Chemotherapy

Anticancer Section / Original Paper

Lysosome Inhibitors Enhance the Chemotherapeutic Activity of Doxorubicin in HepG2 Cells

Li Y. · Sun Y. · Jing L. · Wang J. · Yan Y. · Feng Y. · Zhang Y. · Liu Z. · Ma L. · Diao A.

Author affiliations

School of Biotechnology, Tianjin University of Science and Technology, Key Laboratory of Industrial Fermentation Microbiology of the Ministry of Education, Tianjin, China

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Chemotherapy 2017;62:85-93

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Article / Publication Details

First-Page Preview
Abstract of Anticancer Section / Original Paper

Received: May 09, 2016
Accepted: July 29, 2016
Published online: October 21, 2016
Issue release date: February 2017

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE

Abstract

The lysosome inhibitors bafilomycin A1 and chloroquine have both lysosomotropic properties and autophagy inhibition ability, and are promising clinical agents to be used in combination with anticancer drugs. In order to investigate this combination effect, HepG2 cells were treated with bafilomycin A1, chloroquine, or/and doxorubicin, and their proliferative ability, induction of apoptosis, and the changes of lysosomal membrane permeabilization and mitochondrial membrane potential were studied. The results demonstrate that treatment with bafilomycin A1 or chloroquine alone at a relatively low concentration promotes the inhibitory effect of doxorubicin on cell growth and apoptosis. Further studies reveal that bafilomycin A1 and chloroquine promote lysosomal membrane permeabilization and the reduction of mitochondrial membrane potential induced by doxorubicin. Our findings suggest that bafilomycin A1 and chloroquine potentiate the anticancer effect of doxorubicin in hepatic cancer cells and that supplementation of conventional chemotherapy with lysosome inhibitors may provide a more efficient anticancer therapy.

© 2016 S. Karger AG, Basel




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References

  1. Brayfield A (ed): Martindale: The Complete Drug Reference. Pharmaceutical Press, 2014. Emerg Nurse 2014;22:12.
  2. Dudeck O, Ricke J: Advances in regional chemotherapy of the liver. Expert Opin Drug Deliv 2011;8:1057-1069.
  3. Chatterjee K, Zhang J, Honbo N, Karliner JS: Doxorubicin cardiomyopathy. Cardiology 2010;115:155-162.
  4. Klohs WD, Steinkampf RW: The effect of lysosomotropic agents and secretory inhibitors on anthracycline retention and activity in multiple drug-resistant cells. Mol Pharmacol 1988;34:180-185.
    External Resources
  5. Sehested M, Skovsgaard T, Roed H: The carboxylic ionophore monensin inhibits active drug efflux and modulates in vitro resistance in daunorubicin resistant Ehrlich ascites tumor cells. Biochem Pharmacol 1988;37:3305-3310.
  6. Miura N, Tanji N, Yanagihara Y, Noda T, Asai S, Nishimura K, Shirato A, Miyauchi Y, Kikugawa T, Yokoyama M: Low-dose docetaxel combined with dexamethasone is feasible for patients with castration-resistant prostate cancer. Chemotherapy 2015;61:23-31.
  7. Lavakhamseh H, Mohajeri P, Rouhi S, Shakib P, Ramazanzadeh R, Rasani A, Mansouri M: Multidrug-resistant Escherichia coli strains isolated from patients are associated with class 1 and 2 integrons. Chemotherapy 2016;61:72-76.
  8. Amaravadi RK, Thompson CB: The roles of therapy-induced autophagy and necrosis in cancer treatment. Clin Cancer Res 2007;13:7271-7279.
  9. Tasdemir E, Galluzzi L, Maiuri MC, Criollo A, Vitale I, Hangen E, Modjtahedi N, Kroemer G: Methods for assessing autophagy and autophagic cell death. Methods Mol Biol 2008;445:29-76.
  10. Solomon VR, Lee H: Chloroquine and its analogs: a new promise of an old drug for effective and safe cancer therapies. Eur J Pharmacol 2009;625:220-233.
  11. Yoshimori T, Yamamoto A, Moriyama Y, Futai M, Tashiro Y: Bafilomycin A1, a specific inhibitor of vacuolar-type H(+)-ATPase, inhibits acidification and protein degradation in lysosomes of cultured cells. J Biol Chem 1991;266:17707-17712.
    External Resources
  12. Moriyama Y, Nelson N: H+-translocating ATPase in Golgi apparatus. Characterization as vacuolar H+-ATPase and its subunit structures. J Biol Chem 1989;264:18445-18450.
    External Resources
  13. Yamamoto A, Tagawa Y, Yoshimori T, Moriyama Y, Masaki R, Tashiro Y: Bafilomycin A1 prevents maturation of autophagic vacuoles by inhibiting fusion between autophagosomes and lysosomes in rat hepatoma cell line, H-4-II-E cells. Cell Struct Funct 1998;23:33-42.
  14. Gao M, Xu Y, Qiu L: Sensitization of multidrug-resistant malignant cells by liposomes co-encapsulating doxorubicin and chloroquine through autophagic inhibition. J Liposome Res 2016, Epub ahead of print.
  15. Dirks-Naylor AJ: The role of autophagy in doxorubicin-induced cardiotoxicity. Life Sci 2013;93:913-916.
  16. Li Y, Zhang L, Zhou J, Luo S, Huang R, Zhao C, Diao A: Nedd4 E3 ubiquitin ligase promotes cell proliferation and autophagy. Cell Prolif 2015;48:338-347.
  17. Odumosu BT, Adeniyi BA, Chandra R: First detection of OXA-10 extended-spectrum beta-lactamases and the occurrence of mexR and nfxB in clinical isolates of Pseudomonas aeruginosa from Nigeria. Chemotherapy 2016;61:87-92.
  18. Kopecka M: Microtubules and actin cytoskeleton of Cryptococcus neoformans as targets for anticancer agents to potentiate a novel approach for new antifungals. Chemotherapy 2016;61:117-121.
  19. Chou TC: Theoretical basis, experimental design, and computerized simulation of synergism and antagonism in drug combination studies. Pharmacol Rev 2006;58:621-681.
  20. Paglin S, Hollister T, Delohery T, Hackett N, McMahill M, Sphicas E, Domingo D, Yahalom J: A novel response of cancer cells to radiation involves autophagy and formation of acidic vesicles. Cancer Res 2001;61:439-444.
    External Resources
  21. Bursch W: The autophagosomal-lysosomal compartment in programmed cell death. Cell Death Differ 2001;8:569-581.
  22. Amaravadi RK, Yu D, Lum JJ, Bui T, Christophorou MA, Evan GI, Thomas-Tikhonenko A, Thompson CB: Autophagy inhibition enhances therapy-induced apoptosis in a Myc-induced model of lymphoma. J Clin Invest 2007;117:326-336.
  23. Maclean KH, Dorsey FC, Cleveland JL, Kastan MB: Targeting lysosomal degradation induces p53-dependent cell death and prevents cancer in mouse models of lymphomagenesis. J Clin Invest 2008;118:79-88.
    External Resources
  24. Lockshin RA, Zakeri Z: Programmed cell death and apoptosis: origins of the theory. Nat Rev Mol Cell Biol 2001;2:545-550.
  25. Leist M, Jaattela M: Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2001;2:589-598.
  26. Roberg K, Johansson U, Ollinger K: Lysosomal release of cathepsin D precedes relocation of cytochrome c and loss of mitochondrial transmembrane potential during apoptosis induced by oxidative stress. Free Radic Biol Med 1999;27:1228-1237.
  27. Ollinger K: Inhibition of cathepsin D prevents free-radical-induced apoptosis in rat cardiomyocytes. Arch Biochem Biophys 2000;373:346-351.
  28. Shibata M, Kanamori S, Isahara K, Ohsawa Y, Konishi A, Kametaka S, Watanabe T, Ebisu S, Ishido K, Kominami E, Uchiyama Y: Participation of cathepsins B and D in apoptosis of PC12 cells following serum deprivation. Biochem Biophys Res Commun 1998;251:199-203.
  29. Roberg K: Relocalization of cathepsin D and cytochrome c early in apoptosis revealed by immunoelectron microscopy. Lab Invest 2001;81:149-158.
  30. Vezmar M, Georges E: Reversal of MRP-mediated doxorubicin resistance with quinoline-based drugs. Biochem Pharmacol 2000;59:1245-1252.
  31. Larsen AK, Escargueil AE, Skladanowski A: Resistance mechanisms associated with altered intracellular distribution of anticancer agents. Pharmacol Ther 2000;85:217-229.
  32. Raghunand N, Martinez-Zaguilan R, Wright SH, Gillies RJ: pH and drug resistance. II. Turnover of acidic vesicles and resistance to weakly basic chemotherapeutic drugs. Biochem Pharmacol 1999;57:1047-1058.
  33. Dubowchik GM, Padilla L, Edinger K, Firestone RA: Reversal of doxorubicin resistance and catalytic neutralization of lysosomes by a lipophilic imidazole. Biochim Biophys Acta 1994;1191:103-108.

Article / Publication Details

First-Page Preview
Abstract of Anticancer Section / Original Paper

Received: May 09, 2016
Accepted: July 29, 2016
Published online: October 21, 2016
Issue release date: February 2017

Number of Print Pages: 9
Number of Figures: 5
Number of Tables: 0

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: https://www.karger.com/CHE


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