In Vitro evaluation of thymoquinone on apoptosis and oxidative DNA damage in high glucose condition

Ali Furkan Gümüş; Semiha Dede; Veysel Yuksek; Sedat í‡etin; Mehmet Taşpınar

doi:10.14715/cmb/2018.64.14.13

Issue

Vol. 64 No. 14: Issue 14

Issue Published : December 3, 2018

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In Vitro evaluation of thymoquinone on apoptosis and oxidative DNA damage in high glucose condition

https://doi.org/10.14715/cmb/2018.64.14.13

Ali Furkan Gümüş

Health Ministry, Van Provincial Health Directorate, Van, Turkey

Semiha Dede

Department of Biochemistry, Faculty of Veterinary Medicine, Yuzuncu Yil University, Van, Turkey

Veysel Yuksek

Ozalp Vocational High School, Yuzuncu Yil University, Van, Turkey

Sedat í‡etin

Department of Biochemistry, Faculty of Veterinary Medicine, Yuzuncu Yil University, Van, Turkey

Mehmet Taşpınar

Department of Medical Biology, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey

Corresponding Author(s) : Semiha Dede

sdede@yyu.edu.tr

Cellular and Molecular Biology, Vol. 64 No. 14: Issue 14
Article Published : November 30, 2018

Abstract

The study was planned to investigate the effects of thymoquinone (TQ), which is a compound in N. sativa, on caspase dependent apoptosis and oxidative DNA damage in high glucose treated PC12 cells. PC12 cells were treated with high glucose (G1-150 mM, G2-250 mM, G3-350 mM), TQ (20 µM), and their combinations. Oxidative DNA damage (8-OHdG (8-Oxo-2'-deoxyguanosine)), and apoptosis (caspase 3, caspase 8, caspase 9 enzymes and M30 protein) parameters were analyzed with ELISA. The 8-OHdG levels decreased in all combination groups compared to the control (pâ‰¤0.001). There was no statistically significant difference between caspase 3 and 9. Caspase 8 in TQ, G3, TQG1, TQG2 groups were higher than the control (pâ‰¤0.002). Low M30 levels were observed in TQG1 group (pâ‰¤0.002). In conclusion, it was observed that in PC12 cell line treated with the high glucose concentrations, TQ administration had a statistically significant effect on oxidative DNA damage and some apoptotic parameters (caspase 8 and M30 protein).

Keywords

Caspases DNA damage High glucose In vitro Thymoquinone.

Gümüş, A. F., Dede, S., Yuksek, V., í‡etin, S., & Taşpınar, M. (2018). In Vitro evaluation of thymoquinone on apoptosis and oxidative DNA damage in high glucose condition. Cellular and Molecular Biology, 64(14), 79–83. https://doi.org/10.14715/cmb/2018.64.14.13

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References

Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine 1995;2:137-89.
Adams JM, S Cory. The Bcl-2 protein family: arbiters of cell survival. 1998;281:1322-6.
Ameisen JS. The origin of programmed cell death. Science 1996;272:1278.
Memisogullari R, Taysi S, Bakan E, Capoglu I. Antioxidant Status and Lipid Peroxidation in Type II Diabetes Mellitus. Cell Biochem Func 2003;21:291-6.
Kasai H . Chemistry-based studies on oxidative DNA damage: formation, repair, and mutagenesis. Free Radical Biol Med 2002;33:450-6
Burits M, Bucar F. Antioxidant activity of N. sativa essential oil. Phytother Res 2000;4:323-8 .
Hosseinzadeh H, Taiari S, Nassiri-Asl M. Effect of thymoquinone, a constituent of Nigella sativa L., onischemia–reperfusion in rat skeletal muscle. Naunyn-Schmiedebergs Arch Pharmacol 2012;385:503-8.
El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, Nikami H, Takewaki T. Macrophage-derived cytokine and nitric oxide profiles in type I and type II diabetes mellitus: effect of thymoquinone. Acta Diabetol 2005;42:23–30.
Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003;26:87–98
Pari L, Sankaranarayanan C. Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin-nicotinamide induced diabetic rats. Life Sci 2009;85:830-4.
Usta A, Dede S. The effect of thymoquinone treatment on Nuclear factor kappa B (NF-kB) and DNA damage on experimental diabetic rats. Pharmacog Mag 2017;13:458-61.
Usta C, Kaplan Algın A. Kardiyovasküler hastalıklara çörekotu (Nigella sativa) ile fitoterapötik yaklaşım. Ankara Akupunktur ve Tamamlayıcı Tıp Derg 2016;4:15-21
Badr G, Mahmoud MH, Farhat K, Waly H, Al-Abdin OZ, Rabah DM. Maternal supplementation of diabetic mice with thymoquinone protects their offspring from abnormal obesity and diabetes by modulating their lipid profile and free radical production and restoring lymphocyte proliferation via PI3K/AKT signaling. Lipids Health Dis 2013;12:37.
Farah N, Benghuzzi H, Tucci M, Cason Z. The effects of isolated antioxidants from black seed on the cellular metabolism of A549 cells. Biomed Sci Instrum 2005;41:211-6.
Fouad AA, Alwadani F. Ameliorative effects of thymoquinone against eye lens changes in streptozotocin diabetic rats. Environ Toxicol Pharmacol 2015;40:960-5.
Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ. Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic Î²-cells of streptozotocin-induced diabetic rats. J Diabetes 2010;2:256-66.
Rastogi L, Feroz S, Pandey BN, Jagtap A, Mishra KP. Protection against radiation–induced oxidative damage by an ethanolic extract of Nigella sativa L. Int J Radiat Biol 2010;86:719-31.
Effenberger-Neidnicht K, Schobert R. Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. Cancer Chemother Pharmacol 2011;67:867-74.
Radad KS, Al-Shraim MM, Moustafa MF, Rausch WD. Neuroprotective role of thymoquinone against 1-methyl-4-phenylpyridinium-induced dopaminergic cell death in primary mesencephalic cell culture. Neurosciences (Riyadh) 2015;20:10-6.
Gurung RL, Lim SN, Khaw AK, Soon JF, Shenoy K, Mohamed Ali S et al. Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells. PLoS One 2011;5:e12124.
Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M et al. Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res 2007;67:7782-8.
Guida MS, Abd El-Aal A, Kafafy Y, Salama SF, Badr BM, Badr G. Thymoquinone rescues T lymphocytes from gamma irradiation-induced apoptosis and exhaustion by modulating pro-inflammatory cytokine levels and PD-1, Bax, and Bcl-2 signaling. Cell Physiol Biochem 2016;38:786-800.
Paramasivam A, Raghunandhakumar S, Priyadharsini JV, Jayaraman G. In vitro anti-neuroblastoma activity of thymoquinon against neuro-2a cells via cell-cycle arrest. Asian Pac J Cancer Prev 2015;16:8313-9.
Towhid ST, Schmidt EM, Schmid E, Münzer P, Qadri SM, Borst O, Lang F. Thymoquinone-induced platelet apoptosis. J Cell Biochem 2011;112:3112-21.
El-Najjar N, Chatila M, Moukadem H, Vuorela H, Ocker M, Gandesiri M et al. Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis 2010;15:183-95.
Erkut A, Cure MC, Kalkan Y, Balik MS, Guvercin Y, Yaprak E et al. Protective effects of thymoquinone and alpha-tocopherol on the sciatic nerve and femoral muscle due to lower limb ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci 2016;20:1192-202.
Taha MM, Sheikh BY, Salim LZ, Mohan S, Khan A, Kamalidehghan B et al. Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line. Cell Mol Biol (Noisy-le-grand) 2016;62:97-101.
Yoshimura S, Banno Y, Nakashima S. Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death inhibitory effects of Bcl-2 on ceramide formation and caspase-3 activation. J Biol Chem 1998;273:6921-7.
Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. Protective effect of Nigella sativa extract and thymoquinoneon serum/glucose deprivation-induced PC12 cells death. Cell Mol Neurobiol 2010;30:591-8
Khader M, Bresgen N, Eckl PM. In vitro toxicological properties of thymoquinone. Food Chem Toxicol 2009;47:129-33.
Roepke M, Diestel A, Bajbouj K, Walluscheck D, Schonfeld P, Roessner A et al. Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biol Ther 2007;6:160-9.
Sener U, Uygur R, Aktas C, Uygur E, Erboga M, Balkas G et al. Protective effects of thymoquinone against apoptosis and oxidative stress by arsenic in rat kidney. Ren Fail 2016;38:117-23.
Yamakawa H , Ito Y, Naganawa T, Banno Y, Nakashima S, Yoshimura S et al. Activation of caspase-9 and -3 during H2O2-induced apoptosis of PC12 cells independent of ceramide formation. Neurolog Res 2000;22:556-64.

References

Marles RJ, Farnsworth NR. Antidiabetic plants and their active constituents. Phytomedicine 1995;2:137-89.

Adams JM, S Cory. The Bcl-2 protein family: arbiters of cell survival. 1998;281:1322-6.

Ameisen JS. The origin of programmed cell death. Science 1996;272:1278.

Memisogullari R, Taysi S, Bakan E, Capoglu I. Antioxidant Status and Lipid Peroxidation in Type II Diabetes Mellitus. Cell Biochem Func 2003;21:291-6.

Kasai H . Chemistry-based studies on oxidative DNA damage: formation, repair, and mutagenesis. Free Radical Biol Med 2002;33:450-6

Burits M, Bucar F. Antioxidant activity of N. sativa essential oil. Phytother Res 2000;4:323-8 .

Hosseinzadeh H, Taiari S, Nassiri-Asl M. Effect of thymoquinone, a constituent of Nigella sativa L., onischemia–reperfusion in rat skeletal muscle. Naunyn-Schmiedebergs Arch Pharmacol 2012;385:503-8.

El-Mahmoudy A, Shimizu Y, Shiina T, Matsuyama H, Nikami H, Takewaki T. Macrophage-derived cytokine and nitric oxide profiles in type I and type II diabetes mellitus: effect of thymoquinone. Acta Diabetol 2005;42:23–30.

Badary OA, Taha RA, Gamal el-Din AM, Abdel-Wahab MH. Thymoquinone is a potent superoxide anion scavenger. Drug Chem Toxicol 2003;26:87–98

Pari L, Sankaranarayanan C. Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin-nicotinamide induced diabetic rats. Life Sci 2009;85:830-4.

Usta A, Dede S. The effect of thymoquinone treatment on Nuclear factor kappa B (NF-kB) and DNA damage on experimental diabetic rats. Pharmacog Mag 2017;13:458-61.

Usta C, Kaplan Algın A. Kardiyovasküler hastalıklara çörekotu (Nigella sativa) ile fitoterapötik yaklaşım. Ankara Akupunktur ve Tamamlayıcı Tıp Derg 2016;4:15-21

Badr G, Mahmoud MH, Farhat K, Waly H, Al-Abdin OZ, Rabah DM. Maternal supplementation of diabetic mice with thymoquinone protects their offspring from abnormal obesity and diabetes by modulating their lipid profile and free radical production and restoring lymphocyte proliferation via PI3K/AKT signaling. Lipids Health Dis 2013;12:37.

Farah N, Benghuzzi H, Tucci M, Cason Z. The effects of isolated antioxidants from black seed on the cellular metabolism of A549 cells. Biomed Sci Instrum 2005;41:211-6.

Fouad AA, Alwadani F. Ameliorative effects of thymoquinone against eye lens changes in streptozotocin diabetic rats. Environ Toxicol Pharmacol 2015;40:960-5.

Abdelmeguid NE, Fakhoury R, Kamal SM, Al Wafai RJ. Effects of Nigella sativa and thymoquinone on biochemical and subcellular changes in pancreatic Î²-cells of streptozotocin-induced diabetic rats. J Diabetes 2010;2:256-66.

Rastogi L, Feroz S, Pandey BN, Jagtap A, Mishra KP. Protection against radiation–induced oxidative damage by an ethanolic extract of Nigella sativa L. Int J Radiat Biol 2010;86:719-31.

Effenberger-Neidnicht K, Schobert R. Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. Cancer Chemother Pharmacol 2011;67:867-74.

Radad KS, Al-Shraim MM, Moustafa MF, Rausch WD. Neuroprotective role of thymoquinone against 1-methyl-4-phenylpyridinium-induced dopaminergic cell death in primary mesencephalic cell culture. Neurosciences (Riyadh) 2015;20:10-6.

Gurung RL, Lim SN, Khaw AK, Soon JF, Shenoy K, Mohamed Ali S et al. Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells. PLoS One 2011;5:e12124.

Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M et al. Androgen receptor and E2F-1 targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res 2007;67:7782-8.

Guida MS, Abd El-Aal A, Kafafy Y, Salama SF, Badr BM, Badr G. Thymoquinone rescues T lymphocytes from gamma irradiation-induced apoptosis and exhaustion by modulating pro-inflammatory cytokine levels and PD-1, Bax, and Bcl-2 signaling. Cell Physiol Biochem 2016;38:786-800.

Paramasivam A, Raghunandhakumar S, Priyadharsini JV, Jayaraman G. In vitro anti-neuroblastoma activity of thymoquinon against neuro-2a cells via cell-cycle arrest. Asian Pac J Cancer Prev 2015;16:8313-9.

Towhid ST, Schmidt EM, Schmid E, Münzer P, Qadri SM, Borst O, Lang F. Thymoquinone-induced platelet apoptosis. J Cell Biochem 2011;112:3112-21.

El-Najjar N, Chatila M, Moukadem H, Vuorela H, Ocker M, Gandesiri M et al. Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis 2010;15:183-95.

Erkut A, Cure MC, Kalkan Y, Balik MS, Guvercin Y, Yaprak E et al. Protective effects of thymoquinone and alpha-tocopherol on the sciatic nerve and femoral muscle due to lower limb ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci 2016;20:1192-202.

Taha MM, Sheikh BY, Salim LZ, Mohan S, Khan A, Kamalidehghan B et al. Thymoquinone induces apoptosis and increase ROS in ovarian cancer cell line. Cell Mol Biol (Noisy-le-grand) 2016;62:97-101.

Yoshimura S, Banno Y, Nakashima S. Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death inhibitory effects of Bcl-2 on ceramide formation and caspase-3 activation. J Biol Chem 1998;273:6921-7.

Mousavi SH, Tayarani-Najaran Z, Asghari M, Sadeghnia HR. Protective effect of Nigella sativa extract and thymoquinoneon serum/glucose deprivation-induced PC12 cells death. Cell Mol Neurobiol 2010;30:591-8

Khader M, Bresgen N, Eckl PM. In vitro toxicological properties of thymoquinone. Food Chem Toxicol 2009;47:129-33.

Roepke M, Diestel A, Bajbouj K, Walluscheck D, Schonfeld P, Roessner A et al. Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biol Ther 2007;6:160-9.

Sener U, Uygur R, Aktas C, Uygur E, Erboga M, Balkas G et al. Protective effects of thymoquinone against apoptosis and oxidative stress by arsenic in rat kidney. Ren Fail 2016;38:117-23.

Yamakawa H , Ito Y, Naganawa T, Banno Y, Nakashima S, Yoshimura S et al. Activation of caspase-9 and -3 during H2O2-induced apoptosis of PC12 cells independent of ceramide formation. Neurolog Res 2000;22:556-64.

Author biographies is not available.