Exploring Cytotoxic and Apoptotic Effects of Rosuvastatin on Lung Cancer Cell Line
DOI:
https://doi.org/10.22317/jcms.v11i1.1696Keywords:
Rosuvastatin, Anticancer, lung cancer, Caspase-3Abstract
Objectives: This study aimed to investigate the efficacy of Rosuvastatin (Ros) in inhibiting lung cancer cell proliferation in compared to standard treatment, doxorubicin (Dox).
Methods: A549 cells were divided into four groups (untreated (control), Dox-treated, and Ros-treated cells) and subjected to six concentrations of the tested drugs. After 72 hours, the cytotoxicity and IC50 concentrations of each drug were determined. A549 cells were then subjected to the IC50 concentrations of either Ros or Dox or left untreated. The cell pellets were tested for caspase 3. Acridine orange/ethidium bromide stain was used to visualize and calculate apoptotic cells
Results: Our results indicated that Ros treatment caused a significant decline in percentage of cellular growth when compared to control group with an IC50 of 45.24 μg/ml. While for Dox treated cells, only the highest concentration produced a significant reduction in percentage of cellular growth compared to control, with an estimated IC50 of 294.2 μg/ml. Furthermore, Ros caused a significant elevation in caspase 3 level compared to control. The same effect was nearly observed in Dox-treated cells with no significant difference between them. Additionally, cells treated with Ros exerted a higher percentage of apoptosis compared to control. For Dox treated cells, the percentage of apoptosis was lower than that of Ros, however; this effect was statistically non-significant.
Conclusion: our findings confirmed that rosuvastatin suppressed the growth of lung cancer cells by triggering apoptosis via a caspase 3 dependent mechanism
Keywords; Rosuvastatin, anticancer, lung cancer, caspase 3
References
Cruz CS Dela, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med. 2011;32(4):605–44.
Lai C-R, Tsai Y-L, Tsai W-C, Chen T-M, Chang H-H, Changchien C-Y, et al. Farnesoid X Receptor Overexpression Decreases the Migration, Invasion and Angiogenesis of Human Bladder Cancers via AMPK Activation and Cholesterol Biosynthesis Inhibition. Vol. 14, Cancers. 2022.
Hajdúch M, KoIek V. Drug resistance in lung cancer. Cancer Ther. 2008;6(2).
Wang M, Herbst RS, Boshoff C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat Med [Internet]. 2021;27(8):1345–56. Available from: https://doi.org/10.1038/s41591-021-01450-2
Han YH, Park WH. Growth inhibition in antimycin A treated-lung cancer Calu-6 cells via inducing a G1 phase arrest and apoptosis. Lung cancer. 2009;65(2):150–60.
Jabir AA, Alzubaidy AA, Kadhim HS. Effects of Black Seed on Lung Cancer/in Vitro Study. Med J Babylon. 2015;12(2).
Chimento A, Casaburi I, Avena P, Trotta F, De Luca A, Rago V, et al. Cholesterol and its metabolites in tumor growth: therapeutic potential of statins in cancer treatment. Front Endocrinol (Lausanne). 2019;9:807.
Luo J, Yang H, Song B-L. Mechanisms and regulation of cholesterol homeostasis. Nat Rev Mol cell Biol. 2020;21(4):225–45.
Wei M, Nurjanah U, Herkilini A, Huang C, Li Y, Miyagishi M, et al. Unspliced XBP1 contributes to cholesterol biosynthesis and tumorigenesis by stabilizing SREBP2 in hepatocellular carcinoma. Cell Mol Life Sci. 2022;79(9):472.
Wang L, Ruan Y, Wu X, Zhou X. lncRNA ZFAS1 promotes HMGCR mRNA stabilization via binding U2AF2 to modulate pancreatic carcinoma lipometabolism. J Immunol Res. 2022;2022(1):4163198.
Yuan H, Wu H, Cheng J, Xiong J. SIAH1 ubiquitination-modified HMGCR inhibits lung cancer progression and promotes drug sensitivity through cholesterol synthesis. Cancer Cell Int [Internet]. 2023;23(1):71. Available from: https://doi.org/10.1186/s12935-023-02914-w
Al-Thamir SNK, Al-Shalah HH, Bairam AFH. Protection from the Acute Cisplatin-Induced Nephrotoxicity by Simvastatin in Rats. Med J Babylon. 2012;9(1):51–9.
Oh J, Lee BS, Lim G, Lim H, Lee CJ, Park S, et al. Atorvastatin protects cardiomyocyte from doxorubicin toxicity by modulating survivin expression through FOXO1 inhibition. J Mol Cell Cardiol. 2020;138:244–55.
Gewirtz D. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999;57(7):727–41.
Shandilya M, Sharma S, Das PP, Charak S. Molecular-Level Understanding of the Anticancer Action Mechanism of Anthracyclines. In: Arnouk H, Hassan BAR, editors. Rijeka: IntechOpen; 2020. p. Ch. 9. Available from: https://doi.org/10.5772/intechopen.94180
Fuchs Y, Steller H. Programmed cell death in animal development and disease. Cell. 2011;147(4):742–58.
Wong RSY. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin cancer Res. 2011;30:1–14.
Mi J, Zhang X, Rabbani ZN, Liu Y, Reddy SK, Su Z, et al. RNA aptamer-targeted inhibition of NF-κB suppresses non-small cell lung cancer resistance to doxorubicin. Mol Ther. 2008;16(1):66–73.
Zeybek ND, Gulcelik NE, Kaymaz FF, Sarisozen C, Vural I, Bodur E, et al. Rosuvastatin induces apoptosis in cultured human papillary thyroid cancer cells. J Endocrinol [Internet]. 2011;210(1):105–15. Available from: https://joe.bioscientifica.com/view/journals/joe/210/1/105.xml
Freshney RI. Subculture and cell lines. Cult Anim cells a Man basic Tech. 2005;
van Meerloo J, Kaspers GJL, Cloos J. Cell Sensitivity Assays: The MTT Assay BT - Cancer Cell Culture: Methods and Protocols. In: Cree IA, editor. Totowa, NJ: Humana Press; 2011. p. 237–45. Available from: https://doi.org/10.1007/978-1-61779-080-5_20
He Y, Zhu Q, Chen M, Huang Q, Wang W, Li Q, et al. The changing 50% inhibitory concentration (IC 50 ) of cisplatin: a pilot study on the artifacts of the MTT assay and the precise measurement of density-dependent chemoresistance in ovarian cancer. Oncotarget; Vol 7, No 43 [Internet]. 2016; Available from: https://www.oncotarget.com/article/12223/text/
Jabir AA-H, Kadhim HS, Alzubaidy AA. Effects of fenugreek on lung cancer/in vitro study. Chemotherapy. 2015;3(2):4.
Sulaiman GM, Waheeb HM, Jabir MS, Khazaal SH, Dewir YH, Naidoo Y. Hesperidin Loaded on Gold Nanoparticles as a Drug Delivery System for a Successful Biocompatible, Anti-Cancer, Anti-Inflammatory and Phagocytosis Inducer Model. Sci Rep [Internet]. 2020;10(1):9362. Available from: https://doi.org/10.1038/s41598-020-66419-6
Helmy IM, Abdel Azim AM. Efficacy of ImageJ in the assessment of apoptosis. Diagn Pathol [Internet]. 2012;7(1):15. Available from: https://doi.org/10.1186/1746-1596-7-15
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018. CA Cancer J Clin. 2018;68(1):7–30.
Ma X, Liang A-L, Liu Y-J. Research progress on the relationship between lung cancer drug-resistance and microRNAs. J Cancer. 2019;10(27):6865.
Kuczynski EA, Reynolds AR. Vessel co-option and resistance to anti-angiogenic therapy. Angiogenesis. 2020;23(1):55–74.
Jafari M, Rezaei M, Kalantari H, Hashemitabar M. Determination of cell death induced by lovastatin on human colon cell line HT29 using the comet assay. Jundishapur J Nat Pharm Prod. 2013;8(4):187.
Walther U, Emmrich K, Ramer R, Mittag N, Hinz B. Lovastatin lactone elicits human lung cancer cell apoptosis via a COX-2/PPARγ-dependent pathway. Oncotarget. 2016;7(9):10345.
Kesavardhana S, Malireddi RKS, Kanneganti T-D. Caspases in cell death, inflammation, and pyroptosis. Annu Rev Immunol. 2020;38(1):567–95.
Ray P, De A, Patel M, Gambhir SS. Monitoring Caspase-3 Activation with a Multimodality Imaging Sensor in Living Subjects. Clin Cancer Res [Internet]. 2008 Sep 14;14(18):5801–9. Available from: https://doi.org/10.1158/1078-0432.CCR-07-5244
Friedrich K, Wieder T, Von Haefen C, Radetzki S, JaÈnicke R, Schulze-Osthoff K, et al. Overexpression of caspase-3 restores sensitivity for drug-induced apoptosis in breast cancer cell lines with acquired drug resistance. Oncogene. 2001;20(22):2749–60.
Liu J-C, Yang T-Y, Hsu Y-P, Hao W-R, Kao P-F, Sung L-C, et al. Statins dose-dependently exert a chemopreventive effect against lung cancer in COPD patients: a population-based cohort study. Oncotarget. 2016;7(37):59618.
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Journal of Contemporary Medical Sciences
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
