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Etil Piruvatın Çeşitli Kanser Hücre Hatları Üzerindeki Sitotoksik Etkisinin İncelenmesi

Year 2021, Volume: 24 Issue: 1, 49 - 56, 28.02.2021

Elif Ayazoglu Demir , Selim Demir , İbrahim Turan

https://doi.org/10.18016/ksutarimdoga.vi.707661
Cited By: 2

Abstract

Etil piruvat (EP), endojen bir metabolit olan pirüvik asitten türetilen basit bir alifatik esterdir. Çeşitli çalışmalar EP'nin antioksidan ve anti-inflamatuar özelliklerini ortaya koymuş olmasına rağmen, EP'nin kanser hücreleri üzerindeki sitotoksik etkisi hakkında sınırlı sayıda araştırma bulunmaktadır. Bu çalışmanın amacı, EP'nin yaygın kanser türlerini temsil eden hücreler üzerindeki sitotoksik etkilerini belirlemektir. Çalışmada kullanılan EP ticari olarak satın alınmış ve ara stok çözeltiler fosfat tamponu ile hazırlanmıştır. EP'nin insan melanoma (VMM917), serviks (HeLa), meme (MCF-7), akciğer (A549), karaciğer (HepG2), kolon (WiDr) kanseri ve normal fibroblast (BJ) hücreleri üzerindeki sitotoksik etkisi MTT testi kullanılarak belirlenmiştir. Sitotoksisite deneylerinde pozitif kontrol olarak sisplatin kullanılmıştır. Sonuçlar EP'nin BJ hücrelerine kıyasla VMM917 (10.1 kat) ve HeLa (3.04 kat) hücreleri üzerinde seçici sitotoksik etki gösterdiğini ortaya koymuştur. Bu çalışma, EP’nin özellikle melanoma ve serviks kanseri hücreleri üzerinde oldukça seçici bir sitotoksik etkiye sahip olduğunu ilk kez göstermektedir. Bu etkinin mekanizmasının daha kapsamlı çalışmalarla açıklanması gerekmektedir.

Keywords

Etil piruvat Hücre kültürü Kanser Sitotoksisite

References

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  • Aliyazicioglu Y, Demir S, Yaman SO, Sener SO, Demir EA, Aliyazicioglu R, Turan I 2019. Phytochemical analysis of Dorycnium pentaphyllum and its antiproliferative effect on cervix cancer cells. KSU J Agric Nat, 22(Suppl 2): 365-373.
  • Aung HH, Mehendale SR, Wang CZ, Xie JT, McEntee E 2007. Cisplatin's tumoricidal effect on human breast carcinoma MCF-7 cells was not attenuated by American ginseng. Cancer Chemother Pharmacol, 59(3): 369-374.
  • Berg KCG, Eide PW, Eilertsen IA, Johannessen B, Bruun J, Danielsen SA, Bjørnslett M, Meza-Zepeda LA, Eknæs M, Lind GE, Myklebost O, Skotheim RI, Sveen A, Lothe RA 2017. Multi-omics of 34 colorectal cancer cell lines-a resource for biomedical studies. Mol Cancer, 16(1): 116.
  • Birkenmeier G, Hemdan NY, Kurz S, Bigl M, Pieroh P, Debebe T, Buchold M, Thieme R, Wichmann G, Dehghani F, 2016. Ethyl pyruvate combats human leukemia cells but spares normal blood cells. PLoS One, 11(8): e0161571.
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  • Casagrande N, De Paoli M, Celegato M, Borghese C, Mongiat M, Colombatti A, Aldinucci D 2013. Preclinical evaluation of a new liposomal formulation of cisplatin, lipoplatin, to treat cisplatin-resistant cervical cancer. Gynecol Oncol, 131: 744-752.
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  • Kilinc K, Demir S, Turan I, Mentese A, Orem A, Sonmez M, Aliyazicioglu Y 2020. Rosa canina extract has antiproliferative and proapoptotic effects on human lung and prostate cancer cells. Nutr Cancer, 72(2): 273-282.
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  • Liang X, Chavez AR, Schapiro NE, Loughran P, Thorne SH, Amoscato AA, Zeh HJ, Beer-Stolz D, Lotze MT, de Vera ME 2009. Ethyl pyruvate administration inhibits hepatic tumor growth. J Leukoc Biol, 86(3): 599-607.
  • Lim SC, Choi EJ, Kim CH, Duong HQ, Jeong GA, Kang HS, Han SI 2007. Ethyl pyruvate induces necrosis-to-apoptosis switch and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells. Int J Mol Med, 20(2): 187-192.
  • Liu S, Gao G, Yan D, Chen X, Yao X, Guo S, Li G, Zhao Y 2017. Effects of miR-145-5p through NRAS on the cell proliferation, apoptosis, migration, and invasion in melanoma by inhibiting MAPK and PI3K/AKT pathways. Cancer Med, 6(4): 819-833.
  • Liu Q, Huo Y, Zheng H, Zhao J, Jia L, Wang P 2019. Ethyl pyruvate suppresses the growth, invasion and migration and induces the apoptosis of non-small cell lung cancer cells via the HMGB1/RAGE axis and the NF-κB/STAT3 pathway. Oncol Rep, 42(2): 817-825.
  • Makovec T 2019. Cisplatin and beyond: Molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol, 53(2): 148-158.
  • Mansouri-Torshizi H, Rezaei E, Kamranfar F, Majd MH 2016. Investigating the apoptosis ability of ethylenediamine 8-hydroxyquinolinato palladium (II) complex. Adv Pharm Bull, 6(3): 449-453.
  • Michel M, Hollenbach M, Pohl S, Ripoll C, Zipprich A 2019. Inhibition of glyoxalase-1 leads to reduced proliferation, migration and colony formation, and enhanced susceptibility to sorafenib in hepatocellular carcinoma. Front Oncol, 9: 785.
  • Misir S, Aliyazicioglu Y, Demir S, Turan I, Hepokur C 2020. Effect of Turkish propolis on miRNA expression, cell cycle, and apoptosis in human breast cancer (MCF-7) cells. Nutr Cancer, 72(1):133-145.
  • Montagner M, Sahai E 2020. In vitro models of breast cancer metastatic dormancy. Front Cell Dev Biol, 8: 37.
  • Mosmann T 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65: 55-63.
  • Narisawa-Saito M, Yoshimatsu Y, Ohno S, Yugawa T, Egawa N, Fujita M, Hirohashi S, Kiyono T 2008. An in vitro multistep carcinogenesis model for human cervical cancer. Cancer Res, 68(14): 5699-5705.
  • Park SY, Yi EY, Jung M, Lee YM, Kim YJ 2011. Ethyl pyruvate, an anti-inflammatory agent, inhibits tumor angiogenesis through inhibition of the NF-κB signaling pathway. Cancer Lett, 303: 150-154.
  • Pellegrini L, Xue J, Larson D, Pastorino S, Jube S, Forest KH, Saad-Jube ZS, Napolitano A, Pagano I, Negi VS, Bianchi ME, Morris P, Pass HI, Gaudino G, Carbone M, Yang H 2017. HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma. Oncotarget, 8(14): 22649-22661.
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  • Sappington PL, Han X, Yang R, Delude RL, Fink MP 2003. Ethyl pyruvate ameliorates intestinal epithelial barrier dysfunction in endotoxemic mice and immunostimulated Caco-2 enterocytic monolayers. J Pharmacol Exp Ther, 304(1): 464-476.
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  • Temmink OH, Hoebe EK, van der Born K, Ackland SP, Fukushima M, Peters GJ 2007. Mechanism of trifluorothymidine potentiation of oxaliplatin- induced cytotoxicity to colorectal cancer cells. Br J Cancer, 96: 231-240.
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Investigation of the Cytotoxic Effect of Ethyl Pyruvate on Various Cancer Cell Lines

Year 2021, Volume: 24 Issue: 1, 49 - 56, 28.02.2021

Elif Ayazoglu Demir , Selim Demir , İbrahim Turan

https://doi.org/10.18016/ksutarimdoga.vi.707661
Cited By: 2

Abstract

Ethyl pyruvate (EP) is a simple aliphatic ester derived from pyruvic acid which is an endogenous metabolite. Although various studies have investigated the antioxidant and anti-inflammatory properties of EP, there has been only limited research into the cytotoxic effect of EP on cancer cells. The aim of this study was to determine the cytotoxic effects of EP on cells representing common cancer types. EP was purchased commercially and intermediate stock solutions were prepared with phosphate buffer saline. The cytotoxic effect of EP on human melanoma (VMM917), cervix (HeLa), breast (MCF-7), lung (A549), liver (HepG2), colon (WiDr) cancer and normal fibroblast (BJ) cells was determined using the MTT assay. Cisplatin was used as a positive control in cytotoxicity experiments. The results showed that EP exhibits selective cytotoxic effect on VMM917 (10.1-fold) and HeLa (3.04-fold) cells compared to BJ cells. This study shows for the first time that EP has a highly selective cytotoxic effect, especially on melanoma and cervix cancer cells. The mechanism of this effect needs to be elucidated by more extensive studies.

Keywords

Cancer Cell culture Cytotoxicity Ethyl pyruvate

References

  • Adach A, Daszkiewicz M, Tyszka-Czochara M 2016. A family of complexes with N-scorpionate-type and other N-donor ligands obtained in situ from pyrazole derivative and zerovalent cobalt. Physicochemical and cytotoxicity studies. RSC Adv, 6: 44070.
  • Aliyazicioglu Y, Demir S, Yaman SO, Sener SO, Demir EA, Aliyazicioglu R, Turan I 2019. Phytochemical analysis of Dorycnium pentaphyllum and its antiproliferative effect on cervix cancer cells. KSU J Agric Nat, 22(Suppl 2): 365-373.
  • Aung HH, Mehendale SR, Wang CZ, Xie JT, McEntee E 2007. Cisplatin's tumoricidal effect on human breast carcinoma MCF-7 cells was not attenuated by American ginseng. Cancer Chemother Pharmacol, 59(3): 369-374.
  • Berg KCG, Eide PW, Eilertsen IA, Johannessen B, Bruun J, Danielsen SA, Bjørnslett M, Meza-Zepeda LA, Eknæs M, Lind GE, Myklebost O, Skotheim RI, Sveen A, Lothe RA 2017. Multi-omics of 34 colorectal cancer cell lines-a resource for biomedical studies. Mol Cancer, 16(1): 116.
  • Birkenmeier G, Hemdan NY, Kurz S, Bigl M, Pieroh P, Debebe T, Buchold M, Thieme R, Wichmann G, Dehghani F, 2016. Ethyl pyruvate combats human leukemia cells but spares normal blood cells. PLoS One, 11(8): e0161571.
  • Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A 2018. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 68(6): 394-424.
  • Casagrande N, De Paoli M, Celegato M, Borghese C, Mongiat M, Colombatti A, Aldinucci D 2013. Preclinical evaluation of a new liposomal formulation of cisplatin, lipoplatin, to treat cisplatin-resistant cervical cancer. Gynecol Oncol, 131: 744-752.
  • Cheng P, Dai W, Wang F, Lu J, Shen M, Chen K, Li J, Zhang Y, Wang C, Yang J, Zhu R, Zhang H, Zheng Y, Guo CY, Xu L 2014. Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1-RAGE and AKT pathways. Biochem Biophys Res Commun, 443(4): 1162-1168.
  • Cohen PA, Jhingran A, Oaknin A, Denny L 2019. Cervical cancer. Lancet, 393: 169-182.
  • Col Ayvaz M, Turan I, Dural B, Demir S, Karaoglu K, Aliyazicioglu Y, Serbest K 2017. Synthesis, in vitro DNA interactions, cytotoxicities, antioxidative activities, and topoisomerase inhibition potentials of Mn(II), Co(II), Ni(II), Cu(II), and Zn(II) complexes with azo-oxime ligands. Turk J Chem, 41(5): 728-747.
  • Dasari S, Tchounwou PB 2014. Cisplatin in cancer therapy: molecular mechanisms of action. Eur J Pharmacol, 740: 364-378.
  • Demir S, Turan I, Aliyazicioglu Y 2018a. Cytotoxic effect of Rhododendron luteum leaf extract on human cancer cell lines. KSU J Agric Nat, 21(6): 950-956.
  • Demir S, Turan I, Aliyazicioglu R, Ozer Yaman S, Aliyazicioglu Y 2018b. Primula vulgaris extract induces cell cycle arrest and apoptosis in human cervix cancer cells. J Pharm Anal, 8(5): 307-311.
  • Demir S, Turan I, Aliyazicioglu Y 2019a. Antioxidant properties of Primula vulgaris flower extract and its cytotoxic effect on human cancer cell lines. KSU J Agric Nat, 22(1): 78-84.
  • Demir S, Turan I, Misir S, Aliyazicioglu Y 2019b. Selective cytotoxic effect of Dorycnium pentaphyllum extract on human breast, liver, and lung cancer cells. KSU J. Agric Nat, 22(3): 473-479.
  • Demir S, Kazaz IO, Aliyazicioglu Y, Kerimoglu G, Teoman AS, Yaman SO, Arslan A, Mentese A 2020a. Effect of ethyl pyruvate on oxidative state and endoplasmic reticulum stress in a rat model of testicular torsion. Biotech Histochem, 95(4): 317-322.
  • Demir S, Ozer Yaman S, Sener SO, Ayazoglu Demir E, Aliyazicioglu R, Ozgen U, Mentese A, Deger O, Aliyazicioglu Y 2020b. Dorycnium pentaphyllum extract has antiproliferative effect on human cervix and colon cancer cells. Nutr Cancer, 72(3): 504-512.
  • Domingues B, Lopes JM, Soares P, Pópulo H 2018. Melanoma treatment in review. ImmunoTargets and Therapy, 7: 35-49.
  • Gumus F, Eren G, Acık L, Celebi A, Ozturk F, Yılmaz S, Sagkan RI, Gur S, Ozkul A, Elmalı A, Elerman Y 2009. Synthesis, cytotoxicity, and DNA interactions of new cisplatin analogues containing substituted benzimidazole ligands. J Med Chem, 52: 1345-1357.
  • Hassanpour SH, Dehghani M 2017. Review of cancer from perspective of molecular. J Cancer Res Pract, 4: 127-129.
  • Hashiesh HM, Elkhoely AA, Eissa AA, Youns MM 2018. Rosmarinic acid enhances cisplatin cytotoxicity in HepG2 cell line and attenuates its nephrotoxicity in mice. Int J Pharm Sci Res, 9(7): 2731-2743.
  • Huang B, Lv DJ, Wang C, Shu FP, Gong ZC, Xie T, Yu YZ, Song XL, Xie JJ, Li S, Liu YM, Qi H, Zhao SC 2018. Suppressed epithelial-mesenchymal transition and cancer stem cell properties mediate the anti-cancer effects of ethyl pyruvate via regulation of the AKT/nuclear factor-κB pathway in prostate cancer cells. Oncol Lett, 16(2): 2271-2278.
  • Jin C, Song P, Pang J 2019. The CK2 inhibitor CX4945 reverses cisplatin resistance in the A549/DDP human lung adenocarcinoma cell line. Oncol Lett, 18: 3845-3856.
  • Kilinc K, Demir S, Turan I, Mentese A, Orem A, Sonmez M, Aliyazicioglu Y 2020. Rosa canina extract has antiproliferative and proapoptotic effects on human lung and prostate cancer cells. Nutr Cancer, 72(2): 273-282.
  • Li QQ, Lu XF, Jia CQ, Liang XY, Jia JY, Yan KQ, Cheng BQ 2012a. Ethyl pyruvate inhibits pancreatic tumor growth in mice. Pancreatic Dis Ther, 2: 2.
  • Li ML, Wang XF, Tan ZJ, Dong P, Gu J, Lu JH, Wu XS, Zhang L, Ding QC, Wu WG, Rao LH, Mu JS, Yang JH, Weng H, Ding Q, Zhang WJ, Chen L, Liu YB 2012b. Ethyl pyruvate administration suppresses growth and invasion of gallbladder cancer cells via downregulation of HMGBl-RAGE axis. Int J Pharmacol, 25(4): 955-965.
  • Liang X, Chavez AR, Schapiro NE, Loughran P, Thorne SH, Amoscato AA, Zeh HJ, Beer-Stolz D, Lotze MT, de Vera ME 2009. Ethyl pyruvate administration inhibits hepatic tumor growth. J Leukoc Biol, 86(3): 599-607.
  • Lim SC, Choi EJ, Kim CH, Duong HQ, Jeong GA, Kang HS, Han SI 2007. Ethyl pyruvate induces necrosis-to-apoptosis switch and inhibits high mobility group box protein 1 release in A549 lung adenocarcinoma cells. Int J Mol Med, 20(2): 187-192.
  • Liu S, Gao G, Yan D, Chen X, Yao X, Guo S, Li G, Zhao Y 2017. Effects of miR-145-5p through NRAS on the cell proliferation, apoptosis, migration, and invasion in melanoma by inhibiting MAPK and PI3K/AKT pathways. Cancer Med, 6(4): 819-833.
  • Liu Q, Huo Y, Zheng H, Zhao J, Jia L, Wang P 2019. Ethyl pyruvate suppresses the growth, invasion and migration and induces the apoptosis of non-small cell lung cancer cells via the HMGB1/RAGE axis and the NF-κB/STAT3 pathway. Oncol Rep, 42(2): 817-825.
  • Makovec T 2019. Cisplatin and beyond: Molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol, 53(2): 148-158.
  • Mansouri-Torshizi H, Rezaei E, Kamranfar F, Majd MH 2016. Investigating the apoptosis ability of ethylenediamine 8-hydroxyquinolinato palladium (II) complex. Adv Pharm Bull, 6(3): 449-453.
  • Michel M, Hollenbach M, Pohl S, Ripoll C, Zipprich A 2019. Inhibition of glyoxalase-1 leads to reduced proliferation, migration and colony formation, and enhanced susceptibility to sorafenib in hepatocellular carcinoma. Front Oncol, 9: 785.
  • Misir S, Aliyazicioglu Y, Demir S, Turan I, Hepokur C 2020. Effect of Turkish propolis on miRNA expression, cell cycle, and apoptosis in human breast cancer (MCF-7) cells. Nutr Cancer, 72(1):133-145.
  • Montagner M, Sahai E 2020. In vitro models of breast cancer metastatic dormancy. Front Cell Dev Biol, 8: 37.
  • Mosmann T 1983. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods, 65: 55-63.
  • Narisawa-Saito M, Yoshimatsu Y, Ohno S, Yugawa T, Egawa N, Fujita M, Hirohashi S, Kiyono T 2008. An in vitro multistep carcinogenesis model for human cervical cancer. Cancer Res, 68(14): 5699-5705.
  • Park SY, Yi EY, Jung M, Lee YM, Kim YJ 2011. Ethyl pyruvate, an anti-inflammatory agent, inhibits tumor angiogenesis through inhibition of the NF-κB signaling pathway. Cancer Lett, 303: 150-154.
  • Pellegrini L, Xue J, Larson D, Pastorino S, Jube S, Forest KH, Saad-Jube ZS, Napolitano A, Pagano I, Negi VS, Bianchi ME, Morris P, Pass HI, Gaudino G, Carbone M, Yang H 2017. HMGB1 targeting by ethyl pyruvate suppresses malignant phenotype of human mesothelioma. Oncotarget, 8(14): 22649-22661.
  • Sakinah SAS, Handayani ST, Hawariah LPA 2007. Zerumbone induced apoptosis in liver cancer cells via modulation of Bax/Bcl-2 ratio. Cancer Cell Int, 7: 4.
  • Sappington PL, Han X, Yang R, Delude RL, Fink MP 2003. Ethyl pyruvate ameliorates intestinal epithelial barrier dysfunction in endotoxemic mice and immunostimulated Caco-2 enterocytic monolayers. J Pharmacol Exp Ther, 304(1): 464-476.
  • Sever R, Brugge JS 2015. Signal transduction in cancer. Cold Spring Harb Perspect Med, 5(4): a006098.
  • Singh TD, Meitei HT, Sharma AL, Robinson A, Singh LS, Singh TR 2015. Anticancer properties and enhancement of therapeutic potential of cisplatin by leaf extract of Zanthoxylum armatum DC. Biol Res, 48(1): 46.
  • Temmink OH, Hoebe EK, van der Born K, Ackland SP, Fukushima M, Peters GJ 2007. Mechanism of trifluorothymidine potentiation of oxaliplatin- induced cytotoxicity to colorectal cancer cells. Br J Cancer, 96: 231-240.
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There are 57 citations in total.

Details

Primary Language English
Subjects Structural Biology
Journal Section RESEARCH ARTICLE
Authors

Elif Ayazoglu Demir 0000-0001-9027-7633

Selim Demir 0000-0002-1863-6280

İbrahim Turan 0000-0003-3400-5494

Publication Date February 28, 2021
Submission Date March 23, 2020
Acceptance Date June 1, 2020
Published in Issue Year 2021 Volume: 24 Issue: 1

Cite

APA Ayazoglu Demir, E., Demir, S., & Turan, İ. (2021). Investigation of the Cytotoxic Effect of Ethyl Pyruvate on Various Cancer Cell Lines. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 24(1), 49-56. https://doi.org/10.18016/ksutarimdoga.vi.707661

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