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Article

Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells

  • Authors:
    • Yoon‑Jin Lee
    • Sang‑Han Lee
  • View Affiliations / Copyright

    Affiliations: Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan 330‑930, Republic of Korea
  • Pages: 2133-2141
    |
    Published online on: June 15, 2017
       https://doi.org/10.3892/mmr.2017.6789
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Abstract

Sulforaphane (SFN) is an isothiocyanate compound derived from glucoraphanin, which is found in cruciferous vegetables, and has been heralded as a chemopreventive and/or chemotherapeutic agent. The present study investigated the effects of SFN on enhancing the anticancer role of cisplatin (cis-dichlorodiammineplatinum; CDDP) in H‑28 malignant mesothelioma cells. At concentrations demonstrating limited toxicity in MeT‑5A normal human mesothelial cells, combination treatment with the two compounds exhibited synergistic growth‑inhibiting and apoptosis‑promoting activities, as demonstrated by a series of proapoptotic events, including reactive oxygen species accumulation, loss of mitochondrial membrane potential, upregulation of p53 expression, increased B‑cell lymphoma 2 (Bcl‑2) associated X protein/Bcl‑2 ratio, activation of caspase‑3, the occurrence of a sub‑G0/G1 peak and an increase in cells with pyknotic and fragmented nuclei, Annexin V‑phycoerythrin‑positive staining and G2/M phase‑transition delay in the cell cycle. The phosphorylation levels of Akt and mammalian target of rapamycin were reduced by the combination treatment, which was accompanied by a significant increase in the level of autophagosomal marker protein microtubule‑associated protein 1 light chain 3B‑II and the accumulation of acidic vesicular organelles. Pretreatment with the antioxidant N‑acetylcysteine attenuated both apoptosis and autophagy, whereas inhibition of autophagy by bafilomycin A1 potentiated apoptotic cell death following the combination treatment with SFN and CDDP. Considering the pro‑oxidant‑based combinational approach, the results of the present study provide a rationale for targeting cytoprotective autophagy as a potential therapeutic strategy for malignant mesothelioma.
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1 

Wolff H, Vehmas T, Oksa P, Rantanen J and Vainio H: Asbestos, asbestosis, and cancer, the helsinki criteria for diagnosis and attribution 2014: Recommendations. Scand J Work Environ Health. 41:5–15. 2015. View Article : Google Scholar : PubMed/NCBI

2 

Raptopoulos V: Peritoneal mesothelioma. Crit Rev Diagn Imaging. 24:293–328. 1985.PubMed/NCBI

3 

Scripcariu V, Dajbog E, Radu I, Ferariu D, Pricop A, Grigoraş M and Dragomir C: Malignant peritoneal mesothelioma tumours. Evolution, treatment, prognosis: Rev Med Chir Soc Med Nat Iasi. 111:673–677. 2007.

4 

Ray M and Kindler HL: Malignant pleural mesothelioma: An update on biomarkers and treatment. Chest. 136:888–896. 2009. View Article : Google Scholar : PubMed/NCBI

5 

Villanova F, Procopio A and Rippo MR: Malignant mesothelioma resistance to apoptosis: Recent discoveries and their implication for effective therapeutic strategies. Curr Med Chem. 15:631–641. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P, Gatzemeier U, Boyer M, Emri S, Manegold C, et al: Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol. 21:2636–2644. 2003. View Article : Google Scholar : PubMed/NCBI

7 

Tomczyk J and Olejnik A: Sulforaphane-a possible agent in prevention and therapy of cancer. Postepy Hig Med Dosw (Online). 64:590–603. 2010.(In Polish). PubMed/NCBI

8 

Lin LC, Yeh CT, Kuo CC, Lee CM, Yen GC, Wang LS, Wu CH, Yang WC and Wu AT: Sulforaphane potentiates the efficacy of imatinib against chronic leukemia cancer stem cells through enhanced abrogation of Wnt/β-catenin function. J Agric Food Chem. 60:7031–7039. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Kim H, Kim EH, Eom YW, Kim WH, Kwon TK, Lee SJ and Choi KS: Sulforaphane sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-resistant hepatoma cells to TRAIL-induced apoptosis through reactive oxygen species-mediated up-regulation of DR5. Cancer Res. 66:1740–1750. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Sharma K, Le N, Alotaibi M and Gewirtz DA: Cytotoxic autophagy in cancer therapy. Int J Mol Sci. 15:10034–10051. 2014. View Article : Google Scholar : PubMed/NCBI

11 

Giuliani CM and Dass CR: Metabolic stress and cancer: Is autophagy the common denominator and a feasible target? J Pharm Pharmacol. 66:597–614. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Vlahopoulos S, Critselis E, Voutsas IF, Perez SA, Moschovi M, Baxevanis CN and Chrousos GP: New use for old drugs? Prospective targets of chloroquines in cancer therapy. Curr Drug Targets. 15:843–851. 2014. View Article : Google Scholar : PubMed/NCBI

13 

Jin S and White E: Role of autophagy in cancer: Management of metabolic stress. Autophagy. 3:28–31. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Chou TC and Talalay P: Quantitative analysis of dose-effect relationships: The combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul. 22:27–55. 1984. View Article : Google Scholar : PubMed/NCBI

15 

Mehlen P and Thibert C: Dependence receptors: Between life and death. Cell Mol Life Sci. 61:1854–1866. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Siddik ZH: Cisplatin: Mode of cytotoxic action and molecular basis of resistance. Oncogene. 22:7265–7279. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Chen H, Landen CN, Li Y, Alvarez RD and Tollefsbol TO: Enhancement of cisplatin-mediated apoptosis in ovarian cancer cells through potentiating G2/M arrest and p21 upregulation by combinatorial epigallocatechin gallate and sulforaphane. J Oncol. 2013:8729572013. View Article : Google Scholar : PubMed/NCBI

18 

Singh SV, Herman-Antosiewicz A, Singh AV, Lew KL, Srivastava SK, Kamath R, Brown KD, Zhang L and Baskaran R: Sulforaphane-induced G2/M phase cell cycle arrest involves checkpoint kinase 2-mediated phosphorylation of cell division cycle 25C. J Biol Chem. 279:25813–25822. 2004. View Article : Google Scholar : PubMed/NCBI

19 

Deavall DG, Martin EA, Horner JM and Roberts R: Drug-induced oxidative stress and toxicity. J Toxicol. 2012:6454602012. View Article : Google Scholar : PubMed/NCBI

20 

Deng S, Tang S, Zhang S, Zhang C, Wang C, Zhou Y, Dai C and Xiao X: Furazolidone induces apoptosis through activating reactive oxygen species-dependent mitochondrial signaling pathway and suppressing PI3K/Akt signaling pathway in HepG2 cells. Food Chem Toxicol. 75:173–186. 2015. View Article : Google Scholar : PubMed/NCBI

21 

Dunlop EA and Tee AR: mTOR and autophagy: A dynamic relationship governed by nutrients and energy. Semin Cell Dev Biol. 36:121–129. 2014. View Article : Google Scholar : PubMed/NCBI

22 

Nazio F and Cecconi F: mTOR, AMBRA1, and autophagy: An intricate relationship. Cell Cycle. 12:2524–2525. 2013. View Article : Google Scholar : PubMed/NCBI

23 

Chen B, Li D, Li M, Li S, Peng K, Shi X, Zhou L, Zhang P, Xu Z, Yin H, et al: Induction of mitochondria-mediated apoptosis and PI3K/Akt/ mTOR-mediated autophagy by aflatoxin B2 in hepatocytes of broilers. Oncotarget. 7:84989–84998. 2016.PubMed/NCBI

24 

Mi S, Xiang G, Yuwen D, Gao J, Guo W, Wu X, Wu X, Sun Y, Su Y, Shen Y and Xu Q: Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway. Toxicol Appl Pharmacol. 310:78–86. 2016. View Article : Google Scholar : PubMed/NCBI

25 

Zhou S, Liu L, Li H, Eilers G, Kuang Y, Shi S, Yan Z, Li X, Corson JM, Meng F, et al: Multipoint targeting of the PI3K/mTOR pathway in mesothelioma. Br J Cancer. 110:2479–2488. 2014. View Article : Google Scholar : PubMed/NCBI

26 

Echeverry N, Ziltener G, Barbone D, Weder W, Stahel PA, Broaddus VC and Felley-Bosco E: Inhibition of autophagy sensitizes malignant pleural mesothelioma cells to dual PI3K/mTOR inhibitors. Cell Death Dis. 6:e17572015. View Article : Google Scholar : PubMed/NCBI

27 

Zhao GX, Pan H, Ouyang DY and He XH: The critical molecular interconnections in regulating apoptosis and autophagy. Ann Med. 47:305–315. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Lu Z, Luo RZ, Lu Y, Zhang X, Yu Q, Khare S, Kondo S, Kondo Y, Yu Y, Mills GB, et al: The tumor suppressor gene ARHI regulates autophagy and tumor dormancy in human ovarian cancer cells. J Clin Invest. 118:3917–3929. 2008.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Lee YJ and Lee SH: Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells. Mol Med Rep 16: 2133-2141, 2017.
APA
Lee, Y., & Lee, S. (2017). Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells. Molecular Medicine Reports, 16, 2133-2141. https://doi.org/10.3892/mmr.2017.6789
MLA
Lee, Y., Lee, S."Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells". Molecular Medicine Reports 16.2 (2017): 2133-2141.
Chicago
Lee, Y., Lee, S."Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells". Molecular Medicine Reports 16, no. 2 (2017): 2133-2141. https://doi.org/10.3892/mmr.2017.6789
Copy and paste a formatted citation
x
Spandidos Publications style
Lee YJ and Lee SH: Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells. Mol Med Rep 16: 2133-2141, 2017.
APA
Lee, Y., & Lee, S. (2017). Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells. Molecular Medicine Reports, 16, 2133-2141. https://doi.org/10.3892/mmr.2017.6789
MLA
Lee, Y., Lee, S."Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells". Molecular Medicine Reports 16.2 (2017): 2133-2141.
Chicago
Lee, Y., Lee, S."Pro-oxidant activity of sulforaphane and cisplatin potentiates apoptosis and simultaneously promotes autophagy in malignant mesothelioma cells". Molecular Medicine Reports 16, no. 2 (2017): 2133-2141. https://doi.org/10.3892/mmr.2017.6789
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