Cytoprotective Effects of Acidosis Via Heat Shock Protein HSP27 Against the Anticancer Drug Doxorubicin

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2010 Aug 24

PMID 20730553

Citations 5

Authors

Anurag Kumar Singh

Michael P Manns

Ursula Seidler

Affiliations

Soon will be listed here.

Abstract

Drug resistance continues to be a stumbling block in achieving better cure rates in several cancers. Doxorubicin is commonly used in treatment of a wide range of cancers. The aim of this study was to look into the mechanisms of how low ambient pH may contribute to down-regulation of apoptotic pathways in a gastric tumour cell line. Low pH culture conditions were found to dramatically prolong cell survival after doxorubicin treatment, an effect that was in part reversed by co-incubation with the specific p38 mitoge-activated protein kinase (MAP kinase) inhibitor SB203580, only mildly inhibited by blockade of the multi-drug resistance 1 (MDR1) transporter, but completely abolished by siRNA-mediated knockdown of the heat shock protein 27 (HSP27). In conclusion, acidic pH causes less accumulation of cytotoxic drug in the nucleus of adeno gastric carcinoma (AGS) cells and HSP27-dependent decrease in FasR-mediated gastric epithelial tumour cell apoptosis.

Citing Articles

Proteomic Profiling and Pathway Analysis of Acid Stress-Induced Vasorelaxation of Mesenteric Arteries In Vitro.

Mohanty I, Banerjee S, Mahanty A, Mohanty S, Nayak N, Parija S Genes (Basel). 2022; 13(5).

PMID: 35627186 PMC: 9140505. DOI: 10.3390/genes13050801.

Effects of extracellular acidity on resistance to chemotherapy treatment: a systematic review.

da Silva V, Mesquita C, Nunes J, de Bem Prunes B, Rados P, Visioli F Med Oncol. 2018; 35(12):161.

PMID: 30377828 DOI: 10.1007/s12032-018-1214-4.

pH-dependent structural modulation is conserved in the human small heat shock protein HSBP1.

Clouser A, Klevit R Cell Stress Chaperones. 2017; 22(4):569-575.

PMID: 28332148 PMC: 5465033. DOI: 10.1007/s12192-017-0783-z.

Glucose-regulated protein 78 (Grp78) confers chemoresistance to tumor endothelial cells under acidic stress.

Visioli F, Wang Y, Alam G, Ning Y, Rados P, Nor J PLoS One. 2014; 9(6):e101053.

PMID: 24964091 PMC: 4071032. DOI: 10.1371/journal.pone.0101053.

SB202190-induced cell type-specific vacuole formation and defective autophagy do not depend on p38 MAP kinase inhibition.

Menon M, Kotlyarov A, Gaestel M PLoS One. 2011; 6(8):e23054.

PMID: 21853067 PMC: 3154272. DOI: 10.1371/journal.pone.0023054.

References

Gatenby R, Gawlinski E . A reaction-diffusion model of cancer invasion. Cancer Res. 1996; 56(24):5745-53. View

Kuwano M, Toh S, Uchiumi T, Takano H, Kohno K, Wada M . Multidrug resistance-associated protein subfamily transporters and drug resistance. Anticancer Drug Des. 1999; 14(2):123-31. View

Montecucco C, Rappuoli R . Living dangerously: how Helicobacter pylori survives in the human stomach. Nat Rev Mol Cell Biol. 2001; 2(6):457-66. DOI: 10.1038/35073084. View

Martinez-Zaguilan R, Lynch R, Martinez G, Gillies R . Vacuolar-type H(+)-ATPases are functionally expressed in plasma membranes of human tumor cells. Am J Physiol. 1993; 265(4 Pt 1):C1015-29. DOI: 10.1152/ajpcell.1993.265.4.C1015. View

Yaniv G, Shilkrut M, Lotan R, Berke G, Larisch S, Binah O . Hypoxia predisposes neonatal rat ventricular myocytes to apoptosis induced by activation of the Fas (CD95/Apo-1) receptor: Fas activation and apoptosis in hypoxic myocytes. Cardiovasc Res. 2002; 54(3):611-23. DOI: 10.1016/s0008-6363(02)00264-x. View

Rossmann H, Sonnentag T, Heinzmann A, Seidler B, Bachmann O, Gregor M . Differential expression and regulation of Na(+)/H(+) exchanger isoforms in rabbit parietal and mucous cells. Am J Physiol Gastrointest Liver Physiol. 2001; 281(2):G447-58. DOI: 10.1152/ajpgi.2001.281.2.G447. View

Nakamura T, Ueda Y, Juan Y, Katsuda S, Takahashi H, Koh E . Fas-mediated apoptosis in adriamycin-induced cardiomyopathy in rats: In vivo study. Circulation. 2000; 102(5):572-8. DOI: 10.1161/01.cir.102.5.572. View

Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C . Cancer statistics, 2006. CA Cancer J Clin. 2006; 56(2):106-30. DOI: 10.3322/canjclin.56.2.106. View

Rouse J, Cohen P, Trigon S, Morange M, Alonso-Llamazares A, Zamanillo D . A novel kinase cascade triggered by stress and heat shock that stimulates MAPKAP kinase-2 and phosphorylation of the small heat shock proteins. Cell. 1994; 78(6):1027-37. DOI: 10.1016/0092-8674(94)90277-1. View

10.

Miyata S, Takemura G, Kosai K, Takahashi T, Esaki M, Li L . Anti-Fas gene therapy prevents doxorubicin-induced acute cardiotoxicity through mechanisms independent of apoptosis. Am J Pathol. 2009; 176(2):687-98. PMC: 2808076. DOI: 10.2353/ajpath.2010.090222. View

11.

Lelj-Garolla B, Mauk A . Self-association and chaperone activity of Hsp27 are thermally activated. J Biol Chem. 2006; 281(12):8169-74. DOI: 10.1074/jbc.M512553200. View

12.

Bachmann O, Sonnentag T, Siegel W, Lamprecht G, Weichert A, Gregor M . Different acid secretagogues activate different Na+/H+ exchanger isoforms in rabbit parietal cells. Am J Physiol. 1998; 275(5):G1085-93. DOI: 10.1152/ajpgi.1998.275.5.G1085. View

13.

Allen A, Flemstrom G . Gastroduodenal mucus bicarbonate barrier: protection against acid and pepsin. Am J Physiol Cell Physiol. 2004; 288(1):C1-19. DOI: 10.1152/ajpcell.00102.2004. View

14.

Vaupel P, Kallinowski F, Okunieff P . Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res. 1989; 49(23):6449-65. View

15.

Shen F, Chu S, Bence A, Bailey B, Xue X, Erickson P . Quantitation of doxorubicin uptake, efflux, and modulation of multidrug resistance (MDR) in MDR human cancer cells. J Pharmacol Exp Ther. 2007; 324(1):95-102. DOI: 10.1124/jpet.107.127704. View

16.

Gottlieb R, Giesing H, Zhu J, Engler R, Babior B . Cell acidification in apoptosis: granulocyte colony-stimulating factor delays programmed cell death in neutrophils by up-regulating the vacuolar H(+)-ATPase. Proc Natl Acad Sci U S A. 1995; 92(13):5965-8. PMC: 41622. DOI: 10.1073/pnas.92.13.5965. View

17.

Havasi A, Li Z, Wang Z, Martin J, Botla V, Ruchalski K . Hsp27 inhibits Bax activation and apoptosis via a phosphatidylinositol 3-kinase-dependent mechanism. J Biol Chem. 2008; 283(18):12305-13. PMC: 2431006. DOI: 10.1074/jbc.M801291200. View

18.

Charette S, Lavoie J, Lambert H, Landry J . Inhibition of Daxx-mediated apoptosis by heat shock protein 27. Mol Cell Biol. 2000; 20(20):7602-12. PMC: 86317. DOI: 10.1128/MCB.20.20.7602-7612.2000. View

19.

Williams A, Collard T, Paraskeva C . An acidic environment leads to p53 dependent induction of apoptosis in human adenoma and carcinoma cell lines: implications for clonal selection during colorectal carcinogenesis. Oncogene. 1999; 18(21):3199-204. DOI: 10.1038/sj.onc.1202660. View

20.

McLean L, Roscoe J, Jorgensen N, Gorin F, Cala P . Malignant gliomas display altered pH regulation by NHE1 compared with nontransformed astrocytes. Am J Physiol Cell Physiol. 2001; 278(4):C676-88. DOI: 10.1152/ajpcell.2000.278.4.C676. View