Login Register Cart 0
Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

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

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Eugenol Inhibits the Biological Activities of an Oral Squamous Cell Carcinoma Cell Line SCC9 via Targeting MIF

Author(s): Yao Duan, Xiaojin Huang, Bo Qiao, Rui Ma and Jialin Li*

Volume 22, Issue 15, 2022

Published on: 17 May, 2022

Page: [2799 - 2806] Pages: 8

DOI: 10.2174/1871520622666220324105435

Price: $65

conference banner
Abstract

Background: Oral squamous cell carcinoma (OSCC) is a rampant cancer type in head and neck cancers with a poor prognosis and a high recurrence rate. Eugenol shows an anticancer effect in a variety of cancers, but it has been rarely studied in oral squamous cell carcinoma (OSCC).

Objective: The purpose of this study was to explore the role of Eugenol in OSCC and the underlying mechanism.

Methods: After different concentrations of Eugenol (0, 200, 400, and 800 μM) treatment, the viability, proliferation, migration, and invasion of OSCC cell line SCC9 were measured by CCK-8, colony formation, wound-healing, and transwell assays, respectively. TUNEL staining was employed to detect apoptosis. Western blotting was used to evaluate gene expression at the protein level. Molecular docking was used to identify the target of Eugenol.

Results: Eugenol decreased the proliferation and reduced the abilities of invasion and migration along with the expression of matrix metalloproteinases (MMP) 2 and MMP9 in SCC9 cells. On the contrary, the ratio of apoptotic cells was increased by Eugenol. In addition, Eugenol down-regulated B cell lymphoma-2 (Bcl-2) expression, but up-regulated BCL-2 associated X (Bax), cleaved caspase 3, and cleaved poly-ADP ribose polymerase (PARP) expression. Meanwhile, Eugenol exerted its effect on SCC9 cells in a concentration-dependent manner. Eugenol could bind to macrophage migration inhibitory factor (MIF), the expression of which was down-regulated after Eugenol treatment. Besides, overexpression of MIF reversed all the effects of Eugenol on OSCC cells.

Conclusion: In summary, Eugenol suppressed the malignant processes of OSCC cells by targeting MIF, which could guide the clinical application of Eugenol in OSCC.

Keywords: Oral squamous cell carcinoma, eugenol, macrophage migration inhibitory factor, migration, invasion, TUNEL staining.

« Previous
Graphical Abstract

[1]
Peach, M.S.; Trifiletti, D.M.; Vachani, C.; Arnold-Korzeniowski, K.; Bach, C.; Hampshire, M.; Metz, J.M.; Hill-Kayser, C.E. Patient-reported outcomes in head and neck cancer: Prospective multi-institutional patient-reported toxicity. Patient Relat. Outcome Meas., 2018, 9, 245-252.
[http://dx.doi.org/10.2147/PROM.S153919] [PMID: 30100773]
[2]
Chen, Y.; Ding, Y. LINC00467 enhances head and neck squamous cell carcinoma progression and the epithelial-mesenchymal transition process via miR-299-5p/ubiquitin specific protease-48 axis. J. Gene Med., 2020, 22(7), e3184.
[http://dx.doi.org/10.1002/jgm.3184] [PMID: 32159247]
[3]
Wang, N.; Huang, M.; Lv, H. Head and neck verrucous carcinoma: A population-based analysis of incidence, treatment, and prognosis. Medicine (Baltimore), 2020, 99(2), e18660.
[http://dx.doi.org/10.1097/MD.0000000000018660] [PMID: 31914052]
[4]
Qiao, C.Y.; Qiao, T.Y.; Jin, H.; Liu, L.L.; Zheng, M.D.; Wang, Z.L. LncRNA KCNQ1OT1 contributes to the cisplatin resistance of tongue cancer through the KCNQ1OT1/miR-124-3p/TRIM14 axis. Eur. Rev. Med. Pharmacol. Sci., 2020, 24(1), 200-212.
[PMID: 31957833]
[5]
Gao, F.; Han, J.; Wang, Y.; Jia, L.; Luo, W.; Zeng, Y. Circ_0109291 Promotes the cisplatin resistance of oral squamous cell carcinoma by sponging miR-188-3p to increase ABCB1 expression. Cancer Biother. Radiopharm., 2020, cbr.2020.3928.
[http://dx.doi.org/10.1089/cbr.2020.3928] [PMID: 32758011]
[6]
Wang, H.C.; Liu, P.L.; Lo, P.C.; Chang, Y.T.; Chan, L.P.; Yeh, T.J.; Hsiao, H.H.; Cho, S.F. Consistent administration of cetuximab is asso-ciated with favorable outcomes in recurrent/metastatic head and neck squamous cell carcinoma in an endemic carcinogen exposure area: A retrospective observational study. PeerJ, 2020, 8, e9862.
[http://dx.doi.org/10.7717/peerj.9862] [PMID: 32974098]
[7]
Qiu, Y.; Sun, J.; Qiu, J.; Chen, G.; Wang, X.; Mu, Y.; Li, K.; Wang, W. Antitumor activity of cabazitaxel and MSC-TRAIL derived extracel-lular vesicles in drug-resistant oral squamous cell carcinoma. Cancer Manag. Res., 2020, 12, 10809-10820.
[http://dx.doi.org/10.2147/CMAR.S277324] [PMID: 33149686]
[8]
Maurya, S.; Chandra, M.; Yadav, R.K.; Narnoliya, L.K.; Sangwan, R.S.; Bansal, S.; Sandhu, P.; Singh, U.; Kumar, D.; Sangwan, N.S. Inter-species comparative features of trichomes in Ocimum reveal insights for biosynthesis of specialized essential oil metabolites. Protoplasma, 2019, 256(4), 893-907.
[http://dx.doi.org/10.1007/s00709-018-01338-y] [PMID: 30656458]
[9]
Huang, M.Z.; Yang, Y.J.; Liu, X.W.; Qin, Z.; Li, J.Y. Aspirin eugenol ester attenuates oxidative injury of vascular endothelial cells by regulating NOS and Nrf2 signalling pathways. Br. J. Pharmacol., 2019, 176(7), 906-918.
[http://dx.doi.org/10.1111/bph.14592] [PMID: 30706438]
[10]
Taher, Y.A.; Samud, A.M.; El-Taher, F.E.; Ben-Hussin, G.; Elmezogi, J.S.; Al-Mehdawi, B.F.; Salem, H.A. Experimental evaluation of anti-inflammatory, antinociceptive and antipyretic activities of clove oil in mice. Libyan J. Med., 2015, 10(1), 28685.
[http://dx.doi.org/10.3402/ljm.v10.28685] [PMID: 28349790]
[11]
Hwang, S.M.; Lee, K.; Im, S.T.; Go, E.J.; Kim, Y.H.; Park, C.K. Co-application of eugenol and QX-314 elicits the prolonged blockade of voltage-gated sodium channels in nociceptive trigeminal ganglion neurons. Biomolecules, 2020, 10(11), E1513.
[http://dx.doi.org/10.3390/biom10111513] [PMID: 33167484]
[12]
Cui, Z.; Liu, Z.; Zeng, J.; Chen, L.; Wu, Q.; Mo, J.; Zhang, G.; Song, L.; Xu, W.; Zhang, S.; Guo, X. Eugenol inhibits non-small cell lung cancer by repressing expression of NF-κB-regulated TRIM59. Phytother. Res., 2019, 33(5), 1562-1569.
[http://dx.doi.org/10.1002/ptr.6352] [PMID: 30932261]
[13]
Fathy, M.; Fawzy, M.A.; Hintzsche, H.; Nikaido, T.; Dandekar, T.; Othman, E.M. Eugenol exerts apoptotic effect and modulates the sensi-tivity of hela cells to cisplatin and radiation. Molecules, 2019, 24(21), E3979.
[http://dx.doi.org/10.3390/molecules24213979] [PMID: 31684176]
[14]
Kumar, N.; Yadav, N.; Amarnath, N.; Sharma, V.; Shukla, S.; Srivastava, A.; Prasad, P.; Kumar, A.; Garg, S.; Singh, S.; Sehrawat, S.; Lochab, B. Integrative natural medicine inspired graphene nanovehicle-benzoxazine derivatives as potent therapy for cancer. Mol. Cell. Biochem., 2019, 454(1-2), 123-138.
[http://dx.doi.org/10.1007/s11010-018-3458-x] [PMID: 30390174]
[15]
Salah, A.; Bouaziz, C.; Amara, I.; Abid-Essefi, S.; Bacha, H. Eugenol protects against citrinin-induced cytotoxicity and oxidative damages in cultured human colorectal HCT116 cells. Environ. Sci. Pollut. Res. Int., 2019, 26(30), 31374-31383.
[http://dx.doi.org/10.1007/s11356-019-06212-9] [PMID: 31473926]
[16]
Sarkar, A.; Das, S.; Rahaman, A.; Das Talukdar, A.; Bhattacharjee, S.; Mandal, D.P. Eugenol and capsaicin exhibit anti-metastatic activity via modulating TGF-β signaling in gastric carcinoma. Food Funct., 2020, 11(10), 9020-9034.
[http://dx.doi.org/10.1039/D0FO00887G] [PMID: 33016967]
[17]
Kang, Y.; Zhang, Y.; Sun, Y. Macrophage migration inhibitory factor is a novel prognostic marker for human oral squamous cell carcino-ma. Pathol. Res. Pract., 2018, 214(8), 1192-1198.
[http://dx.doi.org/10.1016/j.prp.2018.06.020] [PMID: 30041958]
[18]
Ghosh, R.; Ganapathy, M.; Alworth, W.L.; Chan, D.C.; Kumar, A.P. Combination of 2-methoxyestradiol (2-ME2) and eugenol for apopto-sis induction synergistically in androgen independent prostate cancer cells. J. Steroid Biochem. Mol. Biol., 2009, 113(1-2), 25-35.
[http://dx.doi.org/10.1016/j.jsbmb.2008.11.002] [PMID: 19084597]
[19]
Al-Sharif, I.; Remmal, A.; Aboussekhra, A. Eugenol triggers apoptosis in breast cancer cells through E2F1/survivin down-regulation. BMC Cancer, 2013, 13(1), 600.
[http://dx.doi.org/10.1186/1471-2407-13-600] [PMID: 24330704]
[20]
Júnior, P.L.; Câmara, D.A.; Costa, A.S.; Ruiz, J.L.; Levy, D.; Azevedo, R.A.; Pasqualoto, K.F.; de Oliveira, C.F.; de Melo, T.C.; Pessoa, N.D.; Fonseca, P.M.; Pereira, A.; Araldi, R.P.; Ferreira, A.K. Apoptotic effect of eugenol envolves G2/M phase abrogation accompanied by mitochondrial damage and clastogenic effect on cancer cell in vitro. Phytomedicine, 2016, 23(7), 725-735.
[http://dx.doi.org/10.1016/j.phymed.2016.03.014] [PMID: 27235711]
[21]
Sun, Y.; Ji, B.; Feng, Y.; Zhang, Y.; Ji, D.; Zhu, C.; Wang, S.; Zhang, C.; Zhang, D.; Sun, Y. TRIM59 facilitates the proliferation of colorec-tal cancer and promotes metastasis via the PI3K/AKT pathway. Oncol. Rep., 2017, 38(1), 43-52.
[http://dx.doi.org/10.3892/or.2017.5654] [PMID: 28534983]
[22]
Bloom, B.R.; Bennett, B. Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science, 1966, 153(3731), 80-82.
[http://dx.doi.org/10.1126/science.153.3731.80] [PMID: 5938421]
[23]
Nobre, C.C.; de Araújo, J.M.; Fernandes, T.A.; Cobucci, R.N.; Lanza, D.C.; Andrade, V.S.; Fernandes, J.V. Macrophage Migration Inhibi-tory Factor (MIF): Biological activities and relation with cancer. POR, 2017, 23(2), 235-244.
[http://dx.doi.org/10.1007/s12253-016-0138-6] [PMID: 27771887]
[24]
Richard, V.; Kindt, N.; Saussez, S. Macrophage migration inhibitory factor involvement in breast cancer. (Review) Int. J. Oncol., 2015, 47(5), 1627-1633.
[http://dx.doi.org/10.3892/ijo.2015.3185] [PMID: 26412712]
[25]
Gordon-Weeks, A.N.; Lim, S.Y.; Yuzhalin, A.E.; Jones, K.; Muschel, R. Macrophage migration inhibitory factor: A key cytokine and ther-apeutic target in colon cancer. Cytokine Growth Factor Rev., 2015, 26(4), 451-461.
[http://dx.doi.org/10.1016/j.cytogfr.2015.03.002] [PMID: 25882738]
[26]
Shao, C.; Hedberg, C.; Qian, Y. In vivo imaging of the macrophage migration inhibitory factor in liver cancer with an activity-based probe. Anal. Chem., 2021, 93(4), 2152-2159.
[http://dx.doi.org/10.1021/acs.analchem.0c03964] [PMID: 33406831]
[27]
Zhang, H.; Duan, J.; Wu, O. The expression of macrophage migration inhibitory factor in the non-small cell lung cancer. Saudi J. Biol. Sci., 2020, 27(6), 1527-1532.
[http://dx.doi.org/10.1016/j.sjbs.2020.04.027] [PMID: 32489290]
[28]
França, CM; Batista, AC; Borra, RC Macrophage migration inhibitory factor and oral cancer. J. Oral Pathol. Med., 2013, 42(5), 368-373.
[http://dx.doi.org/10.1111/jop.12011]
[29]
Wang, S.S.; Zheng, M.; Pang, X.; Zhang, M.; Yu, X.H.; Wu, J.B.; Gao, X.L.; Wu, J.S.; Yang, X.; Tang, Y.J.; Tang, Y.L.; Liang, X.H. Mac-rophage migration inhibitory factor promotes the invasion and metastasis of oral squamous cell carcinoma through matrix metalloprotein-2/9. Mol. Carcinog., 2019, 58(10), 1809-1821.
[http://dx.doi.org/10.1002/mc.23067] [PMID: 31219646]
[30]
Li, J.; Zhang, J.; Xie, F.; Peng, J.; Wu, X. Macrophage migration inhibitory factor promotes Warburg effect via activation of the NF-κB/HIF-1α pathway in lung cancer. Int. J. Mol. Med., 2018, 41(2), 1062-1068.
[PMID: 29207023]
[31]
De, R.; Sarkar, S.; Mazumder, S.; Debsharma, S.; Siddiqui, A.A.; Saha, S.J.; Banerjee, C.; Nag, S.; Saha, D.; Pramanik, S.; Bandyopadhyay, U. Macrophage migration inhibitory factor regulates mitochondrial dynamics and cell growth of human cancer cell lines through CD74-NF-κB signaling. J. Biol. Chem., 2018, 293(51), 19740-19760.
[http://dx.doi.org/10.1074/jbc.RA118.003935] [PMID: 30366984]

Rights & Permissions Print Cite
Article Metrics
21
1
© 2024 Bentham Science Publishers | Privacy Policy