Pyrroloquinoline quinone induces chondrosarcoma cell apoptosis by increasing intracellular reactive oxygen species

Wen,Linchun; Lu,Xiyan; Wang,Rui; Jin,Xiaowei; Hu,Liqiang; You,Chuanwen

doi:10.3892/mmr.2018.8745

Pyrroloquinoline quinone induces chondrosarcoma cell apoptosis by increasing intracellular reactive oxygen species

Authors:
- Linchun Wen
- Xiyan Lu
- Rui Wang
- Xiaowei Jin
- Liqiang Hu
- Chuanwen You
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Affiliations: Department of Oncology, Suqian People's Hospital of Nanjing Drum Tower Hospital Group, Suqian, Jiangsu 223800, P.R. China, Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China
Published online on: March 14, 2018 https://doi.org/10.3892/mmr.2018.8745
Pages: 7184-7190
Copyright: © Wen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pyrroloquinoline quinone (PQQ) has been reported to contribute to cancer cell apoptosis and death; however, little is known of its underlying mechanisms. The present study was designed to investigate the role of PQQ in chondrosarcoma cell apoptosis and the underlying mechanism. A cell cytotoxicity assay was used to detect cell death; flow cytometry analysis was also performed to determine cell apoptosis and intracellular reactive oxygen species (ROS). Biochemical methods were employed to detect the activity and the expression of superoxide dismutase (SOD)1, SOD2 and glutathione. The present study also examined the effect on tumorigenesis in vivo. The results demonstrated that the apoptosis of SW1353 cells induced by PQQ increased in a concentration‑ and time‑dependent manner, which may be attributable to the accumulation of intracellular ROS. In the in vivo experiments, PQQ inhibited proliferation and promoted apoptosis, increased ROS levels and caused DNA damage in transplanted cells. Taken together, the findings of the present study confirmed that PQQ induced apoptosis in human chondrosarcoma SW1353 cells and transplanted cells, by increasing intracellular ROS and reducing the ability of scavenging oxygen free radicals.

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1	Bauer HC, Brosjö O, Kreicbergs A and Lindholm J: Low risk of recurrence of enchondroma and low-grade chondrosarcoma in extremities. 80 patients followed for 2–25 years. Acta Orthop Scand. 66:283–288. 1995. View Article : Google Scholar : PubMed/NCBI
2	Eriksson AI, Schiller A and Mankin HJ: The management of chondrosarcoma of bone. Clin Orthop Relat Res. 44–66. 1980.PubMed/NCBI
3	Bovée JV, Cleton-Jansen AM, Taminiau AH and Hogendoorn PC: Emerging pathways in the development of chondrosarcoma of bone and implications for targeted treatment. Lancet Oncol. 6:599–607. 2005. View Article : Google Scholar : PubMed/NCBI
4	Bao X, Ren T, Huang Y, Wang S, Zhang F, Liu K, Zheng B and Guo W: Induction of the mesenchymal to epithelial transition by demethylation-activated microRNA-125b is involved in the anti-migration/invasion effects of arsenic trioxide on human chondrosarcoma. J Exp Clin Cancer Res. 35:1292016. View Article : Google Scholar : PubMed/NCBI
5	McIntire WS: Newly discovered redox cofactors: Possible nutritional, medical, and pharmacological relevance to higher animals. Annu Rev Nutr. 18:145–177. 1998. View Article : Google Scholar : PubMed/NCBI
6	Misra HS, Khairnar NP, Barik A, Indira Priyadarsini K, Mohan H and Apte SK: Pyrroloquinoline-quinone: A reactive oxygen species scavenger in bacteria. FEBS Lett. 578:26–30. 2004. View Article : Google Scholar : PubMed/NCBI
7	He K, Nukada H, Urakami T and Murphy MP: Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): Implications for its function in biological systems. Biochem Pharmacol. 65:67–74. 2003. View Article : Google Scholar : PubMed/NCBI
8	Smidt CR, Steinberg FM and Rucker RB: Physiologic importance of pyrroloquinoline quinone. Proc Soc Exp Biol Med. 197:pp. 19–26. 1991; View Article : Google Scholar : PubMed/NCBI
9	Bishop A, Gallop PM and Karnovsky ML: Pyrroloquinoline quinone: A novel vitamin? Nutr Rev. 56:287–293. 1998. View Article : Google Scholar : PubMed/NCBI
10	Shankar BS, Pandey R, Amin P, Misra HS and Sainis KB: Role of glutathione in augmenting the anticancer activity of pyrroloquinoline quinone (PQQ). Redox Rep. 15:146–154. 2010. View Article : Google Scholar : PubMed/NCBI
11	Min Z, Wang L, Jin J, Wang X, Zhu B, Chen H and Cheng Y: Pyrroloquinoline quinone induces cancer cell apoptosis via mitochondrial-dependent pathway and down-regulating cellular Bcl-2 protein expression. J Cancer. 5:609–624. 2014. View Article : Google Scholar : PubMed/NCBI
12	Pizzimenti S, Toaldo C, Pettazzoni P, Dianzani MU and Barrera G: Thetwo-faced effects of reactive oxygen species and the lipid peroxidation product4-hydroxynonenal in the hallmarks of cancer. Cancers (Basel). 2:338–363. 2010. View Article : Google Scholar : PubMed/NCBI
13	Tripathi DN, Chowdhury R, Trudel LJ, Tee AR, Slack RS, Walker CL and Wogan GN: Reactive nitrogen species regulate autophagy through ATM-AMPK-TSC2 mediated suppression of mTORC1. Proc Natl Acad Sci USA. 110:pp. E2950–E2957. 2013; View Article : Google Scholar : PubMed/NCBI
14	Finkel T and Holbrook NJ: Oxidants, oxidative stress and the biology of ageing. Nature. 408:239–247. 2000. View Article : Google Scholar : PubMed/NCBI
15	Martindale JL and Holbrook NJ: Cellular response to oxidative stress: Signalling for suicide and survival. J Cell Physiol. 192:1–15. 2002. View Article : Google Scholar : PubMed/NCBI
16	Fang J, Nakamura H and Iyer AK: Regulation of replicative potential of cells. J Drug Target. 15:475–486. 2007. View Article : Google Scholar : PubMed/NCBI
17	Baliga R, Zhang Z, Baliga M, Ueda N and Shah SV: In vitro and in vivo evidence suggesting a role for iron in cisplatin-induced nephrotoxicity. Kidney Int. 53:394–401. 1998. View Article : Google Scholar : PubMed/NCBI
18	Xie X, Zhao Y, Ma CY, Xu XM, Zhang YQ, Wang CG, Jin J, Shen X, Gao JL, Li N, et al: Dimethyl fumarate induces necroptosis in colon cancer cells through GSH depletion/ROS increase/MAPKs activation pathway. Br J Pharmacol. 172:3929–3943. 2015. View Article : Google Scholar : PubMed/NCBI
19	Wang X, Bao Y, Dong Z, Chen Q, Guo H, Ziang C and Shao J: WP1130 attenuates cisplatin resistance by decreasing P53 expression in non-small cell lung carcinomas. Oncotarget. 8:49033–49043. 2017.PubMed/NCBI
20	Salisbury SA, Forrest HS, Cruse WB and Kennard O: A novel coenzyme from bacterial primary alcohol dehydrogenases. Nature. 280:843–844. 1979. View Article : Google Scholar : PubMed/NCBI
21	Killgore J, Smidt C, Duich L, Romero-Chapman N, Tinker D, Reiser K, Melko M, Hyde D and Rucker RB: Nutritional importance of pyrroloquinoline quinone. Science. 245:850–852. 1989. View Article : Google Scholar : PubMed/NCBI
22	Steinberg FM, Gershwin ME and Rucker RB: Dietary pyrroloquinoline quinone: Growth and immune response in BALB/c mice. J Nutr. 124:744–753. 1994. View Article : Google Scholar : PubMed/NCBI
23	Tao R, Karliner JS, Simonis U, Zheng J, Zhang J, Honbo N and Alano CC: Pyrroloquinoline quinone preserves mitochondrial function and prevents oxidative injury in adult rat cardiac myocytes. Biochem Biophys Res Commun. 363:257–262. 2007. View Article : Google Scholar : PubMed/NCBI
24	Hara H, Hiramatsu H and Adachi T: Pyrroloquinoline quinone is a potentneuroprotective nutrient against 6-hydroxydopamine-induced neurotoxicity. Neurochem Res. 32:489–495. 2007. View Article : Google Scholar : PubMed/NCBI
25	Xiong XH, Zhao Y, Ge X, Yuan SJ, Wang JH, Zhi JJ, Yang YX, Du BH, Guo WJ, Wang SS, et al: Production and radioprotective effects of pyrroloquinoline quinone. Int J Mol Sci. 12:8913–8923. 2011. View Article : Google Scholar : PubMed/NCBI
26	Sato K and Toriyama M: Effect of pyrroloquinoline quinone (PQQ) on melanogenic protein expression in murine B16 melanoma. J Dermatol Sci. 53:140–145. 2009. View Article : Google Scholar : PubMed/NCBI
27	Fadeel B and Orrenius S: Apoptosis: A basic biological phenomenon with wide-ranging implications in human disease. J Intern Med. 258:479–517. 2005. View Article : Google Scholar : PubMed/NCBI
28	Clarke PG: Developmental cell death: Morphological diversity and multiple mechanisms. Anat Embryol (Berl). 181:195–213. 1990. View Article : Google Scholar : PubMed/NCBI
29	Tibodeau JD, Benson LM, Isham CR, Owen WG and Bible KC: The Anticanceragent chaetocin is a competitive substrate and inhibitor ofthioredoxin reductase. Antioxid Redox Signal. 11:1097–1106. 2009. View Article : Google Scholar : PubMed/NCBI
30	Madan E, Prasad S, Roy P, George J and Shukla Y: Regulation of apoptosis by resveratrol through JAK/STAT and mitochondria mediated pathway in human epidermoid carcinoma A431 cells. Biochem Biophys Res Commun. 377:1232–1237. 2008. View Article : Google Scholar : PubMed/NCBI
31	Liu Z, Huang SL, Li MM, Huang ZS, Lee KS and Gu LQ: Inhibition of thioredoxin reductase by mansonone F analogues: Implications for anticancer activity. Chem Biol Interact. 177:48–57. 2009. View Article : Google Scholar : PubMed/NCBI