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Allyl Isothiocyanate Induces Cell Toxicity by Multiple Pathways in Human Breast Cancer Cells

    https://doi.org/10.1142/S0192415X16500245Cited by:14
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    Abstract

    Isothiocyanates (ITCs) occur in many cruciferous vegetables. These compounds, which have significant anticancer actions, can induce apoptosis in different human cancer cell lines. In the present study, we investigated if allyl isothiocyanate (AITC) would induce toxicity in human breast cancer MCF-7 (estrogen receptor positive) and MDA-MB-231 (estrogen receptor negative) cells. We found that AITC stimulated reactive oxygen species and Ca2+ production, and decreased the mitochondrial membrane potential. Activity of caspase-8, -9 and -3 was increased by AITC in both cell lines. AITC also induced mitochondrial-mediated apoptosis, as shown by cytochrome c, AIF and Endo G release from mitochondria, activation of caspase-9 and caspase-3, and formation of DAPI-positive cells. There was a significant reduction in the levels of the anti-apoptotic protein Bcl-2 along with a marked increase in the pro-apoptotic protein Bax in both cell lines. AITC induced apoptosis in human breast cancer MCF-7 cells via AIF and Endo G signaling pathways, but in MDA-MB-231 cells apoptosis occurred via the GADD153 pathway. This study has revealed novel anti-cancer mechanisms of AITC, a compound that is ordinarily present in human diets and may have potential therapeutic effects in various cancers.

    References

    • Bhattacharya, A., Y. Li, F. Geng, R. Munday and Y. Zhang. [2012] The principal urinary metabolite of allyl isothiocyanate, N-acetyl-S-(N-allylthiocarbamoyl)cysteine, inhibits the growth and muscle invasion of bladder cancer. Carcinogenesis 33, 394–398. Crossref, Medline, ISI, Google Scholar
    • Chen, N.G., K.T. Chen, C.C. Lu, Y.H. Lan, C.H. Lai, Y.T. Chung, J.S. Yang and Y.C. Lin. [2010] Allyl isothiocyanate triggers G2/M phase arrest and apoptosis in human brain malignant glioma gbm 8401 cells through a mitochondria-dependent pathway. Oncol. Rep. 24, 449–455. Medline, ISI, Google Scholar
    • Chen, Y.L., F.S. Chueh, J.S. Yang, S.C. Hsueh, C.C. Lu, J.H. Chiang, C.S. Lee, H.F. Lu and J.G. Chung. [2014] Antitumor effects with apoptotic death in human promyelocytic leukemia Hl-60 cells and suppression of leukemia Xenograft tumor growth by irinotecan HCl. Environ. Toxicol. ISI, Google Scholar
    • Chiu, C.H., Y.C. Chou, J.P. Lin, C.L. Kuo, H.F. Lu, Y.P. Huang, C.C. Yu, M.L. Lin and J.G. Chung. [2015] Chloroform extract of Solanum lyratum induced G0/G1 arrest via p21/p16 and induced apoptosis via reactive oxygen species, caspases and mitochondrial pathways in human oral cancer cell lines. Am. J. Chin. Med. 1–17. Medline, ISI, Google Scholar
    • Comelli, M., N. Genero and I. Mavelli. [2009] Caspase-independent apoptosis in friend’s erythroleukemia cells: Role of mitochondrial ATP synthesis impairment in relocation of apoptosis-inducing factor and endonuclease G. J. Bioenerg. Biomembr. 41, 49–59. Crossref, Medline, ISI, Google Scholar
    • Fahey, J.W., A.T. Zalcmann and P. Talalay. [2001] The chemical diversity and distribution of glucosinolates and isothiocyanates among plants. Phytochemistry 56, 5–51. Crossref, Medline, ISI, Google Scholar
    • Fan, L., Y. Zheng, K.D. Yu, G.Y. Liu, J. Wu, J.S. Lu, K.W. Shen, Z.Z. Shen and Z.M. Shao. [2009] Breast cancer in a transitional society over 18 years: Trends and present status in Shanghai, China. Breast Cancer Res. Treat. 117, 409–416. Crossref, Medline, ISI, Google Scholar
    • Geng, F., L. Tang, Y. Li, L. Yang, K.S. Choi, A.L. Kazim and Y. Zhang. [2011] Allyl isothiocyanate arrests cancer cells in mitosis, and mitotic arrest in turn leads to apoptosis via Bcl-2 protein phosphorylation. J. Biol. Chem. 286, 32259–32267. Crossref, Medline, ISI, Google Scholar
    • Green, D.R. and J.C. Reed. [1998] Mitochondria and apoptosis. Science 281, 1309–1312. Crossref, Medline, ISI, Google Scholar
    • Green, D.R. and G.I. Evan. [2002] A matter of life and death. Cancer Cell 1, 19–30. Crossref, Medline, ISI, Google Scholar
    • Hasegawa, T., H. Nishino and A. Iwashima. [1993] Isothiocyanates inhibit cell cycle progression of Hela cells at G2/M phase. Anticancer Drugs 4, 273–279. Crossref, Medline, ISI, Google Scholar
    • Hsia, T.C., J.H. Lin, S.C. Hsu, N.Y. Tang, H.F. Lu, S.H. Wu, J.G. Lin and J.G. Chung. [2015] Cantharidin induces DNA damage and inhibits DNA repair-associated protein levels in Nci-H460 human lung cancer cells. Environ. Toxicol. 30, 1135–1143. Crossref, Medline, ISI, Google Scholar
    • Hsieh, L.C., S.L. Hsieh, C.T. Chen, J.G. Chung, J.J. Wang and C.C. Wu. [2015] Induction of alpha-phellandrene on autophagy in human liver tumor cells. Am. J. Chin. Med. 43, 121–136. Link, ISI, Google Scholar
    • Hu, W. and J.J. Kavanagh. [2003] Anticancer therapy targeting the apoptotic pathway. Lancet Oncol. 4, 721–729. Crossref, Medline, ISI, Google Scholar
    • Hwang, E.S. and H.J. Lee. [2006] Allyl isothiocyanate and its N-acetylcysteine conjugate suppress metastasis via inhibition of invasion, migration, and matrix metalloproteinase-2/-9 activities in SK-Hep 1 human hepatoma cells. Exp. Biol. Med. 231, 421–430. Crossref, ISI, Google Scholar
    • Jemal, A., F. Bray, M. Center, J. Ferlay, E. Ward and D. Forman. [2011] Global cancer statistics. CA Cancer J. Clin. 61, 69–90. Crossref, Medline, ISI, Google Scholar
    • Kagawa, S., J. Gu, T. Honda, T.J. McDonnell, S.G. Swisher, J.A. Roth and B. Fang. [2001] Deficiency of caspase-3 in Mcf7 cells blocks Bax-mediated nuclear fragmentation but not cell death. Clin. Cancer Res. 7, 1474–1480. Medline, ISI, Google Scholar
    • Kumar, A., S.S. D’Souza, S. Tickoo, B.P. Salimath and H.B. Singh. [2009] Antiangiogenic and proapoptotic activities of allyl isothiocyanate inhibit ascites tumor growth in vivo. Integr. Cancer Ther. 8, 75–87. Crossref, Medline, ISI, Google Scholar
    • Kumar, S. [2007] Caspase function in programmed cell death. Cell Death Differ. 14, 32–43. Crossref, Medline, ISI, Google Scholar
    • Kushad, M.M., A.F. Brown, A.C. Kurilich, J.A. Juvik, B.P. Klein, M.A. Wallig and E.H. Jeffery. [1999] Variation of glucosinolates in vegetable crops of brassica oleracea. J. Agric. Food Chem. 47, 1541–1548. Crossref, Medline, ISI, Google Scholar
    • Lau, W.S., T. Chen and Y.S. Wong. [2010] Allyl isothiocyanate induces G2/M arrest in human colorectal adenocarcinoma SW620 cells through down-regulation of cdc25b and cdc25c. Mol. Med. Rep. 3, 1023–1030. Medline, ISI, Google Scholar
    • Lin, Y.T., A.C. Huang, C.L. Kuo, J.S. Yang, Y.H. Lan, C.C. Yu, W.W. Huang and J.G. Chung. [2013] Induction of cell cycle arrest and apoptosis in human osteosarcoma U-2 OS cells by Solanum lyratum extracts. Nutr. Cancer 65, 469–479. Crossref, Medline, ISI, Google Scholar
    • Liu, K.C., C.Y. Yen, R.S. Wu, J.S. Yang, H.F. Lu, K.W. Lu, C. Lo, H.Y. Chen, N.Y. Tang, C.C. Wu and J.G. Chung. [2014] The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin-mediated cell death of human prostate cancer PC-3 cells. Environ. Toxicol. 29, 428–439. Crossref, Medline, ISI, Google Scholar
    • Liu, Y., Q.F. Shi, M. Qi, S. Tashiro, S. Onodera and T. Ikejima. [2012] Interruption of hepatocyte growth factor signaling augmented oridonin-induced death in human non-small cell lung cancer A549 cells via c-met-nuclear factor-κb-cyclooxygenase-2 and c-met-bcl-2-caspase-3 pathways. Biol. Pharm. Bull. 35, 1150–1158. Crossref, Medline, ISI, Google Scholar
    • Rao, R.V., H.M. Ellerby and D.E. Bredesen. [2004] Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 11, 372–380. Crossref, Medline, ISI, Google Scholar
    • Ricci, J.E., C. Munoz-Pinedo, P. Fitzgerald, B. Bailly-Maitre, G.A. Perkins, N. Yadava, I.E. Scheffler, M.H. Ellisman and D.R. Green. [2004] Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex i of the electron transport chain. Cell 117, 773–786. Crossref, Medline, ISI, Google Scholar
    • Rojas, C., B. Pan-Castillo, C. Valls, G. Pujadas, S. Garcia-Vallve, L. Arola and M. Mulero. [2014] Resveratrol enhances palmitate-induced er stress and apoptosis in cancer cells. PloS One 9, e113929. Crossref, Medline, ISI, Google Scholar
    • Rungapamestry, V., A.J. Duncan, Z. Fuller and B. Ratcliffe. [2006] Changes in glucosinolate concentrations, myrosinase activity, and production of metabolites of glucosinolates in cabbage (Brassica oleracea var. capitata) cooked for different durations. J. Agric. Food Chem. 54, 7628–7634. Crossref, Medline, ISI, Google Scholar
    • Saelens, X., N. Festjens, L. Vande Walle, M. van Gurp, G. van Loo and P. Vandenabeele. [2004] Toxic proteins released from mitochondria in cell death. Oncogene 23, 2861–2874. Crossref, Medline, ISI, Google Scholar
    • Sellam, A., A. Dongo, T. Guillemette, P. Hudhomme and P. Simoneau. [2007] Transcriptional responses to exposure to the brassicaceous defence metabolites camalexin and allyl-isothiocyanate in the necrotrophic fungus Alternaria brassicicola. Mol. Plant Pathol. 8, 195–208. Crossref, Medline, ISI, Google Scholar
    • Smith, T.K., E.K. Lund, M.L. Parker, R.G. Clarke and I.T. Johnson. [2004] Allyl-isothiocyanate causes mitotic block, loss of cell adhesion and disrupted cytoskeletal structure in HT29 cells. Carcinogenesis 25, 1409–1415. Crossref, Medline, ISI, Google Scholar
    • Srivastava, S.K., D. Xiao, K.L. Lew, P. Hershberger, D.M. Kokkinakis, C.S. Johnson, D.L. Trump and S.V. Singh. [2003] Allyl isothiocyanate, a constituent of cruciferous vegetables, inhibits growth of PC-3 human prostate cancer xenografts in vivo. Carcinogenesis 24, 1665–1670. Crossref, Medline, ISI, Google Scholar
    • Thejass, P. and G. Kuttan. [2007] Allyl isothiocyanate (aitc) and phenyl isothiocyanate (pitc) inhibit tumour-specific angiogenesis by downregulating nitric oxide (no) and tumour necrosis factor-α (tnf-α) production. Nitric. Oxide. 16, 247–257. Crossref, Medline, ISI, Google Scholar
    • Uematsu, Y., K. Hirata, K. Suzuki, K. Iida, T. Ueta and K. Kamata. [2002] Determination of isothiocyanates and related compounds in mustard extract and horseradish extract used as natural food additives. Shokuhin Eiseigaku Zasshi 43, 10–17. Crossref, Medline, Google Scholar
    • Wagner, A.E., C. Boesch-Saadatmandi, J. Dose, G. Schultheiss and G. Rimbach. [2012] Anti-inflammatory potential of allyl-isothiocyanate — role of nrf2, nf-(κ) b and microrna-155. J. Cell. Mol. Med. 16, 836–843. Crossref, Medline, ISI, Google Scholar
    • Wajant, H. [2002] The Fas signaling pathway: More than a paradigm. Science 296, 1635–1636. Crossref, Medline, ISI, Google Scholar
    • Wang, J., A. Wu, Y. Xu, J. Liu and X. Qian. [2009] M(2)-a induces apoptosis and G(2)-M arrest via inhibiting Pi3k/Akt pathway in HL60 cells. Cancer Lett. 283, 193–202. Crossref, Medline, ISI, Google Scholar
    • Wilson, M.R. [1998] Apoptotic signal transduction: Emerging pathways. Biochem. Cell Biol. 76, 573–582. Crossref, Medline, ISI, Google Scholar
    • Wu, L.Y., H.F. Lu, Y.C. Chou, Y.L. Shih, D.T. Bau, J.C. Chen, S.C. Hsu and J.G. Chung. [2015] Kaempferol induces DNA damage and inhibits DNA repair associated protein expressions in human promyelocytic leukemia HL-60 cells. Am. J. Chin. Med. 43, 365–382. Link, ISI, Google Scholar
    • Wu, S.H., T.Y. Wu, Y.T. Hsiao, J.H. Lin, S.C. Hsu, T.C. Hsia, S.T. Yang, W.H. Hsu and J.G. Chung. [2014] Bufalin induces cell death in human lung cancer cells through disruption of DNA damage response pathways. Am. J. Chin. Med. 42, 729–742. Link, ISI, Google Scholar
    • Xu, G. and Y. Shi. [2007] Apoptosis signaling pathways and lymphocyte homeostasis. Cell Res. 17, 759–771. Crossref, Medline, ISI, Google Scholar
    • Zhang, Y., L. Tang and V. Gonzalez. [2003] Selected isothiocyanates rapidly induce growth inhibition of cancer cells. Mol. Cancer Ther. 2, 1045–1052. Medline, ISI, Google Scholar
    • Zhang, Y. [2010] Allyl isothiocyanate as a cancer chemopreventive phytochemical. Mol. Nutr. Food Res. 54, 127–135. Crossref, Medline, ISI, Google Scholar
    • Zhang, Y.H., Y.L. Wu, S. Tashiro, S. Onodera and T. Ikejima. [2011] Reactive oxygen species contribute to oridonin-induced apoptosis and autophagy in human cervical carcinoma Hela cells. Acta Pharmacol. Sin. 32, 1266–1275. Crossref, Medline, ISI, Google Scholar
    Published: 1 April 2016
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