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Article

Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis

  • Authors:
    • Likun Liu
    • Cuicui Han
    • Haitao Yu
    • Wenbin Zhu
    • Hongxia Cui
    • Lihong Zheng
    • Chunjing Zhang
    • Liling Yue
  • View Affiliations / Copyright

    Affiliations: Research Institute of Medicine and Pharmacy, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Biology Genetics, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Clinical Pharmacology, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China, Department of Biochemistry, Qiqihar Medical University, Qiqihar, Heilongjiang 161006, P.R. China
  • Pages: 2807-2816
    |
    Published online on: April 12, 2018
       https://doi.org/10.3892/or.2018.6363
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Abstract

Chloroquine (CQ) has been revealed to exhibit antitumor activity in several human tumors including lung cancer as mono‑ or add‑on therapy. The antitumor effect of CQ appears to depend on the tumor type, stage and genetic context. Few studies have focused on the mechanism concerning the antitumor effect of CQ monotherapy and the cause and effect relationship among autophagy, apoptosis and CQ in human lung A549 cells. Therefore, the present study aimed to identify the antitumor effect of CQ monotherapy and analyze the possible mechanism. In the present study, we demonstrated that CQ suppressed human A549 cell growth in a dose‑ and time‑dependent manner. CQ‑mediated growth inhibition in A549 cells was characterized by the targeting of the PI3K/AKT pathway, thus, inducing mitochondria‑mediated apoptosis at relatively higher concentrations by downregulating Bcl‑2 expression, increasing the expression level of Bax, decreasing mitochondrial membrane potential, releasing cytochrome c from the mitochondria into the cytosol, activating caspase‑3 and cleaving PARP. Collectively, these findings may offer a new rationale for using CQ as a lung cancer therapy drug in clinical practice.
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View References

1 

Homewood CA, Warhurst DC, Peters W and Baggaley VC: Lysosomes, pH and the anti-malarial action of chloroquine. Nature. 235:50–52. 1972. View Article : Google Scholar : PubMed/NCBI

2 

Rainsford KD, Parke AL, Clifford-Rashotte M and Kean WF: Therapy and pharmacological properties of hydroxychloroquine and chloroquine in treatment of systemic lupus erythematosus, rheumatoid and related diseases. Inflammopharmacology. 23:231–269. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Savarino A, Di Trani L, Donatelli I, Cauda R and Cassone A: New insights into the antiviral effects of chloroquine. Lancet Infect Dis. 6:67–69. 2006. View Article : Google Scholar : PubMed/NCBI

4 

Poole B and Ohkuma S: Effect of weak bases on the intralysosomal pH in mouse peritoneal macrophages. J Cell Biol. 90:665–669. 1981. View Article : Google Scholar : PubMed/NCBI

5 

Kim SH, Kim JH and Fried J: Enhancement of the radiation response of cultured tumor cells by chloroquine. Cancer. 32:536–540. 1973. View Article : Google Scholar : PubMed/NCBI

6 

Djordjevic B, Lange CS, Austin JP and Rotman M: Potentiation of radiation lethality in HeLa cells by combined mild hyperthermia and chloroquine. Radiat Res. 130:267–270. 1992. View Article : Google Scholar : PubMed/NCBI

7 

Djordevic B, Lange CS and Rotman M: Potentiation of radiation lethality in mouse melanoma cells by mild hyperthermia and chloroquine. Melanoma Res. 2:321–326. 1992. View Article : Google Scholar : PubMed/NCBI

8 

Zinn RL, Gardner EE, Dobromilskaya L, Murphy S, Marchionni L, Hann CL and Rudin CM: Combination treatment with ABT-737 and chloroquine in preclinical models of small cell lung cancer. Mol Cancer. 12:162013. View Article : Google Scholar : PubMed/NCBI

9 

Sasaki K, Tsuno NH, Sunami E, Tsurita G, Kawai K, Okaji Y, Nishikawa T, Shuno Y, Hongo K, Hiyoshi M, Kaneko M, et al: Chloroquine potentiates the anti-cancer effect of 5-fluorouracil on colon cancer cells. BMC Cancer. 10:3702010. View Article : Google Scholar : PubMed/NCBI

10 

Enzenmüller S, Gonzalez P, Debatin KM and Fulda S: Chloroquine overcomes resistance of lung carcinoma cells to the dual PI3K/mTOR inhibitor PI103 by lysosome-mediated apoptosis. Anticancer Drugs. 24:14–19. 2013. View Article : Google Scholar : PubMed/NCBI

11 

Yang S, Wang X, Contino G, Liesa M, Sahin E, Ying H, Bause A, Li Y, Stommel JM, Dell'antonio G, et al: Pancreatic cancers require autophagy for tumor growth. Genes Dev. 25:717–729. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Fan C, Wang W, Zhao B, Zhang S and Miao J: Chloroquine inhibits cell growth and induces cell death in A549 lung cancer cells. Bioorg Med Chem. 14:3218–3222. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Zheng Y, Zhao Y, Deng X, Yang S, Mao Y, Li Z, Jiang P, Zhao X and Wei Y: Chloroquine inhibits colon cancer cell growth in vitro and tumor growth in vivo via induction of apoptosis. Cancer Invest. 27:286–292. 2009. View Article : Google Scholar : PubMed/NCBI

14 

Jiang PD, Zhao YL, Yang SY, Mao YQ, Zheng YZ, Li ZG and Wei YQ: Effects of chloroquine diphosphate on proliferation and apoptosis of human leukemic K562 cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 16:768–771. 2008.(In Chinese). PubMed/NCBI

15 

Hu T, Li P, Luo Z, Chen X, Zhang J, Wang C, Chen P and Dong Z: Chloroquine inhibits hepatocellular carcinoma cell growth in vitro and in vivo. Oncol Rep. 35:43–49. 2016. View Article : Google Scholar : PubMed/NCBI

16 

Kim EL, Wüstenberg R, Rübsam A, Schmitz-Salue C, Warnecke G, Bücker EM, Pettkus N, Speidel D, Rohde V, Schulz-Schaeffer W, et al: Chloroquine activates the p53 pathway and induces apoptosis in human glioma cells. Neruo-Oncol. 12:389–400. 2010. View Article : Google Scholar

17 

Lakhter AJ, Sahu RP, Sun Y, Kaufmann WK, Androphy EJ, Travers JB and Naidu SR: Chloroquine promotes apoptosis in melanoma cells by inhibiting BH3 domain-mediated PUMA degradation. J Invest Dermatol. 133:2247–2254. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Mizushima N, Yoshimori T and Levine B: Methods in mammalian autophagy research. Cell. 140:313–326. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Maiuri MC, Zalckvar E, Kimchi A and Kroemer G: Self-eating and self-killing: Crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol. 8:741–752. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Kroemer G and Levine B: Autophagic cell death: The story of a misnomer. Nat Rev Mol Cell Biol. 9:1004–1010. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Kaminskyy V, Abdi A and Zhivotovsky B: A quantitative assay for the monitoring of autophagosome accumulation in different phases of the cell cycle. Autophagy. 7:83–90. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Yan Y, Jiang K, Liu P, Zhang X, Dong X, Gao J, Liu Q, Barr MP, Zhang Q, Hou X, Meng S and Gong P: Bafilomycin A1 induces caspase-independent cell death in hepatocellular carcinoma cells via targeting of autophagy and MAPK pathways. Sci Rep. 6:370522016. View Article : Google Scholar : PubMed/NCBI

23 

Wang L, Gao C, Yao S and Xie S: Blocking autophagic flux enhances matrine-induced apoptosis in human hepatoma cells. Int J Mol Sci. 14:23212–23230. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Sheppard KE, Kinross KM, Solomon B, Pearson RB and Phillips WA: Targeting PI3 kinase/Akt/mTOR signaling in cancer. Crit Rev Oncog. 17:69–95. 2012. View Article : Google Scholar : PubMed/NCBI

25 

Liu K, Liu P, Liu R and Wu X: Dual AO/EB staining to detect apoptosis in osteosarcoma cells compared with flow cytometry. Med Sci Monit Basic Res. 21:15–20. 2015. View Article : Google Scholar : PubMed/NCBI

26 

Zhao X, Ma S, Liu N, Liu J and Wang W: A polysaccharide from Trametes robiniophila Murrill induces apoptosis through intrinsic mitochondrial pathway in human osteosarcoma (U-2 OS) cells. Tumor Biol. 36:5255–5263. 2015. View Article : Google Scholar

27 

Thomé R, Lopes SC, Costa FT and Verinaud L: Chloroquine: Modes of action of an undervalued drug. Immunol Lett. 153:50–57. 2013. View Article : Google Scholar : PubMed/NCBI

28 

Zhao XG, Sun RJ, Yang XY, Liu DY, Lei DP, Jin T and Pan XL: Chloroquine-enhanced efficacy of cisplatin in the treatment of hypopharyngeal carcinoma in xenograft mice. PLoS One. 10:e01261472015. View Article : Google Scholar : PubMed/NCBI

29 

Yue L, Mei Q, Zhe W, Zhang W, Liu D and Liu Y: Study of chloroquine on anti-tumor effects of S180 tumor-bearing mice and its mechanisms. Acta Anatomica Sinica. 6:779–784. 2016.

30 

Mizushima N: Methods for monitoring autophagy. Int J Biochem Cell Biol. 36:2491–2502. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Kang R, Zeh HJ, Lotze MT and Tang D: The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ. 18:571–580. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Maiuri MC, Criollo A and Kroemer G: Crosstalk between apoptosis and autophagy within the Beclin 1 interactome. EMBO J. 29:515–516. 2010. View Article : Google Scholar : PubMed/NCBI

33 

Heras-Sandoval D, Pérez-Rojas JM, Hernández-Damián J and Pedraza-Chaverri J: The role of PI3K/AKT/mTOR pathway in the modulation of autophagy and the clearance of protein aggregates in neurodegeneration. Cell Signal. 26:2694–2701. 2014. View Article : Google Scholar : PubMed/NCBI

34 

Datta K, Suman S and Fornace AJ Jr: Radiation persistently promoted oxidative stress, activated mTOR via PI3K/Akt, and downregulated autophagy pathway in mouse intestine. Int J Biochem Cell Biol. 57:167–176. 2014. View Article : Google Scholar : PubMed/NCBI

35 

Mariño G, Niso-Santano M, Baehrecke EH and Kroemer G: Self-consumption: The interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol. 15:81–94. 2014. View Article : Google Scholar : PubMed/NCBI

36 

Yue Z and Zhong Y: From a global view to focused examination: Understanding cellular function of lipid kinase VPS34-Beclin 1 complex in autophagy. J Mol Cell Biol. 2:305–307. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Ciechomska IA, Goemans GC, Skepper JN and Tolkovsky AM: Bcl-2 complexed with Beclin-1 maintains full anti-apoptotic function. Oncogene. 28:2128–2141. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu L, Han C, Yu H, Zhu W, Cui H, Zheng L, Zhang C and Yue L: Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis. Oncol Rep 39: 2807-2816, 2018.
APA
Liu, L., Han, C., Yu, H., Zhu, W., Cui, H., Zheng, L. ... Yue, L. (2018). Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis. Oncology Reports, 39, 2807-2816. https://doi.org/10.3892/or.2018.6363
MLA
Liu, L., Han, C., Yu, H., Zhu, W., Cui, H., Zheng, L., Zhang, C., Yue, L."Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis". Oncology Reports 39.6 (2018): 2807-2816.
Chicago
Liu, L., Han, C., Yu, H., Zhu, W., Cui, H., Zheng, L., Zhang, C., Yue, L."Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis". Oncology Reports 39, no. 6 (2018): 2807-2816. https://doi.org/10.3892/or.2018.6363
Copy and paste a formatted citation
x
Spandidos Publications style
Liu L, Han C, Yu H, Zhu W, Cui H, Zheng L, Zhang C and Yue L: Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis. Oncol Rep 39: 2807-2816, 2018.
APA
Liu, L., Han, C., Yu, H., Zhu, W., Cui, H., Zheng, L. ... Yue, L. (2018). Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis. Oncology Reports, 39, 2807-2816. https://doi.org/10.3892/or.2018.6363
MLA
Liu, L., Han, C., Yu, H., Zhu, W., Cui, H., Zheng, L., Zhang, C., Yue, L."Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis". Oncology Reports 39.6 (2018): 2807-2816.
Chicago
Liu, L., Han, C., Yu, H., Zhu, W., Cui, H., Zheng, L., Zhang, C., Yue, L."Chloroquine inhibits cell growth in human A549 lung cancer cells by blocking autophagy and inducing mitochondrial‑mediated apoptosis". Oncology Reports 39, no. 6 (2018): 2807-2816. https://doi.org/10.3892/or.2018.6363
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