Oxidative Stress Mediates Anti-proliferative Effects of Nifedipine on AGS Cells

Zıad Joha; Sude Nur Göksu

doi:10.17776/csj.1535242

EN

Oxidative Stress Mediates Anti-proliferative Effects of Nifedipine on AGS Cells

Abstract

Previous studies have demonstrated the anticancer properties of certain calcium channel blockers when administered as sole agents. This exploration aimed to explore the potential anti-proliferative activity of nifedipine on AGS gastric cancer cells and to determine the contribution of oxidative stress in mediating this response. To assess the anti-proliferative impact of nifedipine, AGS cell viability was calculated employing the XTT assay across a concentration range of 25, 50, 100, 200, and 500 µg/mL. Concurrently, TAS and TOS kits were employed to evaluate the drug's influence on oxidative stress levels. Nifedipine exhibited a concentration-dependent cytotoxic effect on AGS cells, with a statistically significant reduction in cell viability. The IC50 value for AGS cells after 24 hours was determined to be 98.49 µg/mL. At this concentration, a substantial augmentation in TOS and a concurrent diminution in TAS levels were observed relative to the control group. These observations imply that nifedipine-induced oxidative stress is one of the mechanisms underlying its cytotoxic action against gastric cancer cells. Our results highlight the potential therapeutic utility of nifedipine in this cancer type.

Keywords

Supporting Institution

TÜBİTAK

Project Number

1919B012221382

References

[1] Ergül M., T-type Calcium Channel Blocker, NNC 55-0396, Suppress Cell Proliferation and Promote Apoptosis in SNU-1 Gastric Cancer Cells, Cumhuriyet Science Journal, 44 (2023) 254–7.
[2] Joshi SS, Badgwell BD., Current treatment and recent progress in gastric cancer., A Cancer Journal for Clinicians, 71 (2021) 264–79.
[3] Harada K, Sakamoto N, Ukai S, Yamamoto Y, Pham QT, Taniyama D, et al., Establishment of oxaliplatin-resistant gastric cancer organoids: importance of myoferlin in the acquisition of oxaliplatin resistance, Gastric Cancer,24 (2021) 1264–77.
[4] Gonçalves JCR, Coulidiati TH, Monteiro AL, de Carvalho-Gonçalves LCT, de Oliveira Valença W, de Oliveira RN, et al., Antitumoral activity of novel 1,4-naphthoquinone derivative involves L-type calcium channel activation in human colorectal cancer cell line. Journal of Applied Biomedicine, 14 (2016) 229–34.
[5] Monteith GR, Davis FM, Roberts-Thomson SJ., Calcium channels and pumps in cancer: Changes and consequences, Journal of Biological Chemistry,287 (2012) 31666–73.
[6] Wu L, Lin W, Liao Q, Wang H, Lin C, Tang L, et al., Calcium Channel Blocker Nifedipine Suppresses Colorectal Cancer Progression and Immune Escape by Preventing NFAT2 Nuclear Translocation, Cell Reports, 33 (2020) 108327.
[7] Wu L, Lian W, Zhao L., Calcium signaling in cancer progression and therapy, The FEBS Journal, 288 (2021) 6187–205.
[8] Phan NN, Wang C-Y, Chen C-F, Sun Z, Lai M-D, Lin Y-C., Voltage-gated calcium channels: Novel targets for cancer therapy, Oncology Letters 14 (2) (2017) 2059–74.

[9] Ferrari R, Pavasini R, Camici PG, Crea F, Danchin N, Pinto F, et al., Anti-anginal drugs–beliefs and evidence: systematic review covering 50 years of medical treatment, European Heart Journal, 40 (2019) 190–4.
[10] Kondo S, Yin D, Morimura T, Kubo H, Nakatsu S, Takeuchi J., Combination therapy with cisplatin and nifedipine induces apoptosis in cisplatin-sensitive and cisplatin-resistant human glioblastoma cells, British Journal of Cancer, 71 (1995) 282–9.
[11] Chiu LY, Ko JL, Lee YJ, Yang TY, Tee YT, Sheu GT., L-type calcium channel blockers reverse docetaxel and vincristine-induced multidrug resistance independent of ABCB1 expression in human lung cancer cell lines, Toxicology Letters,192 (2010) 408–18.
[12] Guo R, Huang X, Jin X, Yang J., Diltiazem inhibits proliferation and motility of hepatocellular cells in vitro by downregulating calcium-activated chloride channel TMEM16A, Journal of Southern Medical University, 38 (2018) 818–23.
[13] Panneerpandian P, Rao DB, Ganesan K., Calcium channel blockers lercanidipine and amlodipine inhibit YY1/ERK/TGF-β mediated transcription and sensitize the gastric cancer cells to doxorubicin, Toxicology in Vitro, 74 (2021) 105152
[14] Yang JL, Friedlander ML., Effect of nifedipine in metastatic colon cancer with DNA mismatch repair gene defect. The Lancet, 357 (9270) (2001) 1767-1768.
[15] Taştemur Ş, Hacısüleyman L, Karataş Ö, Yulak F, Ataseven H. Anticancer activity of sinapic acid by inducing apoptosis in HT-29 human colon cancer cell line, Canadian Journal of Physiology and Pharmacology 101 (7) (2023) 361-368.
[16] Ataseven D, Taştemur Ş, Yulak F, Karabulut S, Ergul M, GSK461364A suppresses proliferation of gastric cancer cells and induces apoptosis, Toxicology in Vitro, 90 (2023) 105610
[17] Ciltas AC, Karabulut S, Sahin B, Filiz AK, Yulak F, Ozkaraca M, et al., FGF-18 alleviates memory impairments and neuropathological changes in a rat model of Alzheimer’s disease, Neuropeptides 101 (2023) 102367.
[18] Yulak F, Filiz AK, Joha Z, Ergul M., Mechanism of anticancer effect of ETP-45658, a PI3K/AKT/mTOR pathway inhibitor on HT-29 Cells, Medical Oncology, 40 (2023) 1–14.
[19] Erel O., A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation, Clinical Biochemistry, 37 (2004) 277–85.
[20] Taskiran AS, Ergul M, Gunes H, Ozturk A, Sahin B, Ozdemir E., The Effects of Proton Pump Inhibitors (Pantoprazole) on Pentylenetetrazole-Induced Epileptic Seizures in Rats and Neurotoxicity in the SH-SY5Y Human Neuroblastoma Cell Line, Cellular and Molecular Neurobiology, 41 (2021) 173–83.
[21] Erel O., A new automated colorimetric method for measuring total oxidant status. Clinical Biochemistry, 38 (2005) 1103–11.
[22] Tastemur Y, Gumus E, Ergul M, Ulu M, Akkaya R, Ozturk A, et al., Positive effects of angiotensin-converting enzyme (ACE) inhibitor, captopril, on pentylenetetrazole-induced epileptic seizures in mice, Tropical Journal of Pharmaceutical Research, 19 (2020) 637–43.
[23] Dziegielewska B, Gray LS, Dziegielewski J., T-type calcium channels blockers as new tools in cancer therapies, Pflugers Archiv European Journal of Physiology, 466 (2014) 801–10.
[24] Li M, Ruan B, Wei J, Yang Q, Chen M, Ji M, et al., ACYP2 contributes to malignant progression of glioma through promoting Ca2+efflux and subsequently activating c-Myc and STAT3 signals, Journal of Experimental and Clinical Cancer Research, 39 (2020) 1–14.
[25] Henderson VM, Hawsawi O, Burton LJ, Campbell T, Trice K, Dougan J, et al., Cancer-bone microenvironmental interactions promotes STAT3 signaling, Molecular Carcinogenesis, 58 (2019) 1349–61.
[26] Li L, Zhang R, Liu Y, Zhang G., ANXA4 Activates JAK-STAT3 Signaling by Interacting with ANXA1 in Basal-Like Breast Cancer, DNA and Cell Biology, 39 (2020) 1649–56.
[27] Li QT, Feng YM, Ke ZH, Qiu MJ, He XX, Wang MM, et al., KCNN4 Promotes Invasion and Metastasis through the MAPK/ERK Pathway in Hepatocellular Carcinoma, J Investig Med., 68 (2020) 68–74.
[28] Hamilton G, Theyer G, Baumgartner G., Calcium antagonists as modulators of multi-drug resistant tumor cells. Wiener Medizinische Wochenschrift, 143 (1993) 526–32.
[29] Yu DS, Ma CP, Chang SY., Verapamil modulation of multidrug resistance in renal cell carcinoma, Journal of the Formosan Medical Association, 99 (2000) 311–6.
[30] Zheng W, Li M, Lin Y, Zhan X., Encapsulation of verapamil and doxorubicin by MPEG-PLA to reverse drug resistance in ovarian cancer, Biomedicine & Pharmacotherapy, 108 (2018) 565–73..
[31] [31] Guo R, Jin X, Tian Y, Huang X, Li Z, Yang J., Calcium channel blocker diltizem transiently inhibits migration and up-regulates metadherin expression in hepatocellular carcinoma cells in vitro, Journal of Southern Medical University,39 (2019) 298–303.
[32] Matos CP, Adiguzel Z, Yildizhan Y, Cevatemre B, Onder TB, Cevik O, et al., May iron(III) complexes containing phenanthroline derivatives as ligands be prospective anticancer agents?, European Journal of Medic00000inal Chemistry, 176 (2019) 492–512.
[33] Yulak F, Üngür B., Investigation of the Effect of Indatraline on Oxidative Damage Induced by Hydrogen Peroxide in C6 Glioma Cell Line, Cumhuriyet Science Journal, 44 (2023) 645–9.
[34] Çiltaş AÇ, Gündoğdu S, Yulak F., Levetiracetam Protects Against Glutamate-Induced Excitotoxicity in SH-SY5Y Cell Line, International Journal of Nature and Life Sciences, 6 (2022)142–50.

Details

Primary Language

English

Subjects

Basic Pharmacology

Journal Section

Research Article

Authors

Zıad Joha ^*
0000-0001-8520-3760
Türkiye

Sude Nur Göksu
0009-0007-9021-2021
Türkiye

Publication Date

December 30, 2024

Submission Date

August 18, 2024

Acceptance Date

December 16, 2024

Published in Issue

Year 2024 Volume: 45 Number: 4

DOI

https://doi.org/10.17776/csj.1535242

IZ

https://izlik.org/JA85HL56CT

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RIS / Bibtex

APA

Joha, Z., & Göksu, S. N. (2024). Oxidative Stress Mediates Anti-proliferative Effects of Nifedipine on AGS Cells. Cumhuriyet Science Journal, 45(4), 683-687. https://doi.org/10.17776/csj.1535242

Öz

Oxidative Stress Mediates Anti-proliferative Effects of Nifedipine on AGS Cells

Abstract

Keywords

Supporting Institution

Project Number

References

Details

Primary Language

Subjects

Journal Section

Authors

Publication Date

Submission Date

Acceptance Date

Published in Issue

DOI

IZ

Cite