after genotoxic stress. Oncogene. 17:3287–3299. 1998. View Article : Google Scholar : PubMed/NCBI

10 

Kirsch DG and Kastan MB: Tumor-suppressor p53: Implications for tumor development and prognosis. J Clin Oncol. 16:3158–3168. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Toshinori O and Akira N: Role of p53 in cell death and human cancers. Cancers. 3:994–1013. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Petitjean A, Mathe E, Kato S, Ishioka C, Tavtigian SV, Hainaut P and Olivier M: Impact of mutant p53 functional properties on TP53 mutation patterns and tumor phenotype: Lessons from recent developments in the IARC TP53 database. Hum Mutat. 28:622–629. 2007. View Article : Google Scholar : PubMed/NCBI

13 

Orazi A, Cattoretti G, Heerema NA, Sozzi G, John K and Neiman RS: Frequent p53 overexpression in therapy related myelodysplastic syndromes and acute myeloid leukemias: An immunohistochemical study of bone marrow biopsies. Mod Pathol. 6:5211993.PubMed/NCBI

14 

Cleven AH, Nardi V, Ok CY, Goswami M, Dal Cin P, Zheng Z, Iafrate AJ, Abdul Hamid MA, Wang SA and Hasserjian RP: High p53 protein expression in therapy-related myeloid neoplasms is associated with adverse karyotype and poor outcome. Mod Pathol. 28:552–563. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Lane DP, Cheok CF and Lain S: p53-based cancer therapy. Cold Spring Harb Perspect Biol. 2:a0012222010. View Article : Google Scholar : PubMed/NCBI

16 

Di Agostino S, Cortese G, Monti O, Dell'Orso S, Sacchi A, Eisenstein M, Citro G, Strano S and Blandino G: The disruption of the protein complex mutantp53/p73 increases selectively the response of tumor cells to anticancer drugs. Cell Cycle. 7:3440–3447. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Zhang S, Zhou L, Hong B, van den Heuvel AP, Prabhu VV, Warfel NA, Kline CL, Dicker DT, Kopelovich L and El-Deiry WS: Small-Molecule NSC59984 restores p53 pathway signaling and antitumor effects against colorectal cancer via p73 activation and degradation of mutant p53. Cancer Res. 75:3842–3852. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Chiao JW, Wu H, Ramaswamy G, Conaway CC, Chung FL, Wang L and Liu D: Ingestion of an isothiocyanate metabolite from cruciferous vegetables inhibits growth of human prostate cancer cell xenografts by apoptosis and cell cycle arrest. Carcinogenesis. 25:1403–1408. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Lu L, Liu D, Ma X, Beklemishev A, Seiter K, Ahmed T and Chiao JW: The phenylhexyl isothiocyanate induces apoptosis and inhibits leukemia cell growth in vivo. Oncol Rep. 16:1363–1367. 2006.PubMed/NCBI

20 

Ma X, Fang Y, Beklemisheva A, Dai W, Feng J, Ahmed T, Liu D and Chiao JW: Phenylhexyl isothiocyanate inhibits histone deacetylases and remodels chromatins to induce growth arrest in human leukemia cells. Int J Oncol. 28:1287–1293. 2006.PubMed/NCBI

21 

Zhuang Z, Huang Y, Ma X, et al: Histone Methylation and Acetylation Modulated by PHI in Prostate Cancer PC3 Cell Line Acta Medicinae Universitatis Scientiae Et Technologiae Huazhong 06. 2012.

22 

Lai YD, Ma XD, Huang YQ, Xu XN, Wang XZ, Chiao DJ and Liu D: Modulation of histone acetylation and induction of apoptosis in SMMC-7721 cells by phenylhexyl isothiocyanate. Zhonghua Zhong Liu Za Zhi. 32:8042010.(In Chinese). PubMed/NCBI

23 

Jiang S, Ma X, Huang Y, Xu Y, Zheng R and Chiao JW: Reactivating aberrantly hypermethylated p15 gene in leukemic T cells by a phenylhexyl isothiocyanate mediated inter-active mechanism on DNA and chromatin. J Hematol Oncol. 3:482010. View Article : Google Scholar : PubMed/NCBI

24 

Yong Z, Ma X, Huang Y, Hong L and Chiao J: Effect of phenylhexyl isothiocyanate on aberrant histone H3 methylation in primary human acute leukemia. J Hematol Oncol. 5:362012. View Article : Google Scholar : PubMed/NCBI

25 

Del PG, Venditti A, Del Principe MI, Maurillo L, Buccisano F, Tamburini A, Cox MC, Franchi A, Bruno A, Mazzone C, et al: Amount of spontaneous apoptosis detected by Bax/Bcl-2 ratio predicts outcome in acute myeloid leukemia (AML). Blood. 101:2125–2131. 2003. View Article : Google Scholar : PubMed/NCBI

26 

Redza-Dutordoir M and Averill-Bates DA: Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta. 1863:2977–2992. 2016. View Article : Google Scholar : PubMed/NCBI

27 

Kischkel FC, Lawrence DA, Tinel A, LeBlanc H, Virmani A, Schow P, Gazdar A, Blenis J, Arnott D and Ashkenazi A: Death receptor recruitment of endogenous caspase-10 and apoptosis initiation in the absence of caspase-8. J Biol Chem. 276:466392001. View Article : Google Scholar : PubMed/NCBI

28 

Boulares AH, Yakovlev AG, Ivanova V, Stoica BA, Wang G, Iyer S and Smulson M: Role of poly(ADP-ribose) polymerase (PARP) cleavage in apoptosis. Caspase 3-resistant PARP mutant increases rates of apoptosis in transfected cells. J Biol Chem. 274:22932–22940. 1999. View Article : Google Scholar : PubMed/NCBI

29 

Shaulsky G, Ben-Ze'Ev A and Rotter V: Subcellular distribution of the p53 protein during the cell cycle of Balb/c 3T3 cells. Oncogene. 5:1707–1711. 1990.PubMed/NCBI

30 

Liao N, Sun L, Chen J, Zhong J, Zhang Y and Zhang R: A novel polysaccharide conjugate from Bullacta exarata induces G1-Phase arrest and apoptosis in human hepatocellular carcinoma HepG2 cells. Molecules. 22:3842017. View Article : Google Scholar

31 

Parrales A and Iwakuma T: Targeting oncogenic mutant p53 for Cancer Therapy. Front Oncol. 5:2882015. View Article : Google Scholar : PubMed/NCBI

32 

Aggarwal M, Saxena R, Sinclair E, Fu Y, Jacobs A, Dyba M, Wang X, Cruz I, Berry D, Kallakury B, et al: Reactivation of mutant p53 by a dietary-related compound phenethyl isothiocyanate inhibits tumor growth. Cell Death Differ. 23:1615–1627. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Zou Y, Huang Y and Ma X: Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells. Oncol Lett 18: 3358-3366, 2019.
APA
Zou, Y., Huang, Y., & Ma, X. (2019). Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells. Oncology Letters, 18, 3358-3366. https://doi.org/10.3892/ol.2019.10620
MLA
Zou, Y., Huang, Y., Ma, X."Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells". Oncology Letters 18.3 (2019): 3358-3366.
Chicago
Zou, Y., Huang, Y., Ma, X."Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells". Oncology Letters 18, no. 3 (2019): 3358-3366. https://doi.org/10.3892/ol.2019.10620
Copy and paste a formatted citation
x
Spandidos Publications style
Zou Y, Huang Y and Ma X: Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells. Oncol Lett 18: 3358-3366, 2019.
APA
Zou, Y., Huang, Y., & Ma, X. (2019). Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells. Oncology Letters, 18, 3358-3366. https://doi.org/10.3892/ol.2019.10620
MLA
Zou, Y., Huang, Y., Ma, X."Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells". Oncology Letters 18.3 (2019): 3358-3366.
Chicago
Zou, Y., Huang, Y., Ma, X."Phenylhexyl isothiocyanate suppresses cell proliferation and promotes apoptosis via repairing mutant P53 in human myeloid leukemia M2 cells". Oncology Letters 18, no. 3 (2019): 3358-3366. https://doi.org/10.3892/ol.2019.10620
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