Cisplatin impact on Kasumi-1 leukemia cell line: gene expression and DNA damage
Yıl 2025,
Cilt: 18 Sayı: 1, 6 - 6
Yavuz Dodurga
,
Mücahit Seçme
,
Levent Elmas
,
Nazlı Demirkıran
,
Sevda Sağ
,
Ulviye Adamcı
,
Zeliha Akdağ
Öz
Purpose: Leukemia is a type of cancer caused by the uncontrolled proliferation of blood cells. The purpose of this study was to investigate the effects of cisplatin (CIS), a chemotherapeutic agent used in the treatment of leukemia, on the Kasumi-1 leukemia cell line.
Materials and methods: The study measured the effect of CIS on Kasumi-1 cells by calculating IC50 values for cell viability. The mRNA expression levels of apoptosis and cell cycle-related genes were then assessed using Real-Time PCR. In addition, the effects of CIS on DNA damage were investigated using the comet assay.
Results: Significant changes in apoptosis and cell cycle-related genes were observed in CIS-treated groups. These included alterations in the mRNA levels of p53, BCL-2, CHECK 1, CDC25C, CDK 6, URG4/URGCP, GADD45A, CCND1, GADD45G, and ATM genes. Comet analysis confirmed CIS's effects on DNA damage.
Conclusion: This study aimed to better understand how CIS affects genetic mechanisms in leukemia cells and provide new insights into leukemia treatment. The findings will help us better understand the role of CIS in leukemia treatment and will serve as a valuable reference for future research.
Kaynakça
- Brown A, Kumar S, Tchounwou PB. Cisplatin-Based Chemotherapy of Human Cancers. J Cancer Sci Ther. 2019;11(4):97
- Chan WI, Huntly BJ. Leukemia stem cells in acute myeloid leukemia. Semin Oncol. 2008;35(4):326-335. doi:10.1053/j.seminoncol.2008.04.003
- Thomas D, Majeti R. Biology and relevance of human acute myeloid leukemia stem cells. Blood. 2017;129(12):1577-1585. doi:10.1182/blood-2016-10-696054
- Hernandez FYF, Khandual S, López IGR. Cytotoxic effect of Spirulina platensis extracts on human acute leukemia Kasumi-1 and chronic myelogenous leukemia K-562 cell lines. Asian Pac J Trop Biomed 2017;7:14-19. doi.org/10.1016/j.apjtb.2016.10.011
- Corrie PG. Cytotoxic chemotherapy: clinical aspects. Med. 2008;36:24-28. doi.org/10.1016/j.mpmed.2007.10.012
- Dasari S, Njiki S, Mbemi A, Yedjou CG, Tchounwou PB. Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy. Int J Mol Sci. 2022;23(3):1532. Published 2022 Jan 28. doi:10.3390/ijms23031532
- Perše M, Večerić-Haler Ž. Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges. Biomed Res Int. 2018;2018:1462802. Published 2018 Sep 12. doi:10.1155/2018/1462802
- Makovec T. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol. 2019;53(2):148-158. Published 2019 Mar 28. doi:10.2478/raon-2019-0018
- Barabas K, Milner R, Lurie D, Adin C. Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol. 2008;6(1):1-18. doi:10.1111/j.1476-5829.2007.00142.x
- Aldossary SA. Review on pharmacology of cisplatin: clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J 2019;12:7-15. doi.org/10.13005/bpj/1608
- Gundogdu G, Dodurga Y, Cetin M, Secme M, Cicek B. The cytotoxic and genotoxic effects of daidzein on MIA PaCa-2 human pancreatic carcinoma cells and HT-29 human colon cancer cells. Drug Chem Toxicol. 2020;43(6):581-587. doi:10.1080/01480545.2018.1527849
- Dodurga Y, Oymak Y, Gündüz C, et al. Leukemogenesis as a new approach to investigate the correlation between up regulated gene 4/upregulator of cell proliferation (URG4/URGCP) and signal transduction genes in leukemia. Mol Biol Rep. 2013;40(4):3043-3048. doi:10.1007/s11033-012-2378-1
- Dodurga Y, Elmas L, Seçme M. Investigation of the apoptotic and cell cycle effects of sorafenib and doxorubicin on URG4/URGCP in leukemia cells. Pam Med J 2024;17:498-508. doi.org/10.31362/patd.1476105
- Saultz JN, Garzon R. Acute Myeloid Leukemia: A Concise Review. J Clin Med. 2016;5(3):33. Published 2016 Mar 5. doi:10.3390/jcm5030033
- Winer ES, Stone RM. Novel therapy in Acute myeloid leukemia (AML): moving toward targeted approaches. Ther Adv Hematol. 2019;10:2040620719860645. Published 2019 Jul 10. doi:10.1177/2040620719860645
- Giles FJ, Keating A, Goldstone AH, Avivi I, Willman CL, Kantarjian HM. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2002;73-110. doi:10.1182/asheducation-2002.1.73
- Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Pediatr Clin North Am. 2008;55(1):21-ix. doi:10.1016/j.pcl.2007.11.003
- Makin G, Dive C. Apoptosis and cancer chemotherapy. Trends Cell Biol. 2001;11(11):S22-S26. doi:10.1016/s0962-8924(01)02124-9
- Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int J Mol Sci. 2020;21(9):3233. Published 2020 May 2. doi:10.3390/ijms21093233
- Ramadori G, Cameron S. Effects of systemic chemotherapy on the liver. Ann Hepatol. 2010;9(2):133-143
- DeBacker JR, Harrison RT, Bielefeld EC. Long-Term Synergistic Interaction of Cisplatin- and Noise-Induced Hearing Losses. Ear Hear. 2017;38(3):282-291. doi:10.1097/AUD.0000000000000391
- Cohen SM, Lippard SJ. Cisplatin: from DNA damage to cancer chemotherapy. Prog Nucleic Acid Res Mol Biol. 2001;67:93-130. doi:10.1016/s0079-6603(01)67026-0
- Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30(14):1692-1698. doi:10.1200/JCO.2011.40.4905
- Breglio AM, Rusheen AE, Shide ED, et al. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun. 2017;8(1):1654. Published 2017 Nov 21. doi:10.1038/s41467-017-01837-1
- Zhang J, Ye ZW, Tew KD, Townsend DM. Cisplatin chemotherapy and renal function. Adv Cancer Res. 2021;152:305-327. doi:10.1016/bs.acr.2021.03.008
- Hussain Y, Islam L, Khan H, Filosa R, Aschner M, Javed S. Curcumin-cisplatin chemotherapy: A novel strategy in promoting chemotherapy efficacy and reducing side effects. Phytother Res. 2021;35(12):6514-6529. doi:10.1002/ptr.7225
- Cho HJ, Kim JK, Kim KD, et al. Upregulation of Bcl-2 is associated with cisplatin-resistance via inhibition of Bax translocation in human bladder cancer cells. Cancer Lett. 2006;237(1):56-66. doi:10.1016/j.canlet.2005.05.039
- Nishioka T, Luo LY, Shen L, et al. Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability. Br J Cancer. 2014;110(7):1785-1792. doi:10.1038/bjc.2014.78
- Yuan Y, Wang H, Wu Y, et al. P53 Contributes to Cisplatin Induced Renal Oxidative Damage via Regulating P66shc and MnSOD. Cell Physiol Biochem. 2015;37(4):1240-1256. doi:10.1159/000430247
- Qu K, Lin T, Wei J, et al. Cisplatin induces cell cycle arrest and senescence via upregulating P53 and P21 expression in HepG2 cells. Nan Fang Yi Ke Da Xue Xue Bao. 2013;33(9):1253-1259
- Yousef MI, Hussien HM. Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng. Food Chem Toxicol. 2015;78:17-25. doi:10.1016/j.fct.2015.01.014
- Sakai R, Morikawa Y, Kondo C, et al. Combinatorial measurement of CDKN1A/p21 and KIF20A expression for discrimination of DNA damage-induced clastogenicity. Int J Mol Sci. 2014;15(10):17256-17269. Published 2014 Sep 26. doi:10.3390/ijms151017256
- Horibe S, Matsuda A, Tanahashi T, et al. Cisplatin resistance in human lung cancer cells is linked with dysregulation of cell cycle associated proteins. Life Sci. 2015;124:31-40. doi:10.1016/j.lfs.2015.01.011
- Sarin N, Engel F, Kalayda GV, et al. Cisplatin resistance in non-small cell lung cancer cells is associated with an abrogation of cisplatin-induced G2/M cell cycle arrest. PLoS One. 2017;12(7):e0181081. Published 2017 Jul 26. doi:10.1371/journal.pone.0181081
- Yamashita N, Nakai K, Nakata T, et al. Cumulative DNA damage by repeated low-dose cisplatin injection promotes the transition of acute to chronic kidney injury in mice. Sci Rep. 2021;11(1):20920. Published 2021 Oct 22. doi:10.1038/s41598-021-00392-6
- Sharifan A, Etebari M, Zolfaghari B, Aliomrani M. Investigating the effects of bark extract and volatile oil of Pinus eldarica against cisplatin-induced genotoxicity on HUVECs cell line. Toxicol Res (Camb). 2021;10(2):223-231. Published 2021 Mar 23. doi:10.1093/toxres/tfab006
- Li J, Ma X, Xu F, Yan Y, Chen W. Babaodan overcomes cisplatin resistance in cholangiocarcinoma via inhibiting YAP1. Pharm Biol. 2024;62(1):314-325. doi:10.1080/13880209.2024.2331060
Sisplatinin Kasumi-1 Lösemisi Üzerindeki Etkisi: Gen Ekspresyonu ve DNA Hasarı
Yıl 2025,
Cilt: 18 Sayı: 1, 6 - 6
Yavuz Dodurga
,
Mücahit Seçme
,
Levent Elmas
,
Nazlı Demirkıran
,
Sevda Sağ
,
Ulviye Adamcı
,
Zeliha Akdağ
Öz
Amaç: Lösemi, kan hücrelerinin kontrolsüz çoğalması sonucu ortaya çıkan bir kanser türüdür. Bu çalışmanın amacı, lösemi tedavisinde kullanılan kemoterapötik bir ajan olan sisplatinin (CIS) Kasumi-1 lösemi hücre hattı üzerindeki etkilerini araştırmaktır.
Gereç ve yöntemler: Çalışmada, hücre canlılığı için IC50 değerleri hesaplanarak CIS'in Kasumi-1 hücreleri üzerindeki etkisi ölçülmüştür. Apoptoz ve hücre döngüsü ile ilgili genlerin mRNA ekspresyon seviyeleri daha sonra Real-Time PCR kullanılarak değerlendirilmiştir. Ayrıca, CIS'in DNA hasarı üzerindeki etkileri comet testi kullanılarak araştırılmıştır.
Bulgular: CIS ile tedavi edilen gruplarda apoptoz ve hücre döngüsü ile ilgili genlerde önemli değişiklikler gözlendi. Bunlar arasında p53, BCL-2, CHECK 1, CDC25C, CDK 6, URG4/URGCP, GADD45A, CCND1, GADD45G ve ATM genlerinin mRNA seviyelerindeki değişiklikler yer aldı. Comet analizi CIS'in DNA hasarı üzerindeki etkilerini doğrulamıştır.
Sonuç: Bu çalışma, CIS'in lösemi hücrelerindeki genetik mekanizmaları nasıl etkilediğini daha iyi anlamayı ve lösemi tedavisine yeni bakış açıları sağlamayı amaçlamıştır. Bulgular, CIS'in lösemi tedavisindeki rolünü daha iyi anlamamıza yardımcı olacak ve gelecekteki araştırmalar için değerli bir referans görevi görecektir.
Kaynakça
- Brown A, Kumar S, Tchounwou PB. Cisplatin-Based Chemotherapy of Human Cancers. J Cancer Sci Ther. 2019;11(4):97
- Chan WI, Huntly BJ. Leukemia stem cells in acute myeloid leukemia. Semin Oncol. 2008;35(4):326-335. doi:10.1053/j.seminoncol.2008.04.003
- Thomas D, Majeti R. Biology and relevance of human acute myeloid leukemia stem cells. Blood. 2017;129(12):1577-1585. doi:10.1182/blood-2016-10-696054
- Hernandez FYF, Khandual S, López IGR. Cytotoxic effect of Spirulina platensis extracts on human acute leukemia Kasumi-1 and chronic myelogenous leukemia K-562 cell lines. Asian Pac J Trop Biomed 2017;7:14-19. doi.org/10.1016/j.apjtb.2016.10.011
- Corrie PG. Cytotoxic chemotherapy: clinical aspects. Med. 2008;36:24-28. doi.org/10.1016/j.mpmed.2007.10.012
- Dasari S, Njiki S, Mbemi A, Yedjou CG, Tchounwou PB. Pharmacological Effects of Cisplatin Combination with Natural Products in Cancer Chemotherapy. Int J Mol Sci. 2022;23(3):1532. Published 2022 Jan 28. doi:10.3390/ijms23031532
- Perše M, Večerić-Haler Ž. Cisplatin-Induced Rodent Model of Kidney Injury: Characteristics and Challenges. Biomed Res Int. 2018;2018:1462802. Published 2018 Sep 12. doi:10.1155/2018/1462802
- Makovec T. Cisplatin and beyond: molecular mechanisms of action and drug resistance development in cancer chemotherapy. Radiol Oncol. 2019;53(2):148-158. Published 2019 Mar 28. doi:10.2478/raon-2019-0018
- Barabas K, Milner R, Lurie D, Adin C. Cisplatin: a review of toxicities and therapeutic applications. Vet Comp Oncol. 2008;6(1):1-18. doi:10.1111/j.1476-5829.2007.00142.x
- Aldossary SA. Review on pharmacology of cisplatin: clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J 2019;12:7-15. doi.org/10.13005/bpj/1608
- Gundogdu G, Dodurga Y, Cetin M, Secme M, Cicek B. The cytotoxic and genotoxic effects of daidzein on MIA PaCa-2 human pancreatic carcinoma cells and HT-29 human colon cancer cells. Drug Chem Toxicol. 2020;43(6):581-587. doi:10.1080/01480545.2018.1527849
- Dodurga Y, Oymak Y, Gündüz C, et al. Leukemogenesis as a new approach to investigate the correlation between up regulated gene 4/upregulator of cell proliferation (URG4/URGCP) and signal transduction genes in leukemia. Mol Biol Rep. 2013;40(4):3043-3048. doi:10.1007/s11033-012-2378-1
- Dodurga Y, Elmas L, Seçme M. Investigation of the apoptotic and cell cycle effects of sorafenib and doxorubicin on URG4/URGCP in leukemia cells. Pam Med J 2024;17:498-508. doi.org/10.31362/patd.1476105
- Saultz JN, Garzon R. Acute Myeloid Leukemia: A Concise Review. J Clin Med. 2016;5(3):33. Published 2016 Mar 5. doi:10.3390/jcm5030033
- Winer ES, Stone RM. Novel therapy in Acute myeloid leukemia (AML): moving toward targeted approaches. Ther Adv Hematol. 2019;10:2040620719860645. Published 2019 Jul 10. doi:10.1177/2040620719860645
- Giles FJ, Keating A, Goldstone AH, Avivi I, Willman CL, Kantarjian HM. Acute myeloid leukemia. Hematology Am Soc Hematol Educ Program. 2002;73-110. doi:10.1182/asheducation-2002.1.73
- Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Pediatr Clin North Am. 2008;55(1):21-ix. doi:10.1016/j.pcl.2007.11.003
- Makin G, Dive C. Apoptosis and cancer chemotherapy. Trends Cell Biol. 2001;11(11):S22-S26. doi:10.1016/s0962-8924(01)02124-9
- Bukowski K, Kciuk M, Kontek R. Mechanisms of Multidrug Resistance in Cancer Chemotherapy. Int J Mol Sci. 2020;21(9):3233. Published 2020 May 2. doi:10.3390/ijms21093233
- Ramadori G, Cameron S. Effects of systemic chemotherapy on the liver. Ann Hepatol. 2010;9(2):133-143
- DeBacker JR, Harrison RT, Bielefeld EC. Long-Term Synergistic Interaction of Cisplatin- and Noise-Induced Hearing Losses. Ear Hear. 2017;38(3):282-291. doi:10.1097/AUD.0000000000000391
- Cohen SM, Lippard SJ. Cisplatin: from DNA damage to cancer chemotherapy. Prog Nucleic Acid Res Mol Biol. 2001;67:93-130. doi:10.1016/s0079-6603(01)67026-0
- Rossi A, Di Maio M, Chiodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin Oncol. 2012;30(14):1692-1698. doi:10.1200/JCO.2011.40.4905
- Breglio AM, Rusheen AE, Shide ED, et al. Cisplatin is retained in the cochlea indefinitely following chemotherapy. Nat Commun. 2017;8(1):1654. Published 2017 Nov 21. doi:10.1038/s41467-017-01837-1
- Zhang J, Ye ZW, Tew KD, Townsend DM. Cisplatin chemotherapy and renal function. Adv Cancer Res. 2021;152:305-327. doi:10.1016/bs.acr.2021.03.008
- Hussain Y, Islam L, Khan H, Filosa R, Aschner M, Javed S. Curcumin-cisplatin chemotherapy: A novel strategy in promoting chemotherapy efficacy and reducing side effects. Phytother Res. 2021;35(12):6514-6529. doi:10.1002/ptr.7225
- Cho HJ, Kim JK, Kim KD, et al. Upregulation of Bcl-2 is associated with cisplatin-resistance via inhibition of Bax translocation in human bladder cancer cells. Cancer Lett. 2006;237(1):56-66. doi:10.1016/j.canlet.2005.05.039
- Nishioka T, Luo LY, Shen L, et al. Nicotine increases the resistance of lung cancer cells to cisplatin through enhancing Bcl-2 stability. Br J Cancer. 2014;110(7):1785-1792. doi:10.1038/bjc.2014.78
- Yuan Y, Wang H, Wu Y, et al. P53 Contributes to Cisplatin Induced Renal Oxidative Damage via Regulating P66shc and MnSOD. Cell Physiol Biochem. 2015;37(4):1240-1256. doi:10.1159/000430247
- Qu K, Lin T, Wei J, et al. Cisplatin induces cell cycle arrest and senescence via upregulating P53 and P21 expression in HepG2 cells. Nan Fang Yi Ke Da Xue Xue Bao. 2013;33(9):1253-1259
- Yousef MI, Hussien HM. Cisplatin-induced renal toxicity via tumor necrosis factor-α, interleukin 6, tumor suppressor P53, DNA damage, xanthine oxidase, histological changes, oxidative stress and nitric oxide in rats: protective effect of ginseng. Food Chem Toxicol. 2015;78:17-25. doi:10.1016/j.fct.2015.01.014
- Sakai R, Morikawa Y, Kondo C, et al. Combinatorial measurement of CDKN1A/p21 and KIF20A expression for discrimination of DNA damage-induced clastogenicity. Int J Mol Sci. 2014;15(10):17256-17269. Published 2014 Sep 26. doi:10.3390/ijms151017256
- Horibe S, Matsuda A, Tanahashi T, et al. Cisplatin resistance in human lung cancer cells is linked with dysregulation of cell cycle associated proteins. Life Sci. 2015;124:31-40. doi:10.1016/j.lfs.2015.01.011
- Sarin N, Engel F, Kalayda GV, et al. Cisplatin resistance in non-small cell lung cancer cells is associated with an abrogation of cisplatin-induced G2/M cell cycle arrest. PLoS One. 2017;12(7):e0181081. Published 2017 Jul 26. doi:10.1371/journal.pone.0181081
- Yamashita N, Nakai K, Nakata T, et al. Cumulative DNA damage by repeated low-dose cisplatin injection promotes the transition of acute to chronic kidney injury in mice. Sci Rep. 2021;11(1):20920. Published 2021 Oct 22. doi:10.1038/s41598-021-00392-6
- Sharifan A, Etebari M, Zolfaghari B, Aliomrani M. Investigating the effects of bark extract and volatile oil of Pinus eldarica against cisplatin-induced genotoxicity on HUVECs cell line. Toxicol Res (Camb). 2021;10(2):223-231. Published 2021 Mar 23. doi:10.1093/toxres/tfab006
- Li J, Ma X, Xu F, Yan Y, Chen W. Babaodan overcomes cisplatin resistance in cholangiocarcinoma via inhibiting YAP1. Pharm Biol. 2024;62(1):314-325. doi:10.1080/13880209.2024.2331060