The anticancer effects of thymol on HepG2 cell line.
Apoptosis
Cytotoxicity
HepG2
Oxidative stress
Thymol
Journal
Medical oncology (Northwood, London, England)
ISSN: 1559-131X
Titre abrégé: Med Oncol
Pays: United States
ID NLM: 9435512
Informations de publication
Date de publication:
05 Aug 2023
05 Aug 2023
Historique:
received:
23
06
2023
accepted:
19
07
2023
medline:
7
8
2023
pubmed:
6
8
2023
entrez:
5
8
2023
Statut:
epublish
Résumé
There is an increasing incidence of liver cancer, which is a hazard for global health. The present study was designed to evaluate possible cytotoxic, genotoxic, apoptotic, oxidant and antioxidant effects of thymol on hepatocellular carcinoma (HepG2) cell line. The cytotoxic effect of thymol on HepG2 cell line was determined by XTT test. We also used the HUVEC cell line to show whether thymol damages healthy cells. Oxidative stress level was determined with Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) measurement kits. Apoptosis of cells was detected in flow cytometry with Annexin V apoptosis kit. Apoptotic gene expressions were analyzed by real-time PCR. Genotoxicity was determined by comet assay, which measures DNA damage. The thymol IC
Identifiants
pubmed: 37542527
doi: 10.1007/s12032-023-02134-2
pii: 10.1007/s12032-023-02134-2
doi:
Substances chimiques
Thymol
3J50XA376E
Antioxidants
0
Oxidants
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
260Subventions
Organisme : Pamukkale Üniversitesi
ID : 2021BSP009
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Villanueva A. Hepatocellular carcinoma. N Engl J Med. 2019;380:1450–62. https://doi.org/10.1056/NEJMra1713263 .
doi: 10.1056/NEJMra1713263
pubmed: 30970190
Cancer Today. https://gco.iarc.fr/today/online-analysis-pie?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=total&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&nb_items=7&group_cancer=1&include_nmsc=1&include_nmsc_other=1&half_pie=0&donut=0 . Accessed 31 Jan 2023.
Llovet JM, Kelley RK, Villanueva A, Singal AG, Pikarsky E, Roayaie S, et al. Hepatocellular carcinoma. Nat Rev Dis Primers. 2021. https://doi.org/10.1038/s41572-020-00240-3 .
doi: 10.1038/s41572-020-00240-3
pubmed: 33479224
Estes C, Razavi H, Loomba R, Younossi Z, Sanyal AJ. Modeling the epidemic of nonalcoholic fatty liver disease demonstrates an exponential increase in burden of disease. Hepatology. 2018;67:123–33. https://doi.org/10.1002/hep.29466 .
doi: 10.1002/hep.29466
pubmed: 28802062
Parham S, Kharazi AZ, Bakhsheshi-Rad HR, Nur H, Ismail AF, Sharif S, et al. Antioxidant, antimicrobial and antiviral properties of herbal materials. Antioxidants (Basel). 2020;9:1–36. https://doi.org/10.3390/antiox9121309 .
doi: 10.3390/antiox9121309
Kowalczyk A, Przychodna M, Sopata S, Bodalska A, Fecka I. Thymol and thyme essential oil-new ınsights into selected therapeutic applications. Molecules. 2020. https://doi.org/10.3390/molecules25184125 .
doi: 10.3390/molecules25184125
pubmed: 33266178
pmcid: 7730084
Salehi B, Mishra AP, Shukla I, Sharifi-Rad M, del Mar Contreras M, Segura-Carretero A, et al. Thymol, thyme, and other plant sources: health and potential uses. Phytother Res. 2018;32:1688–706. https://doi.org/10.1002/ptr.6109 .
doi: 10.1002/ptr.6109
pubmed: 29785774
Hashemipour H, Kermanshahi H, Golian A, Veldkamp T. Effect of thymol and carvacrol feed supplementation on performance, antioxidant enzyme activities, fatty acid composition, digestive enzyme activities, and immune response in broiler chickens. Poult Sci. 2013;92:2059–69.
doi: 10.3382/ps.2012-02685
pubmed: 23873553
Zarrini G, Delgosha ZB, Moghaddam KM, Shahverdi AR. Post-antibacterial effect of thymol. Pharm Biol. 2010;48:633–6.
doi: 10.3109/13880200903229098
pubmed: 20645735
Nieto G. Biological activities of three essential oils of the lamiaceae family. Medicines. 2017;4:63.
doi: 10.3390/medicines4030063
pubmed: 28930277
pmcid: 5622398
Horvathova E, Navarova J, Galova E, Sevcovicova A, Chodakova L, Snahnicanova Z, et al. Assessment of antioxidative, chelating, and DNA-Protective effects of selected essential oil components (Eugenol, Carvacrol, Thymol, Borneol, Eucalyptol) of plants and intact rosmarinus officinalis oil. J Agric Food Chem. 2014;62:6632–9.
doi: 10.1021/jf501006y
pubmed: 24955655
Liang D, Li F, Fu Y, Cao Y, Song X, Wang T, et al. Thymol inhibits LPS-stimulated inflammatory response via down-regulation of NF-κB and MAPK signaling pathways in mouse mammary epithelial cells. Inflammation. 2014;37:214–22.
doi: 10.1007/s10753-013-9732-x
pubmed: 24057926
Islam MT, Khalipha ABR, Bagchi R, Mondal M, Smrity SZ, Uddin SJ, et al. Anticancer activity of thymol: a literature-based review and docking study with Emphasis on its anticancer mechanisms. IUBMB Life. 2019;71:9–19. https://doi.org/10.1002/iub.1935 .
doi: 10.1002/iub.1935
pubmed: 30308112
Li Y, Wen J, Du C, Hu S, Chen J, Zhang S, et al. Thymol inhibits bladder cancer cell proliferation via inducing cell cycle arrest and apoptosis. Biochem Biophys Res Commun. 2017;491:530–6. https://doi.org/10.1016/j.bbrc.2017.04.009 .
doi: 10.1016/j.bbrc.2017.04.009
pubmed: 28389245
De La Chapa JJ, Singha PK, Lee DR, Gonzales CB. Thymol inhibits oral squamous cell carcinoma growth via mitochondria-mediated apoptosis. J Oral Pathol Med. 2018;47:674–82. https://doi.org/10.1111/jop.12735 .
doi: 10.1111/jop.12735
pubmed: 29777637
Hassan HFH, Mansour AM, Salama SA, El-Sayed ESM. The chemopreventive effect of thymol against dimethylhydrazine and/or high fat diet-induced colon cancer in rats: relevance to NF-κB. Life Sci. 2021. https://doi.org/10.1016/j.lfs.2021.119335 .
doi: 10.1016/j.lfs.2021.119335
pubmed: 34051216
Aghamohammadi A, Hosseinimehr SJ, Ghasemi A, Azadbakht M, Pourfallah TA. Radiosensitization effects of a Zataria multiflora extract on human glioblastoma cells. Asian Pac J Cancer Prev. 2015;16:7285–90. https://doi.org/10.7314/APJCP.2015.16.16.7285 .
doi: 10.7314/APJCP.2015.16.16.7285
pubmed: 26514525
Lee KP, Kim JE, Park WH, Hong H. Regulation of C6 glioma cell migration by thymol. Oncol Lett. 2016;11:2619–24. https://doi.org/10.3892/ol.2016.4237 .
doi: 10.3892/ol.2016.4237
pubmed: 27073528
pmcid: 4812168
Qoorchi Moheb Seraj F, Heravi-Faz N, Soltani A, Ahmadi SS, Shahbeiki F, Talebpour A, et al. Thymol has anticancer effects in U-87 human malignant glioblastoma cells. Mol Biol Rep. 2022;49:9623–32. https://doi.org/10.1007/s11033-022-07867-3 .
doi: 10.1007/s11033-022-07867-3
pubmed: 35997850
Özgen Ö, Özen Eroğlu G, Küçükhüseyin Ö, Akdeniz N, Hepokur C, Kuruca S, et al. Vitamin D increases the efficacy of cisplatin on bladder cancer cell lines. Mol Biol Rep. 2023. https://doi.org/10.1007/s11033-022-08044-2 .
doi: 10.1007/s11033-022-08044-2
pubmed: 36370297
Arzumanian VA, Kiseleva OI, Poverennaya EV. The curious case of the HepG2 cell line: 40 years of expertise. Int J Mol Sci. 2021. https://doi.org/10.3390/ijms222313135 .
doi: 10.3390/ijms222313135
pubmed: 34884942
pmcid: 8658661
Sharifi-Rad J, Sharifi-Rad M, Hoseini-Alfatemi SM, Iriti M, Sharifi-Rad M, Sharifi-Rad M. Composition, cytotoxic and antimicrobial activities of Satureja intermedia C.A. Mey essential oil. Int J Mol Sci. 2015;16:17812–25. https://doi.org/10.3390/ijms160817812 .
doi: 10.3390/ijms160817812
pubmed: 26247936
pmcid: 4581223
Fitsiou E, Anestopoulos I, Chlichlia K, Galanis A, Kourkoutas I, Panayiotidis MI, et al. Antioxidant and antiproliferative properties of the essential oils of Satureja thymbra and Satureja parnassica and their major constituents. Anticancer Res. 2016;36:5757–63. https://doi.org/10.21873/anticanres.11159 .
doi: 10.21873/anticanres.11159
pubmed: 27793897
Ferraz RPC, Bomfim DS, Carvalho NC, Soares MBP, Da Silva TB, Machado WJ, et al. Cytotoxic effect of leaf essential oil of Lippia gracilis Schauer (Verbenaceae). Phytomedicine. 2013;20:615–21.
doi: 10.1016/j.phymed.2013.01.015
pubmed: 23453306
Kavak E, Mutlu D, Ozok O, Arslan S, Kivrak A. Design, synthesis and pharmacological evaluation of novel Artemisinin-Thymol. Nat Prod Res. 2020. https://doi.org/10.1080/14786419.2020.1865954 .
doi: 10.1080/14786419.2020.1865954
Lv R, Chen Z. Thymol inhibits cell migration and invasion by downregulating the activation of PI3K/AKT and ERK pathways in human colon cancer cells. Trop J Pharm Res. 2018;16:2895–901. https://doi.org/10.4314/tjpr.v16i12.13 .
doi: 10.4314/tjpr.v16i12.13
Elshafie HS, Armentano MF, Carmosino M, Bufo SA, De Feo V, Camele I. Cytotoxic activity of Origanum vulgare L. on hepatocellular carcinoma cell line HepG2 and evaluation of its biological activity. Molecules. 2017;22:1435. https://doi.org/10.3390/molecules22091435 .
doi: 10.3390/molecules22091435
pubmed: 28867805
pmcid: 6151800
Ozkan A, Erdogan A. A comparative study of the antioxidant/prooxidant effects of carvacrol and thymol at various concentrations on membrane and DNA of parental and drug resistant H1299 cells. Nat Prod Commun. 2012;7:1557–60. https://doi.org/10.1177/1934578X1200701201 .
doi: 10.1177/1934578X1200701201
pubmed: 23413548
Palabiyik SS, Karakus E, Halici Z, Cadirci E, Bayir Y, Ayaz G, et al. The protective effects of carvacrol and thymol against paracetamol-induced toxicity on human hepatocellular carcinoma cell lines (HepG2). Hum Exp Toxicol. 2016;35:1252–63. https://doi.org/10.1177/0960327115627688 .
doi: 10.1177/0960327115627688
pubmed: 26801986
Shettigar NB, Das S, Rao NB, Rao SBS. Thymol, a monoterpene phenolic derivative of cymene, abrogates mercury-induced oxidative stress resultant cytotoxicity and genotoxicity in hepatocarcinoma cells. Environ Toxicol. 2015;30:968–80. https://doi.org/10.1002/tox.21971 .
doi: 10.1002/tox.21971
pubmed: 24574037
Kaloni D, Diepstraten ST, Strasser A, Kelly GL. BCL-2 protein family: attractive targets for cancer therapy. Apoptosis. 2023;28:20–38. https://doi.org/10.1007/s10495-022-01780-7 .
doi: 10.1007/s10495-022-01780-7
pubmed: 36342579
Raji-Amirhasani A, Khaksari M, Soltani Z, Saberi S, Iranpour M, Darvishzadeh Mahani F, et al. Beneficial effects of time and energy restriction diets on the development of experimental acute kidney injury in rat: Bax/Bcl-2 and histopathological evaluation. BMC Nephrol. 2023;24:59. https://doi.org/10.1186/s12882-023-03104-6 .
doi: 10.1186/s12882-023-03104-6
pubmed: 36941590
pmcid: 10026443
Salakou S, Kardamakis D, Tsamandas A, Zolota V, Apostolakis E, Tzelepi V, et al. Increased Bax/Bcl-2 ratio up-regulates caspase-3 and increases apoptosis in the thymus of patients with myasthenia gravis. In Vivo (Brooklyn). 2007;21:123–32.
Zhu L, Han MB, Gao Y, Wang H, Dai L, Wen Y, et al. Curcumin triggers apoptosis via upregulation of Bax/Bcl-2 ratio and caspase activation in SW872 human adipocytes. Mol Med Rep. 2015;12:1151–6. https://doi.org/10.3892/mmr.2015.3450 .
doi: 10.3892/mmr.2015.3450
pubmed: 25760477
Roos WP, Kaina B. DNA damage-induced cell death: from specific DNA lesions to the DNA damage response and apoptosis. Cancer Lett. 2013;332:237–48.
doi: 10.1016/j.canlet.2012.01.007
pubmed: 22261329
Sancar A, Lindsey-Boltz LA, Ünsal-Kaçmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Ann Rev Biochem. 2004;73:39–85. https://doi.org/10.1146/annurev.biochem.73.011303.073723 .
doi: 10.1146/annurev.biochem.73.011303.073723
pubmed: 15189136
Roos WP, Kaina B. DNA damage-induced cell death by apoptosis. Trends Mol Med. 2006;12:440–50.
doi: 10.1016/j.molmed.2006.07.007
pubmed: 16899408
Shekh R, Tiwari RK, Ahmad A, Ahmad I, Alabdallah NM, Saeed M, et al. Ethanolic extract of Coleus aromaticus leaves impedes the proliferation and instigates apoptotic cell death in liver cancer HepG2 cells through repressing JAK/STAT cascade. J Food Biochem. 2022. https://doi.org/10.1111/jfbc.14368 .
doi: 10.1111/jfbc.14368
pubmed: 35945689