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Diallyl disulfide induces apoptosis and autophagy via mTOR pathway in myeloid leukemic cell line

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Tumor Biology

Abstract

Leukemia is a hematological malignancy which is produced by uncontrolled proliferation of leukocyte precursors. Currently, alternative medicines, using herb extracts, have been developed for cancer treatment. In this study, the effect of diallyl disulfide (DADS) on the induction of apoptosis and autophagy was investigated in K562 and NB4 myeloid leukemia cells. Leukemia cells were treated with various concentrations of DADS for 24 and 48 h. The percentage of cell viability was measured using an MTT assay. The percentages of apoptosis and autophagy were analyzed by staining with annexin-FITC and anti-LC3 FITC-conjugated antibodies, respectively. Then, the stained cells were detected by flow cytometry. In addition, PP242, a mammalian target rapamycin (mTOR) inhibitor, was used to study the involvement of the mTOR pathway in DADS-induced apoptosis and autophagy. mTOR mRNA expression was measured by real-time PCR. The results showed that DADS decreased cell viability and increased the percentage of cell apoptosis in a dose- and time-dependent manner. mTOR expression was significantly decreased in DADS- and mTOR inhibitor-treated cells. The highest percentages of apoptosis and autophagy were shown in cells treated with 100 μg/ml DADS combined with 10 μM of the mTOR inhibitor. According to our results, DADS could induce apoptosis and autophagy via the mTOR pathway in both K562 and NB4 myeloid leukemia cell lines.

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References

  1. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114:937–51.

    Article  CAS  PubMed  Google Scholar 

  2. Bellm LA, Epstein JB, Rose-Ped A, Martin P, Fuchs HJ. Patient reports of complications of bone marrow transplantation. Support Care Cancer. 2000;8:33–9.

    CAS  PubMed  Google Scholar 

  3. Huang S-T, Wang C-Y, Yang R-C, Chu C-J, Wu H-T, Pang J-HS. Wogonin, an active compound in Scutellaria baicalensis, induces apoptosis and reduces telomerase activity in the HL-60 leukemia cells. Phytomedicine. 2010;17:47–54.

    Article  CAS  PubMed  Google Scholar 

  4. Oommen S, Anto RJ, Srinivas G. Karunagaran D: allicin (from garlic) induces caspase-mediated apoptosis in cancer cells. Eur J Pharmacol. 2004;485:97–103.

    Article  CAS  PubMed  Google Scholar 

  5. Shukla Y, Kalra N. Cancer chemoprevention with garlic and its constituents. Cancer Lett. 2007;247:167–81.

    Article  CAS  PubMed  Google Scholar 

  6. Kwon KB, Yoo SJ, Ryu DG, Yang JY, Rho HW, Kim JS, et al. Induction of apoptosis by diallyl disulfide through activation of caspase-3 in human leukemia HL-60 cells. BiochemPharmacol. 2002;63:41–17.

    CAS  Google Scholar 

  7. Yang J-S, Kok L-F, Lin Y-H, Kuo T-C, Yang J-L, Lin C-C, et al. Diallyl disulfide inhibits WEHI-3 leukemia cells in vivo. Anticancer Res. 2006;26:219–25.

    CAS  PubMed  Google Scholar 

  8. Wen J, Zhang Y, Chen X, Shen L, Li GC, Xu M. Enhancement of diallyl disulfide-induced apoptosis by inhibitors of MAPKs in human HepG2 hepatoma cells. Biochem Pharmacol. 2004;68(2):323–31.

    Article  CAS  PubMed  Google Scholar 

  9. Shin DY, Kim G-Y, Lee JH, Choi BT, Yoo YH, Choi YH. Apoptosis induction of human prostate carcinoma DU145 cells by diallyl disulfide via modulation of JNK and PI3K/AKT signaling pathways. Int J Mol Sci. 2012;13:14158–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Chu Y-L, Ho C-T, Chung J-G, Raghu R, Lo Y-C, Sheen L-Y. Allicin induces anti-human liver cancer cells through the p53 gene modulating apoptosis and autophagy. J Agric Food Chem. 2013;1:9839–48.

    Article  Google Scholar 

  11. Chu YL, Ho CT, Chung JG, Rajasekaran R, Sheen LY. Allicin induces p53-mediated autophagy in Hep G2 human liver cancer cells. J Agric Food Chem. 2012;60:8363–71.

    Article  CAS  PubMed  Google Scholar 

  12. Wang L, Chen L, Yu M, HuiXu U, Cheng B, Lin YS, et al. Discovering new mTOR inhibitors for cancer treatment through virtual screening methods and in vitro assays. Sci Rep. 2016. doi:10.1038/srep18987.

    Google Scholar 

  13. Wang F, Liua Z, Zengc J, Zhud H, Lie J, Chenga X, et al. Metformin synergistically sensitizes FLT3-ITD-positive acute myeloid leukemia to sorafenib by promoting mTOR-mediated apoptosis and autophagy. Leuk Res. 2015;15:1421–7.

    Article  Google Scholar 

  14. Fornelli F, Leone A, Verdesca I, Minervini F, Zacheo G. The influence of lycopene on the proliferation of human breast cell line (MCF-7). Toxicol In Vitro. 2007;21:217–23.

    Article  CAS  PubMed  Google Scholar 

  15. Sadava D, Whitlock E, Kane SE. The green tea polyphenol, epigallocatechin-3-gallate inhibits telomerase and induces apoptosis in drug-resistant lung cancer cells. Biochem Biophys Res Commun. 2007;360:233–7.

    Article  CAS  PubMed  Google Scholar 

  16. Yu Z, Li W, Liu F. Inhibition of proliferation and induction of apoptosis by genistein in colon cancer HT-29 cells. Cancer Lett. 2004;215:159–66.

    Article  CAS  PubMed  Google Scholar 

  17. Dong M, Yang G, Liu H, Liu X, Lin S, Sun D, et al. Aged black garlic extract inhibits HT29 colon cancer cell growth via the PI3K/Akt signaling pathway. Biomed Rep. 2014;2:250–4.

    PubMed  PubMed Central  Google Scholar 

  18. Park C, Park S, Chung YH, Kim GY, Choi YW, Kim BW, et al. Induction of apoptosis by a hexane extract of aged black garlic in the human leukemic U937 cells. Nutr Res Pract. 2014;8:132–7.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Wu XJ, Kassie F, Mersch Sundermann V. Thee role of reactive oxygen species (ROS) production on diallyl disulfide (DADS) induced apoptosis and cell cycle arrest in human 549 lung carcinoma cells. Mutat Res. 2005;579:115–24.

    Article  CAS  PubMed  Google Scholar 

  20. Arunkumar A, Vijayababu MR, Gunadharini N, Krishnamoorthy G, Arunakaran J. Induction of apoptosis and histone hyperacetylation by diallyl disulfide in prostate cancer cell line PC-3. Cancer Lett. 2007;251:59–67.

    Article  CAS  PubMed  Google Scholar 

  21. Lu HF, Sue CC, Yu CS, Chen SC, Chen GW, Chung JG. Diallyl disulfide (DADS) induced apoptosis undergo caspase-3 activity in human bladder cancer T24 cells. Food Chem Toxicol. 2004;42:1543–52.

    Article  CAS  PubMed  Google Scholar 

  22. Wang N, Feng Y, Zhu M, Tsang C-M, Man K, TongYandTsao S-W. Berberine induces autophagic cell death and mitochondrial apoptosis in liver cancer cells: the cellular mechanism. J Cell Biochem. 2010;111:1426–36.

    Article  CAS  PubMed  Google Scholar 

  23. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149:274–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Asnaghi L, Bruno P, Priulla M, Nicolin A. mTOR: a protein kinase switching between life and death. Pharmacol Res. 2004;50:545–9.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was partially supported by National Research University (NRU), Mahidol University, Thailand.

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Correspondence to Dalina I. Tanyong.

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Suangtamai, T., Tanyong, D.I. Diallyl disulfide induces apoptosis and autophagy via mTOR pathway in myeloid leukemic cell line. Tumor Biol. 37, 10993–10999 (2016). https://doi.org/10.1007/s13277-016-4989-y

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  • DOI: https://doi.org/10.1007/s13277-016-4989-y

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