Anti-Cancer Study of Carvacrol in Hypoxic-Induced Colorectal Cancer Cell
Aumaima Tariq Abed 1,2* , Ahmed MH AlMudhafar 1 , and Najah R Hadi 1
Journal of Angiotherapy 8(1) 1-6 https://doi.org/10.25163/angiotherapy.819441
Submitted: 18 December 2023 Revised: 21 January 2024 Published: 22 January 2024
Effect of carvacrol on proliferation and migration of hypoxic SW480 cancer cells
Abstract
Introduction: Colorectal cancer presents a complex global health challenge, characterized by complications arising from metastasis development due to rapid proliferation, adaptation to hypoxia, and angiogenesis. Carvacrol, a natural monoterpenoid phenol derived from various plants, has interest for its diverse pharmacological properties, particularly its antitumor effects. Methods: We aimed to assess the inhibitory effect of carvacrol on cell migration and proliferation in the hypoxic colorectal cancer cell line (SW480). Chemical induction of hypoxia using cobalt chloride and serially diluted concentrations of carvacrol (400, 200, 100, 50, 25, and 12.5 µg/ml) were employed to evaluate the cytotoxic effect via the MTT assay. Smaller concentrations (low IC50) were used to examine the impact of carvacrol on SW480 cell migration through a cell migration assay (50, 25, 12.5, and 6.25 µg/ml). Results: The results demonstrated a significant, dose-dependent reduction in both cell proliferation and migration with carvacrol doses. Conclusion: The findings suggest that carvacrol could be useful as an adjuvant therapy and a promising addition for patients with highly metastatic colorectal cancer.
Keywords: Carvacrol, hypoxia, colorectal, SW480, proliferation, migration.
References
Abid, AT.; Al-Kafaji B.; Karbel H. and Naji H. (2014). Damper Effect of Carvacrol on T47-D, A Human Breast Cancer Cell Line. Medical Journal of Babylon-Vol. 11- No. 4 -2014
Aligiannis N, Kalpoutzakis E, Mitaku S, Chinou IB (2001) Composition and antimicrobial activity of the essential oils of two Origanum species. J Agric Food Chem 49:4168–4170
American Cancer Society. Cancer Facts and Figures 2011. Available from: http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/ documents/document/acspc-029771.pdf. Accessed November 18, 2011.
Bhandari, V. et al. (2019). Molecular landmarks of tumor hypoxia across cancer types. Nat. Genet. 51, 308–318 (2019).
Bnyan, IA.; Abid AT. and Obied HN. (2014). Antibacterial Activity of Carvacrol against Different Types of Bacteria. Journal of Natural Sciences Research. 4(9): 13-16.
Can Baser K. (2008). Biological and pharmacological activities of carvacrol and carvacrol bearing essential oils. Curr Pharm Des 14:3106–3119
Canning MT, Postovit LM, Clarke SH, Graham CH. (2001). Oxygen-mediated regulation of gelatinase and tissue inhibitor of metalloproteinases-1 expression by invasive cells. Exp Cell Res 267, 88-94
Casillas, A. L. et al. (2018). Hypoxia-inducible PIM kinase expression promotes resistance to antiangiogenic agents. Clin. Cancer Res. 24, 169–180 (2018).
Corina, D., Florina, B., Iulia, P., Cristina, D., Rita, A., Alexandra, P., … Codruta, S. (2017). Rutin and Its Cyclodextrin Inclusion Complexes: Physico- chemical Evaluation and in vitro Activity on B164A5 Murine Melanoma Cell Line. Current Pharmaceutical Biotechnology, 18, 1067–1077.
Dai, Z. J. et al. (2012). Up-regulation of hypoxia inducible factor-1alpha by cobalt chloride correlates with proliferation and apoptosis in PC-2 cells. J. Exp. Clin. Cancer Res. 31, 1756–9966 (2012).
Danli Wu and Yotnda P. (2011). Induction and Testing of Hypoxia in Cell Culture. Journal of Visualized Experiment. August 2011, 54, e2899, 1- 4.
Di Mattia M, Mauro A, Monache SD, Pulcini F, Russo V, Berardinelli P, Citeroni MR, Turriani M, Peserico A and Barboni B. (2022). Hypoxia-Mimetic CoCl2 Agent Enhances Pro-Angiogenic Activities in Ovine Amniotic Epithelial Cells-Derived Conditioned Medium. Cells 2022, 11, 461.
Fatima K, Luqman S and Meena A. (2022). Carvacrol Arrests the Proliferation of Hypopharyngeal Carcinoma Cells by Suppressing Ornithine Decarboxylase and Hyaluronidase Activities. Frontiers in Nutrition. April 2022. Volume 9.
Fenaroli G. Fenaroli’s Handbook of Flavor Ingredients. Lincoln: Taylor and Francis (1975)
Hadian J, Esmaeili H, Nadjafi F, Khadivi-Khub A. (2014). Essential oil characterization of Saturejarechingeri in Iran. Ind Crops Prod. (2014) 61:403–9. doi: 10.1016/j.indcrop.2014.07.034
Hurwitz H, Fehrenbacher L, Novotny W, et al. (2004). Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335–42.
Islami F, Goding Sauer A, Miller KD, et al. (2017). Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J Clin., 68, 31-54
Jin MZ, Jin WL. (2020). The Updated Landscape of Tumor Microenvironment and Drug Repurposing. Signal Transduct Target Ther (2020) 5(1):166. doi: 10.1038/s41392-020-00280-x
Khan I., Bhardwaj M., Shruti Shukla S., Lee. H., Oh M., Bajpai VK., Huh YS ., and Kang SC. Carvacrol encapsulated nanocarrier/ nanoemulsion abrogates angiogenesis by downregulating COX-2, VEGF and CD31 in vitro and in vivo in a lung adenocarcinoma model. colloids and Surfaces B: Biointerfaces 181 (2019) 612–622
Lai, K. , Luo, C. , Zhang, X. , Ye, P. , Zhang, Y. , He, J. , & Yao, K. (2016). Regulation of angiogenin expression and epithelial-mesenchymal transition by HIF-1alpha signaling in hypoxic retinal pigment epithelial cells. Biochimica et Biophysica Acta, 1862, 1594–1607. 10.1016/j.bbadis.2016.05.023
Li C, Wang Q, Shen S, Wei X, and Li G. (2019). HIF-1α/VEGF signaling-mediated epithelial–mesenchymal transition and angiogenesis is critically involved in anti- metastasis effect of luteolin in melanoma cells. Phytotherapy Research. 2019;33:798–807.
M. De Vincenzi, A. Stammati, A. De Vincenzi, M. Silano, (2004). Constituents of aromatic plants: carvacrol, Fitoterapia 75 (2004) 801–804.
Maxwell PH, Dachs GU, Gleadle JM, Nicholls LG, Harris AL, Stratford IJ, Hankinson O, Pugh CW, Ratcliffe PJ. (1997). Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci USA. 1997; 94: 8104-8109.
Mezzoug N, Elhadri A, Dallouh A, Amkiss S, Skali NS, Abrini J, et al. (2007). Investigation of the mutagenic and antimutagenic effects of origanumcompactum essential oil and some of its constituents, Mutat. Res Genet Toxicol Environ Mutagen. (2007) 629:100–10. doi: 10.1016/j.mrgentox.2007.01.011
Morbidelli L, Terzuoli E and Donnin S. Use of Nutraceuticals in Angiogenesis-Dependent Disorders. Molecules 2018, 23, 2676; doi:10.3390/molecules23102676.
MSS Khan, AMSA Majid, MA Iqbal, ASA Majid. (2016). Designing the angiogenic inhibitor for brain tumor via disruption of VEGF and IL17A expression, European Journal of Pharmaceutical Sciences, 2016
Munoz-Najar UM, Neurath KM, Vumbaca F, Claffey KP. (2006). Hypoxia stimulates breast carcinoma cell invasion through MT1-MMP and MMP-2 activation. Oncogene 25, 2379-2392
Muz B, De la Puente P, Azab F , Azab A. (2015) The role of hypoxia in cancer progression, angiogenesis, metastasis, and resistance to therapy. Hypoxia 2015:3 83-92.
Ni, C. S. , Sun, B. C. , Dong, X. Y. , Sun, T. , Zhao, N. , Liu, Y. R. , & Gu, Q. (2012). Promoting melanoma growth and metastasis by enhancing VEGF expression. Contemporary Oncology, 16, 526–531. 10.5114/wo.2012.32486
Nostro A, Scaffaro R, D’Arrigo M, Botta L, Filocamo A, Marino A, et al. (2012). Study on carvacrol and cinnamaldehyde polymeric films: mechanical properties, release kinetics and antibacterial and antibiofilm activities. Appl Microbiol Biotechnol. (2012) 96:1029–38. doi: 10.1007/s00253-012-4091-3
Piret JP, Mottet D, Raes M, and Michiels C. (2002). CoCl 2 , a Chemical Inducer of Hypoxia-Inducible Factor-1, and Hypoxia Reduce Apoptotic Cell Death in Hepatoma Cell Line HepG2. Ann.N.Y.Acad.Sci.973:443-447(2002).
Shweiki D, Neeman M, Itin A, Keshet E. (1995). Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumor angiogenesis. Proc Natl Acad Sci USA. 1995; 92: 768-772.
Si, L., Yan, X., Hao, W., Ma, X., Ren, H., Ren, B., et al. (2018). Licochalcone D induces apoptosis and inhibits migration and invasion in human melanoma A375 cells. Oncology Reports, 39, 2160–2170.
Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2019. CA Cancer J. Clin. 69, 7–34
Taddei ML, Giannoni E, Comito G, Chiarugi P. (2013). Microenvironment and Tumor Cell Plasticity: An Easy Way Out. Cancer Lett (2013) 341(1):80–96. doi: 10.1016/j.canlet.2013.01.042
Yang, Y., Gao, M., Lin, Z., Chen, L., Jin, Y., Zhu, G.,et al. (2017). DEK promoted EMT and angiogenesis through regulating PI3K/AKT/mTOR pathway in triple-negative breast cancer. Oncotarget, 8, 98708–98722.
Z.E. Suntres, J. Coccimiglio, M. Alipour, (2015). The bioactivity and toxicological actions of carvacrol, Crit. Rev. Food Sci. Nutr. 55 (2015) 304–318.
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