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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

COX-2 Docking Structural Analysis with Phytochemical Extracts of Rosemary: A Possible Cytotoxicity on Head and Neck Squamous Cell Carcinoma Cell Line (HEp-2)

Author(s): Ihab S. Abd El-Hamid *, Yara Y. Mouselhy, Marwa M. El-Shafei, Marwa M. Sayed, Aly F. Mohamed and Doaa B. Farag

Volume 19 , Issue 12 , 2019

Page: [1473 - 1480] Pages: 8

DOI: 10.2174/1871520619666190618121706

Price: $65


Background: Various phenolic phytochemical extracts have been claimed to exhibit different types of biological activity, including anti-inflammatory, anti-oxidative and anti-carcinogenic activity. Carnosol and carnosic acid, extracts of rosemary, are among these phenolic compounds.

Materials and Methods: CHARMm-based molecular docking was performed to estimate the possible molecular interactions of both carnosic acid and carnosol with the COX-2 active binding site. An MTT assay was used to evaluate HEp-2 cell viability after incubation for 48 hours with low or high concentrations of carnosol, carnosic acid or their combination. The levels of COX-2 were measured in cell lysate by the quantitative indirect ELISA technique.

Results: Docking revealed favourable negative binding energies as well as binding interactions of both carnosic acid and carnosol within the binding site of the COX-2 receptor. Carnosic acid showed more favourable binding potential than carnosol. One-way ANOVA and Bonferroni’s post hoc tests revealed significant differences in cytotoxicity among cells treated with different concentrations of the rosemary extracts (P< 0.001). ELISA revealed significant reductions in COX-2 protein levels in HEp-2 cells treated with either carnosic acid (-1.42- fold) or carnosol (-3.16-fold) compared to control cells.

Conclusion: Both rosemary extracts, carnosol and carnosic acid, exert potential cytotoxic effects on the HEp-2 cell line via inhibition of the COX-2 pathway. The combination of carnosol and carnosic acid exerts a stronger cytotoxic effect than either compound alone.

Keywords: Rosemary, carnosic acid, carnosol, COX-2, docking, HEp-2.

Graphical Abstract
Jemal, A.; Bray, F.; Center, M.; Ferlay, J.; Ward, E.; Forman, D. Global cancer statistics. CA Cancer J. Clin., 2011, 61, 69-90.
Ferlay, J.; Shin, H.R.; Bray, F.; Forman, D.; Mathers, C.; Parkin, D.M. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int. J. Cancer, 2010, 127, 2893-2917.
Ferlay, J.; Soerjomataram, I.; Dikshit, R.; Eser, S.; Mathers, C.; Rebelo, M.; Parkin, D.M.; Forman, D.; Bray, F. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer, 2015, 136, 359-386.
Tsai, C.W.; Lin, C.Y.; Lin, H.H.; Chen, J.H. Carnosic acid, a rosemary phenolic compound, induces apoptosis through reactive oxygen species-mediated p38 activation in human neuroblastoma IMR-32 cells. Neurochem. Res., 2011, 36, 2442-2451.
Ngo, S.N.; Williams, D.B.; Head, R.J. Rosemary and cancer prevention: Preclinical perspectives. Crit. Rev. Food Sci. Nutr., 2011, 51, 946-954.
Altinier, G.; Sosa, S.; Aquino, R.P.; Mencherini, T.; Della-Loggia, R.; Tubaro, A. Characterization of topical anti-inflammatory compounds in Rosmarinus officinalis L. J. Agric. Food Chem., 2007, 55, 1718-1723.
Pérez-Fons, L.; Garzón, M.T.; Micol, V. Relationship between the antioxidant capacity and effect of rosemary (Rosmarinus officinalis L.) polyphenols on membrane phospholipid order. J. Agric. Food Chem., 2010, 58, 161-171.
Park, K.W.; Kundu, J.; Chae, I.G.; Kim, D.H.; Yu, M.H.; Kundu, J.K.; Chun, K.S. Carnosol induces apoptosis through generation of ROS and inactivation of STAT3 signaling in human colon cancer HCT116 cells. Int. J. Oncol., 2014, 44, 1309-1315.
Borrás-Linares, I.; Stojanović, Z.; Quirantes-Piné, R.; Arráez-Román, D.; Švarc-Gajić, J.; Fernández-Gutiérrez, A.; Segura-Carretero, A. Rosmarinus officinalis leaves as a natural source of bioactive compounds. Int. J. Mol. Sci., 2014, 15, 20585-20606.
Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100, 57-70.
Green, D.R.; Victor, B. The pantheon of the fallen: Why are there so many forms of cell death? Trends Cell Biol., 2012, 22, 555-556.
Fritsche, E.; Baek, S.J.; King, L.M.; Zeldin, D.C.; Eling, T.E.; Bell, D.A. Functional characterization of cyclooxygenase-2 polymorphisms. J. Pharmacol. Exp. Ther., 2001, 299, 468-476.
Krysan, K.; Dalwadi, H.; Sharma, S.; Pold, M.; Dubinett, S. Cyclooxygenase 2-dependent expression of survivin is critical for apoptosis resistance in non-small cell lung cancer. Cancer Res., 2004, 64, 6359-6362.
Visanji, J.M.; Thompson, D.G.; Padfield, P.J. Induction of G2/M phase cell cycle arrest by Carnosol and Carnosic acid is associated with alteration of cyclin A and cyclin B1 levels. Cancer Lett., 2006, 237, 130-136.
Tai, J.; Cheung, S.; Wu, M.; Hasman, D. Antiproliferation effect of Rosemary (Rosmarinus officinalis) on human ovarian cancer cells in vitro. Phytomedicine, 2012, 19, 436-443.
Yesil-Celiktas, O.; Sevimli, C.; Bedir, E.; Vardar-Sukan, F. Inhibitory effect of rosemary extracts, Carnosic acid and rosemarinic acid on the growth of various human cancer cell lines. Plant Foods Hum. Nutr., 2010, 65, 158-163.
Lopez-Jimenez, A.; Carcia-Caballero, M.; Medina, M.A.; Quesada, A.R. Anti-angiogenic properties of Carnosol and Carnosic acid, two major dietary compounds from rosmary. Eur. J. Nutr., 2013, 52, 85-95.
Kar, S.; Palit, S.; Ball, W.B.; Das, P.K. Carnosic acid modulates Akt/IKK/NF-kappaB signaling by PP2A and induces intrinsic and extrinsic pathway mediated apoptosis in human prostate carcinoma PC-3 cells. Apoptosis, 2012, 17, 735-747.
Dörrie, J.; Sapala, K.; Zunino, S.J. Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia cells. Cancer Lett., 2001, 170, 33-39.
González-Vallinas, M.; Molina, S.; Vicente, G.; Zarza, V.; Martín-Hernández, R.; García-Risco, M.R.; Fornari, T.; Reglero, G.; Ramírez de Molina, A. Expression of MicroRNA-15b and the glycosyltransferase GCNT3 correlates with antitumor efficacy of rosemary diterpenes in colon and pancreatic cancer. PLoS One, 2014, 9e98556
Yildiz-Ozturk, E.; Gulce-Iz, S.; Anil, M.; Yesil-Celiktas, O. Cytotoxic responses of Carnosic acid and doxorubicin on breast cancer cells in butterfly-shaped microchips in comparison to 2D and 3D culture. Cytotechnology, 2017, 69, 337-347.

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