Effect of lithocholic acid on biologically active α,β-unsaturated aldehydes induced by H2O2 in glioma mitochondria for use in glioma treatment

Wang,Dan; Bie,Li; Su,Yanbin; Xu,Haoran; Zhang,Fengrong; Su,Yanwen; Zhang,Bo

doi:10.3892/ijmm.2018.3530

Effect of lithocholic acid on biologically active α,β-unsaturated aldehydes induced by H2O2 in glioma mitochondria for use in glioma treatment

Authors:
- Dan Wang
- Li Bie
- Yanbin Su
- Haoran Xu
- Fengrong Zhang
- Yanwen Su
- Bo Zhang
View Affiliations

Affiliations: Department of Ophthalmology, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Neurosurgery, First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Key Laboratory for Molecular Enzymology and Engineering, Jilin University, Changchun, Jilin 130021, P.R. China, Jilin Institute for Food and Drug Control, Changchun, Jilin 130033, P.R. China, College of Chemical and Pharmaceutical Engineering, Jilin Institute of Chemical Technology, Changchun, Jilin 132022, P.R. China
Published online on: March 2, 2018 https://doi.org/10.3892/ijmm.2018.3530
Pages: 3195-3202
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Lithocholic acid (LCA) is known to kill glioma cells while sparing normal neuronal cells. However, the anti-glioma mechanism of LCA is unclear at present. Although malondialdehyde (MDA) is not specific to detect tumors, biologically active α,β-unsaturated aldehydes can be used to detect the outcome of gliomas, especially the mitochondria, as a research tool. The purpose of this research was to determine the optimum conditions for a lipid peroxidation model, according to changes in the aldehydes formed from the reaction between 2-thiobarbituric acid and biologically active α,β-unsaturated aldehydes. Experimental methods and procedures were successfully established for a model of lipid peroxidation induced by H2O2 in glioma mitochondria for glioma treatment and optimum conditions for LCA treatment were determined. The optimal conditions for the model were a glioma mitochondrial concentration of 1.5 mg/ml, H2O2 concentration of 0.3 mg/ml, duration of action of 30 min, and addition of 4.0 ml of 46 mM thiobarbituric acid. The effect of LCA, as determined by changes in the UV peaks at 450, 495, and 532 nm, was optimal at a concentration of 100 µM, a duration of action of 15 min, and in an acidic microenvironment. The study concluded that a suitable concentration of LCA has anti-glioma effects as determined by the effect on changes in the UV peaks at 450, 495 and 532 nm and the mitochondrial model developed should be conducive to further in-depth research.

View Figures

View References

1	Goldberg AA, Beach A, Davies GF, Harkness TA, Leblanc A and Titorenko VI: Lithocholic bile acid selectively kills neuroblastoma cells, while sparing normal neuronal cells. Oncotarget. 2:761–782. 2011. View Article : Google Scholar : PubMed/NCBI
2	Tait SW and Green DR: Mitochondria and cell death: Outer membrane permeabilization and beyond. Nat Rev Mol Cell Biol. 11:621–632. 2010. View Article : Google Scholar : PubMed/NCBI
3	Jourdain A and Martinou JC: Mitochondrial outer-membrane permeabilization and remodelling in apoptosis. Int J Biochem Cell Biol. 41:1884–1889. 2009. View Article : Google Scholar : PubMed/NCBI
4	Parsons MJ and Green DR: Mitochondria in cell death. Essays Biochem. 47:99–114. 2010. View Article : Google Scholar : PubMed/NCBI
5	Miwa S and Brand MD: Mitochondrial matrix reactive oxygen species production is very sensitive to mild uncoupling. Biochem Soc Trans. 31:1300–1301. 2003. View Article : Google Scholar : PubMed/NCBI
6	Parker N, Vidal-Puig A and Brand MD: Stimulation of mitochondrial proton conductance by hydroxynonenal requires a high membrane potential. Biosci Rep. 28:83–88. 2008. View Article : Google Scholar : PubMed/NCBI
7	Papa S and Skulachev V: Reactive oxygen species, mitochondria, apoptosis and aging. Detection of Mitochondrial Diseases. Gellerich FN and Zierz S: Springer; pp. 305–319. 1997, View Article : Google Scholar
8	Brand MD: Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol. 35:811–820. 2000. View Article : Google Scholar : PubMed/NCBI
9	Esterbauer H, Schaur RJ and Zollner H: Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med. 11:81–128. 1991. View Article : Google Scholar : PubMed/NCBI
10	Lee YS and Wurster RD: Potentiation of anti-proliferative effect of nitroprusside by ascorbate in human brain tumor cells. Cancer Lett. 78:19–23. 1994. View Article : Google Scholar : PubMed/NCBI
11	Halliwell B and Chirico S: Lipid peroxidation: Its mechanism, measurement, and significance. Am J Clin Nutr. 57(Suppl 5): 715S–725S. 1993. View Article : Google Scholar : PubMed/NCBI
12	Draper HH and Hadley M: Malondialdehyde determination as index of lipid peroxidation. Methods Enzymol. 186:421–431. 1990. View Article : Google Scholar : PubMed/NCBI
13	Benedetti A, Comporti M and Esterbauer H: Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochim Biophys Acta. 620:281–296. 1980. View Article : Google Scholar : PubMed/NCBI
14	Witz G, Rao GS and Goldstein BD: Short-term toxicity of trans, trans-muconaldehyde. Toxicol Appl Pharmacol. 80:511–516. 1985. View Article : Google Scholar : PubMed/NCBI
15	Patton S and ParkKurtz GW: A note on the thiobarbituric acid test for milk lipid oxidation. J Dairy Sci. 38:9011955. View Article : Google Scholar
16	Esterbauer H, Cheeseman KH, Dianzani MU, Poli G and Slater TF: Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2⁺ in rat liver microsomes. Biochem J. 208:129–140. 1982. View Article : Google Scholar : PubMed/NCBI
17	Sinnhuber RO and Yu TC and Yu TC: Characterization of the red pigment formed in the 2-thiobarbituric acid determination of oxidative rancidity. J Food Sci. 23:626–634. 1958. View Article : Google Scholar
18	Witz G, Lawrie NJ, Zaccaria A, Ferran HE Jr and Goldstein BD: The reaction of 2-thiobarbituric acid with biologically active alpha, beta-unsaturated aldehydes. J Free Radic Biol Med. 2:33–39. 1986. View Article : Google Scholar
19	Inci S, Özcan OE and Kilinç K: Time-level relationship for lipid peroxidation and the protective effect of α-tocopherol in experimental mild and severe brain injury. Neurosurgery. 43:330–335; discussion 335-336. 1998. View Article : Google Scholar
20	Nulton-Persson AC and Szweda LI: Modulation of mitochondrial function by hydrogen peroxide. J Biol Chem. 276:23357–23361. 2001. View Article : Google Scholar : PubMed/NCBI
21	Lowry OH, Rosebrough NJ, Farr AL and Randall RJ: Protein measurement with the Folin phenol reagent. J Biol Chem. 193:265–275. 1951.PubMed/NCBI
22	Ottino P and Duncan JR: Effect of alpha-tocopherol succinate on free radical and lipid peroxidation levels in BL6 melanoma cells. Free Radic Biol Med. 22:1145–1151. 1997. View Article : Google Scholar : PubMed/NCBI
23	Malecki EA: Manganese toxicity is associated with mitochondrial dysfunction and DNA fragmentation in rat primary striatal neurons. Brain Res Bull. 55:225–228. 2001. View Article : Google Scholar : PubMed/NCBI
24	Hartley A, Stone JM, Heron C, Cooper JM and Schapira AH: Complex I inhibitors induce dose-dependent apoptosis in PC12 cells: Relevance to Parkinson's disease. J Neurochem. 63:1987–1990. 1994. View Article : Google Scholar : PubMed/NCBI
25	Sugiyama A and Sun J: Immunochemical detection of lipid hydroperoxide-and aldehyde-modified proteins in diseases. Lipid Hydroperoxide-Derived Modification of Biomolecules. Kato Y: Springer; pp. 115–125. 2014, View Article : Google Scholar
26	Park S, You X and Imlay JA: Substantial DNA damage from submicromolar intracellular hydrogen peroxide detected in Hpx- mutants of Escherichia coli. Proc Natl Acad Sci USA. 102:9317–9322. 2005. View Article : Google Scholar : PubMed/NCBI
27	Demple B, Halbrook J and Linn S: Escherichia coli xth mutants are hypersensitive to hydrogen peroxide. J Bacteriol. 153:1079–1082. 1983.PubMed/NCBI
28	Carlsson J and Carpenter VS: The recA⁺ gene product is more important than catalase and superoxide dismutase in protecting Escherichia coli against hydrogen peroxide toxicity. J Bacteriol. 142:319–321. 1980.PubMed/NCBI
29	Imlay JA and Linn S: Bimodal pattern of killing of DNA-repair-defective or anoxically grown Escherichia coli by hydrogen peroxide. J Bacteriol. 166:519–527. 1986. View Article : Google Scholar : PubMed/NCBI
30	Imlay JA, Chin SM and Linn S: Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro. Science. 240:640–642. 1988. View Article : Google Scholar : PubMed/NCBI
31	Mello Filho AC, Hoffmann ME and Meneghini R: Cell killing and DNA damage by hydrogen peroxide are mediated by intracellular iron. Biochem J. 218:273–275. 1984. View Article : Google Scholar : PubMed/NCBI
32	Bar-Or D and Winkler JV: Copper is involved in hydrogen-peroxide-induced DNA damage. Free Radic Biol Med. 32:197–199. 2002. View Article : Google Scholar : PubMed/NCBI
33	Van Kuijk FJ, Holte LL and Dratz EA: 4-Hydroxyhexenal: A lipid peroxidation product derived from oxidized docosahexaenoic acid. Biochim Biophys Acta. 1043:116–118. 1990. View Article : Google Scholar : PubMed/NCBI
34	Petersen DR and Doorn JA: Reactions of 4-hydroxynonenal with proteins and cellular targets. Free Radic Biol Med. 37:937–945. 2004. View Article : Google Scholar : PubMed/NCBI
35	Wawra E, Zollner H, Schaur RJ, Tillian HM and Schauenstein E: The inhibitory effect of 4-hydroxy-nonenal on DNA-polymerases alpha and beta from rat liver and rapidly dividing Yoshida ascites hepatoma. Cell Biochem Funct. 4:31–36. 1986. View Article : Google Scholar : PubMed/NCBI
36	Goldkorn T, Balaban N, Matsukuma K, Chea V, Gould R, Last J, Chan C and Chavez C: EGF-Receptor phosphorylation and signaling are targeted by H₂O₂ redox stress. Am J Respir Cell Mol Biol. 19:786–798. 1998. View Article : Google Scholar : PubMed/NCBI
37	Huang RP, Peng A, Golard A, Hossain MZ, Huang R, Liu YG and Boynton AL: Hydrogen peroxide promotes transformation of rat liver non-neoplastic epithelial cells through activation of epidermal growth factor receptor. Mol Carcinog. 30:209–217. 2001. View Article : Google Scholar : PubMed/NCBI
38	Petruzzelli S, Hietanen E, Bartsch H, Camus AM, Mussi A, Angeletti CA, Saracci R and Giuntini C: Pulmonary lipid peroxidation in cigarette smokers and lung cancer patients. Chest. 98:930–935. 1990. View Article : Google Scholar : PubMed/NCBI
39	Esterbauer H and Zollner H: Methods for determination of aldehydic lipid peroxidation products. Free Radic Biol Med. 7:197–203. 1989. View Article : Google Scholar : PubMed/NCBI
40	Esterbauer H, Zollner H and Scholz N: Reaction of glutathione with conjugated carbonyls. Z Naturforsch C. 30:466–473. 1975.PubMed/NCBI
41	Poot M, Verkerk A, Koster JF, Esterbauer H and Jongkind JF: Influence of cumene hydroperoxide and 4-hydroxynonenal on the glutathione metabolism during in vitro ageing of human skin fibroblasts. Eur J Biochem. 162:287–291. 1987. View Article : Google Scholar : PubMed/NCBI
42	Dogterom P, Mulder GJ and Nagelkerke JF: Lipid peroxidation-dependent and -independent protein thiol modifications in isolated rat hepatocytes: Differential effects of vitamin E and disulfiram. Chem Biol Interact. 71:291–306. 1989. View Article : Google Scholar : PubMed/NCBI
43	Poot M, Verkerk A, Koster JF, Esterbauer H and Jongkind JF: Reversible inhibition of DNA and protein synthesis by cumene hydroperoxide and 4-hydroxy-nonenal. Mech Ageing Dev. 43:1–9. 1988. View Article : Google Scholar : PubMed/NCBI
44	Esterbauer H: Kinetics of the reaction of sulfhydryl compounds with alpha-beta-unsaturated aldehydes in aqueous system. Monatsh Chem. 101:782–810. 1970. View Article : Google Scholar
45	Witz G: Biological interactions of α,β-unsaturated aldehydes. Free Radic Biol Med. 7:333–349. 1989. View Article : Google Scholar
46	Grafström RC, Dypbukt JM, Willey JC, Sundqvist K, Edman C, Atzori L and Harris CC: Pathobiological effects of acrolein in cultured human bronchial epithelial cells. Cancer Res. 48:1717–1721. 1988.PubMed/NCBI
47	Cox R, Goorha S and Irving CC: Inhibition of DNA methylase activity by acrolein. Carcinogenesis. 9:463–465. 1988. View Article : Google Scholar : PubMed/NCBI