Dergiler / European Journal of Biology / 2025 / Volume: 84 Issue: 2

Comparison of Catechol-Induced Expression Levels of ATM, ATR, BAX, BCL2, and CCND1 Genes Between Parental and Epirubicin-Resistant NSCLC Cells

Zeynep Demir(AKDENİZ ÜNİVERSİTESİ)0000-0003-4014-8467
Aysun Özkan(AKDENİZ ÜNİVERSİTESİ, FEN FAKÜLTESİ)0000-0002-9403-3342
Berkay Sungur(BOĞAZİÇİ ÜNİVERSİTESİ)0000-0002-5567-0146
Sayfa
—
Yayın Tarihi
2025-12-18
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⚡ TL;DR(1 Cümlede Hızlı Çıkarım)

This study proposes a promising direction for the development of safer and more effective chemotherapy drugs that spare healthy cells and potential clinical applications for catechol.

📌 3 Maddede Bu Makale

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Amaç & Hipotez:Objective: This study investigated the apoptotic effects of catechol on lung cancer by comparing gene expression levels in parental lung cancer cells (P-H1299), Epirubicin-HCl resistant lung cancer cells (R H1299), and healthy fibroblast cells (Bj).
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Temel Bulgular & Veri:To understand the apoptotic effect of catechol, caspase-3/7 activity was measured using a kit.
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Sonuç & Katkı:This study proposes a promising direction for the development of safer and more effective chemotherapy drugs that spare healthy cells and potential clinical applications for catechol.
🔬Tür:Research Article
📍Kapsam:Genişletilmiş Akademik Örneklem
⚙️Değişkenler:Apoptosis · Catechol · Drug resistance

Abstract

Objective: This study investigated the apoptotic effects of catechol on lung cancer by comparing gene expression levels in parental lung cancer cells (P-H1299), Epirubicin-HCl resistant lung cancer cells (R H1299), and healthy fibroblast cells (Bj). Materials and Methods: The cytotoxic effects of catechol on cells were determined using a Cell Titer-Blue Cell viability assay. To understand the apoptotic effect of catechol, caspase-3/7 activity was measured using a kit. RT-PCR was used to measure the mRNA expression of the ATM, ATR, BAX, BCL2, CCND1, and PCNA genes. Results: The IC₅₀ values for catechol were determined to be 58 µM for P-H1299, 90 µM for R-H1299, and 207 µM for BJ cells, indicating selective cytotoxicity towards cancerous cells. Caspase 3 activity and Bax/Bcl-2 ratio analyses revealed increased apoptosis in cancer cells, especially in drug-resistant R-H1299 cells. Gene expression analysis revealed increased ATM and ATR mRNA levels in P-H1299 cells, indicating the most DNA damage. Molecular docking studies have suggested that catechol's lower DNA binding affinity compared with known intercalating agents, such as Epirubicin and Doxorubicin, implies a mechanism of action reliant on reactive oxygen species rather than direct DNA intercalation. Efficient antioxidant mechanisms facilitate high survival rates of healthy cells. Conclusion: Results indicate that catechol cytotoxicity is mainly caused by ROS-induced DNA damage, offering a novel strategy for targeting both parental and drug-resistant lung cancer cells. This study proposes a promising direction for the development of safer and more effective chemotherapy drugs that spare healthy cells and potential clinical applications for catechol.

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Bu Makaleye Atıf Yap

Demir, Z., Özkan, A., Sungur, B. (2025). Comparison of Catechol-Induced Expression Levels of ATM, ATR, BAX, BCL2, and CCND1 Genes Between Parental and Epirubicin-Resistant NSCLC Cells. European Journal of Biology, Volume: 84 Issue: 2. https://doi.org/10.26650/EurJBiol.2025.1612786

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Kaynakça (42)

  1. Adams JM, Cory S. The Bcl-2 apoptotic switch in cancer development and therapy. Oncogene. 2007;26(9):1324-1337. google scholar
  2. Bade BC, Dela Cruz CS. Lung Cancer 2020: Epidemiology, Etiology, and Prevention. Clin Chest Med. 2020;41(1):1-24. https://doi.org/10.1016/j.ccm.2019.10. 001 google scholar
  3. Balendiran K, Rao ST, Sekharudu CY, Zon G, Sundaralingam M. X-ray structures of the B-DNA dodecamer d(CGCGTTAACGCG) with an inverted central tetranucleotide and its netropsin complex. Acta Crystallogr D. 1995;51(2):190-198. google scholar
  4. Bijwaard KE, Aguilera NS, Monczak Y, Trudel M, Taubenberger JK, Lichy JH. Quantitative real-time reverse transcription-PCR assay for cyclin D1 expression: Utility in the diagnosis of mantle cell lymphoma. Clin Chem. 2001;47(2):195-201. google scholar
  5. Brian SC, Rick GS. Cisplatin-induced renal cell apoptosis: Caspase 3-dependent and -independent pathways. J Pharmacol Exp Ther. 2002;302(1):8. doi:10.1124/ jpet.302.1.8 google scholar
  6. Chen Z, Fillmore CM, Hammerman PS, Kim CF, Wong KK. Non-small-cell lung cancers: A heterogeneous set of diseases. Nat Rev Cancer. 2014;14(8):535-546. google scholar
  7. de Oliveira DM, Pitanga BP, Grangeiro MS, Lima RM, Costa MF, Costa SL, et al. Catechol cytotoxicity in vitro: Induction of glioblastoma cell death by apoptosis. Hum Exp Toxicol. 2010;29(3):199-212. google scholar
  8. de Sousa VML, Carvalho L. Heterogeneity in lung cancer. Pathobiol. 2018;85(1-2):96-107. google scholar
  9. Drew HR, Wing RM, Takano T, et al. Structure of a B-DNA dodecamer: Conformation and dynamics. Proc Natl Acad Sci. 1981;78(4):2179-2183. google scholar
  10. Eberhardt J, Santos-Martins D, Tillack AF, Forli S. AutoDock Vina 1.2.0: New docking methods, expanded force field, and python bindings. J Chem Inf Model. 2021;61(8):3891-3898. google scholar
  11. George VC, Ansari SA, Chelakkot VS, et al. DNA-dependent protein kinase: Epigenetic alterations and the role in genomic stability of cancer. Mutat Res Rev Mutat Res. 2019;780:92-105. google scholar
  12. George VC, Dellaire G, Rupasinghe HPV. Plant flavonoids in cancer chemoprevention: Role in genome stability. J Nutr Biochem. 2017;45:1-14. doi:10.1016/j.jnutbio.2016.11.007 google scholar
  13. George VC, Naveen Kumar DR, Suresh PK, Kumar S, Kumar RA. Comparative studies to evaluate relative in vitro potency of luteolin in inducing cell cycle arrest and apoptosis in HaCaT and A375 cells. Asian Pac J Cancer Prev. 2013;14(2):631-637. google scholar
  14. Gloeckner H, Jonuleit T, Lemke HD. Monitoring of cell viability and cell growth in a hollow-fiber bioreactor by use of the dye Alamar Blue. J Immunol Methods. 2001;252(1-2):131-138. google scholar
  15. Jiao M, Pirozzi CJ, Yu C, et al. Targeting catechol-o-methyltransferase induces mitochondrial dysfunction and enhances the efficacy of radiotherapy in glioma. Cancer Res. 2024;84(21):3640-3656. google scholar
  16. Suvarna V, Murahari M, Khan T, Chaubey P, Sangave P. Phytochemicals and PI3K inhibitors in cancer-an insight. Front Pharmacol. 2017;8:916. doi: 10.3389/ fphar.2017.00916 google scholar
  17. Huang ST, Yang RC, Yang LJ, Lee PN, Pang JH. Phyllanthus urinaria triggers the apoptosis and Bcl-2 down-regulation in Lewis lung carcinoma cells. Life Sci. 2003;72(15):1705-1716. google scholar
  18. Inamura K. Lung cancer: Understanding its molecular pathology and the 2015 WHO Classification. Front Oncol. 2017;7:193. doi:10.3389/fonc.2017.00193 google scholar
  19. Irwin JJ, Tang KG, Young J, Dandarchuluun C, Wong BR, Khurelbaatar M, ZINC20 —A free ultralarge-scale chemical database for ligand discovery. J Chem Inf Model. 2020;60(12):6065-6073. google scholar
  20. Lim do Y, Shin SH, Lee MH, et al. A natural small molecule, catechol, induces c-Myc degradation by directly targeting ERK2 in lung cancer. Oncotarget. 2016;7(23):35001-35014. google scholar
  21. McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol, 2013;5(4):a008656. doi:10.1101/ cshperspect.a008656 google scholar
  22. Moo-Puc R, Caamal-Fuentes E, Peraza-Sánchez SR, et al. Antiproliferative and antiestrogenic activities of bonediol an alkyl catechol from Bonellia macrocarpa. Biomed Res Int. 2015;847457. doi:10.1155/2015/847457 google scholar
  23. Nair PK, Melnick SJ, Wnuk SF, Rapp M, Escalon E, Ramachandran C. Isolation and characterization of an anticancer catechol compound from Semecarpus anacardium. J Ethnopharmacol. 2009;122(3):450-456. google scholar
  24. O'Boyle NM, Banck M, James CA, Morley C, Vandermeersch T, Hutchison GR. Open Babel: An open chemical toolbox. J Cheminform. 2011;3:33. doi:10.1186/1758-2946-3-33 google scholar
  25. Oikawa S, Hirosawa I, Hirakawa K, Kawanishi S. Site specificity and mechanism of oxidative DNA damage induced by carcinogenic catechol. Carcinogenesis. 2001;22(8):1239-1245. google scholar
  26. Ozkan A. Lymphokine-activated killer cell susceptibility in epirubicin-resistant and parental human non-small cell lung cancer (NSCLC). Biologia. 2007;62(2):232-237. google scholar
  27. Öztürk Ş, Duran N. Antiproliferative effects of Origanum syriacum L. and Myrtus communis L. on human colon cancer cell line. International Conference on Advanced Materials and Systems (ICAMS), 2018. google scholar
  28. Punia R, Raina K, Agarwal R, Singh RP. Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells. PLoS One. 2017;12(8):e0182870. doi:10.1371/journal.pone.0182870 google scholar
  29. Razak NA, Abu N, Ho WY, et al. Cytotoxicity of eupatorin in MCF-7 and MDA-MB-231 human breast cancer cells via cell cycle arrest, anti-angiogenesis and induction of apoptosis. Sci Rep. 2019;9(1):1514. doi:10.1038/s41598-018-37796-w google scholar
  30. Schweigert N, Zehnder AJB, Eggen RIL. Chemical properties of catechols and their molecular modes of toxic action in cells, from microorganisms to mammals. Environ Microbiol. 2001;3(2):81-91. google scholar
  31. Siddiqui SS, Rahman S, Rupasinghe HPV, Vazhappilly CG. Dietary Flavonoids in p53-mediated immune dysfunctions linking to cancer prevention. Biomedicines. 2020;8(8). doi:10.3390/biomedicines8080286 google scholar
  32. Silva VR, Corrêa RS, Santos LS, Soares MBP, Batista AA, Bezerra DP. A ruthenium-based 5-fluorouracil complex with enhanced cytotoxicity and apoptosis induction action in HCT116 cells. Sci Rep. 2018;8(1):288. doi:10.1038/ s41598-017-18639-6 google scholar
  33. SPSS, I. 2022. IBM SPSS. https://www.ibm.com/products/spss-statistics google scholar
  34. Statistic C. 2022. Cancer statistics. retrieved 10.05.2022 from https://hsgm.saglik. gov.tr/tr/kanser-istatistikleri. google scholar
  35. Trott O, Olson AJ. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem. 2010;31(2):455-461. google scholar
  36. Vazhappilly CG, Hodeify R, Siddiqui SS, et al. Natural compound catechol induces DNA damage, apoptosis, and G1 cell cycle arrest in breast cancer cells. Phytother Res. 2021;35(4):2185-2199. google scholar
  37. Vazhappilly CG, Ansari SA, Al-Jaleeli R, et al. Role of flavonoids in thrombotic, cardiovascular, and inflammatory diseases. Inflammopharmacology. 2019;27(5):863-869. google scholar
  38. Vazhappilly CG, Saleh E, Ramadan W, et al. Inhibition of SHP2 by new compounds induces differential effects on RAS/RAF/ERK and PI3K/AKT pathways in different cancer cell types. Invest New Drugs. 2019;37(2):252-261. google scholar
  39. Wadood A, Riaz M, Jamal SB, Shah M, Lodhi MA. Molecular docking study of P4-Benzoxaborolesubstituted ligands as inhibitors of HCV NS3/4A protease. Bioinformation. 2013;9(6):309-314. google scholar
  40. Warren CFA, Wong-Brown MW, Bowden NA. BCL-2 family isoforms in apoptosis and cancer. Cell Death Dis. 2019;10(3):177. doi:10.1038/s41419-019-1407-6 google scholar
  41. Bolton JL, Dunlap T. Formation and biological targets of quinones: Cytotoxic versus cytoprotective effects. Chem Res Toxicol. 2017;30(1):13-37. google scholar
  42. El-Bachá RS. Cytotoxic effects of catechols to glial and neuronal cells. Conference Abstract: Latin-American School on glial cells in the diseased brain (IBRO). 2015. doi:10.3389/conf.fncel.2015.35.00011 google scholar