Enhancement of apoptosis in Caco-2, Hep-G2, and HT29 cancer cell lines following exposure to Toxoplasma gondii peptides
DOI:
https://doi.org/10.33393/dti.2024.3177Keywords:
Anticancer, Neoplasm, Parasite, Peptides, Real-time PCR, ToxoplasmosisAbstract
Objective: Cancer or neoplasm is a cosmopolitan catastrophe that results in more than 20 million new cases and 10 million deaths every year. Some factors lead to carcinogenesis like infectious diseases. Parasites like Toxoplasma gondii, by its components, could modulate the cancer system by inducing apoptosis. The objective of this investigation is to assess the potential of peptides derived from T. gondii in combating cancer by examining their effects on Caco-2, Hep-G2, and HT29 cell lines.
Materials and methods: Candidate peptide by its similarity to anticancer compounds was predicted through the computer-based analysis/platform. The impact of the peptide on cell viability, cell proliferation, and gene expression was evaluated through the utilization of MTT assay, flow cytometry, and real-time polymerase chain reaction (PCR) methodologies.
Results: The cell viability rate exhibited a significant decrease (p < 0.001) across all cell lines when exposed to a concentration of ≤160 μg. Within the 48-hour timeframe, the half maximal inhibitory concentration (IC50) for HT29 and Hep-G2 cell lines was determined to be 107.2 and 140.6 μg/mL, respectively. Notably, a marked decrease in the expression levels of Bcl2 and APAF1 genes was observed in both the Hep-G2 and HT29 cell lines.
Conclusion: These findings indicate that the T. gondii peptide affected cancer cell mortality and led to changes in the expression of genes associated with apoptosis.
Downloads
References
Flegr J, Prandota J, Sovičková M, Israili ZH. Toxoplasmosis – a global threat. Correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS One. 2014;9(3):e90203. PMID:24662942 https://doi.org/10.1371/journal.pone.0090203 PMID:24662942
Dubey JP. History of the discovery of the life cycle of Toxoplasma gondii. Int J Parasitol. 2009;39(8):877-882. PMID:19630138 https://doi.org/10.1016/j.ijpara.2009.01.005 PMID:19630138
Attias M, Teixeira DE, Benchimol M, Vommaro RC, Crepaldi PH, De Souza W. The life-cycle of Toxoplasma gondii reviewed using animations. Parasit Vectors. 2020;13(1):588. https://doi.org/10.1186/s13071-020-04445-z PMID:33228743
Stelzer S, Basso W, Benavides Silván J, et al. Toxoplasma gondii infection and toxoplasmosis in farm animals: risk factors and economic impact. Food Waterborne Parasitol. 2019;15:e00037. https://doi.org/10.1016/j.fawpar.2019.e00037 PMID:32095611
Dubey JP. The history and life cycle of Toxoplasma gondii. In: Weiss LM, Kim K, eds. Toxoplasma gondii. Elsevier 2020; 1-19. https://doi.org/10.1016/B978-0-12-815041-2.00001-3
Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011 Mar 4;144(5):646-74. doi: 10.1016/j.cell.2011.02.013. PMID: 21376230.
Callejas BE, Martínez-Saucedo D, Terrazas LI. Parasites as negative regulators of cancer. Biosci Rep. 2018;38(5):BSR20180935. https://doi.org/10.1042/BSR20180935 PMID:30266743
Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. https://doi.org/10.3322/caac.21660 PMID:33538338
Knoll LJ, Hogan DA, Leong JM, Heitman J, Condit RC. Pearls collections: What we can learn about infectious disease and cancer. Public Library of Science San Francisco 2018; e1006915.
Bahadory S, Sadraei J, Zibaei M, Pirestani M, Dalimi A. In vitro anti-gastrointestinal cancer activity of Toxocara canis-derived peptide: analyzing the expression level of factors related to cell proliferation and tumor growth. Front Pharmacol. 2022;13:878724. https://doi.org/10.3389/fphar.2022.878724 PMID:36204226
Fox BA, Butler KL, Guevara RB, Bzik DJ. Cancer therapy in a microbial bottle: uncorking the novel biology of the protozoan Toxoplasma gondii. PLoS Pathog. 2017;13(9):e1006523. https://doi.org/10.1371/journal.ppat.1006523 PMID:28910406
Soleimani M, Nadri S. A protocol for isolation and culture of mesenchymal stem cells from mouse bone marrow. Nat Protoc. 2009;4(1):102-106. https://doi.org/10.1038/nprot.2008.221 PMID:19131962
Kumar P, Nagarajan A, Uchil PD. Analysis of cell viability by the MTT assay. Cold Spring Harb Protoc. 2018;2018(6):pdb.prot095505. https://doi.org/10.1101/pdb.prot095505 PMID:29858338
Pan W, Yang J, Wei J, et al. Functional BCL-2 regulatory genetic variants contribute to susceptibility of esophageal squamous cell carcinoma. Sci Rep. 2015;5(1):11833. https://doi.org/10.1038/srep11833 PMID:26132559
Shang J, Yang F, Wang Y, et al. MicroRNA-23a antisense enhances 5-fluorouracil chemosensitivity through APAF-1/caspase-9 apoptotic pathway in colorectal cancer cells. J Cell Biochem. 2014;115(4):772-784. https://doi.org/10.1002/jcb.24721 PMID:24249161
McKinnon KM. Flow cytometry: an overview. Curr Protoc Immunol. 2018;120(1):5.1.1-5.1.11. https://doi.org/10.1002/cpim.40
Lin SR, Chang CH, Hsu CF, et al. Natural compounds as potential adjuvants to cancer therapy: preclinical evidence. Br J Pharmacol. 2020;177(6):1409-1423. https://doi.org/10.1111/bph.14816 PMID:31368509
Zheng H-C. The molecular mechanisms of chemoresistance in cancers. Oncotarget. 2017;8(35):59950-59964. https://doi.org/10.18632/oncotarget.19048 PMID:28938696
Chen M-L, Lai C-J, Lin Y-N, Huang C-M, Lin Y-H. Multifunctional nanoparticles for targeting the tumor microenvironment to improve synergistic drug combinations and cancer treatment effects. J Mater Chem B. 2020;8(45):10416-10427. https://doi.org/10.1039/D0TB01733G PMID:33112350
Garcia SB, Aranha AL, Garcia FRB, et al. A retrospective study of histopathological findings in 894 cases of megacolon: what is the relationship between megacolon and colonic cancer? Rev Inst Med Trop São Paulo. 2003;45(2):91-93. https://doi.org/10.1590/S0036-46652003000200007 PMID:12754574
Hunter CA, Subauste CS, Van Cleave VH, Remington JS. Production of gamma interferon by natural killer cells from Toxoplasma gondii-infected SCID mice: regulation by interleukin-10, interleukin-12, and tumor necrosis factor alpha. Infect Immun. 1994;62(7):2818-2824. https://doi.org/10.1128/iai.62.7.2818-2824.1994 PMID:7911785
Fosgerau K, Hoffmann T. Peptide therapeutics: current status and future directions. Drug Discov Today. 2015;20(1):122-128. https://doi.org/10.1016/j.drudis.2014.10.003 PMID:25450771
Lv S, Sylvestre M, Prossnitz AN, Yang LF, Pun SH. Design of polymeric carriers for intracellular peptide delivery in oncology applications. Chem Rev. 2021;121(18):11653-11698. https://doi.org/10.1021/acs.chemrev.0c00963 PMID:33566580
Gogvadze V, Orrenius S, Zhivotovsky B. Multiple pathways of cytochrome c release from mitochondria in apoptosis. Biochim Biophys Acta. 2006;1757(5-6):639-647. https://doi.org/10.1016/j.bbabio.2006.03.016 PMID:16678785
Brunelle JK, Letai A. Control of mitochondrial apoptosis by the Bcl-2 family. J Cell Sci. 2009;122(Pt 4):437-441. https://doi.org/10.1242/jcs.031682 PMID:19193868
Shakeri R, Kheirollahi A, Davoodi J. Apaf-1: regulation and function in cell death. Biochimie. 2017;135:111-125. https://doi.org/10.1016/j.biochi.2017.02.001 PMID:28192157
Tang D, Kang R, Berghe TV, Vandenabeele P, Kroemer G. The molecular machinery of regulated cell death. Cell Res. 2019;29(5):347-364. https://doi.org/10.1038/s41422-019-0164-5 PMID:30948788
D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int. 2019;43(6):582-592. https://doi.org/10.1002/cbin.11137 PMID:30958602
Robles AI, Bemmels NA, Foraker AB, Harris CC. APAF-1 is a transcriptional target of p53 in DNA damage-induced apoptosis. Cancer research. 2001 Sep 15;61(18):6660-4.
Liu L, Yuan G, Cheng Z, Zhang G, Liu X, Zhang H. Identification of the mRNA expression status of the dopamine D2 receptor and dopamine transporter in peripheral blood lymphocytes of schizophrenia patients. PLoS One. 2013;8(9):e75259. https://doi.org/10.1371/journal.pone.0075259 PMID:24086483
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 The Authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors contributing to Drug Target Insights agree to publish their articles under the Creative Common Attribution Non Commercial 4.0 (CC-BY-NC 4.0) license, which allows third parties to re-use the work without permission as long as the work is properly referenced and the use is non-commercial.
Accepted 2024-07-11
Published 2024-09-30