Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells
Abstract
:1. Introduction
2. Results
2.1. PD-L1 Expression in Oral Cancer Cells
2.2. Up-Regulation of PD-L1 Expression by IFN-γ in Oral Cancer Cells
2.3. Enhancement of Phosphorylated STAT1 and STAT3 Levels by IFN-γ
2.4. Suppression of the Viability of Oral Cancer Cells by Hesperidin
2.5. Inhibition of Colony-Forming Capacity and Migration of Oral Cancer Cells by Hesperidin
2.6. Inhibitory Effect of Hesperidin on IFN-γ-Induced PD-L1 Protein Expression in Oral Cancer Cells
2.7. Inhibition of IFN-γ-Induced Phosphorylated STAT1 and STAT3 Levels by Hesperidin
3. Discussion
4. Materials and Methods
4.1. Chemical Reagents and Antibodies
4.2. Oral Cancer Cell Lines and Cell Cultures
4.3. Cytotoxic Assay
4.4. Colony Formation Assay
4.5. Immunofluorescence
4.6. Immunoblotting
4.7. Wound Healing Assay
4.8. Invasion Assay
4.9. Statistical Analysis
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Sample Availability
References
- Bayat Mokhtari, R.; Homayouni, T.S.; Baluch, N.; Morgatskaya, E.; Kumar, S.; Das, B.; Yeger, H. Combination therapy in combating cancer. Oncotarget 2017, 8, 38022–38043. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gharat, S.A.; Momin, M.; Bhavsar, C. Oral Squamous Cell Carcinoma: Current Treatment Strategies and Nanotechnology-Based Approaches for Prevention and Therapy. Crit. Rev. Ther. Drug Carrier. Syst. 2016, 33, 363–400. [Google Scholar] [CrossRef] [PubMed]
- Chaturvedi, P.; Vaishampayan, S.S.; Nair, S.; Nair, D.; Agarwal, J.P.; Kane, S.V.; Pawar, P.; Datta, S. Oral squamous cell carcinoma arising in background of oral submucous fibrosis: A clinicopathologically distinct disease. Head Neck 2013, 35, 1404–1409. [Google Scholar] [CrossRef] [PubMed]
- Chaturvedi, A.K.; Graubard, B.I.; Broutian, T.; Pickard, R.K.L.; Tong, Z.Y.; Xiao, W.; Kahle, L.; Gillison, M.L. Effect of Prophylactic Human Papillomavirus (HPV) Vaccination on Oral HPV Infections Among Young Adults in the United States. J. Clin. Oncol. 2018, 36, 262–267. [Google Scholar] [CrossRef] [PubMed]
- Takes, R.P.; Rinaldo, A.; Silver, C.E.; Haigentz, M., Jr.; Woolgar, J.A.; Triantafyllou, A.; Mondin, V.; Paccagnella, D.; de Bree, R.; Shaha, A.R.; et al. Distant metastases from head and neck squamous cell carcinoma. Part, I. Basic aspects. Oral Oncol. 2012, 48, 775–779. [Google Scholar] [CrossRef]
- Le Campion, A.; Ribeiro, C.M.B.; Luiz, R.R.; da Silva Junior, F.F.; Barros, H.C.S.; Dos Santos, K.C.B.; Ferreira, S.J.; Goncalves, L.S.; Ferreira, S.M.S. Low Survival Rates of Oral and Oropharyngeal Squamous Cell Carcinoma. Int. J. Dent. 2017, 2017, 5815493. [Google Scholar] [CrossRef]
- Schoenborn, J.R.; Wilson, C.B. Regulation of interferon-gamma during innate and adaptive immune responses. Adv. Immunol. 2007, 96, 41–101. [Google Scholar] [CrossRef]
- Cerezo, M.; Guemiri, R.; Druillennec, S.; Girault, I.; Malka-Mahieu, H.; Shen, S.; Allard, D.; Martineau, S.; Welsch, C.; Agoussi, S.; et al. Translational control of tumor immune escape via the eIF4F-STAT1-PD-L1 axis in melanoma. Nat. Med. 2018, 24, 1877–1886. [Google Scholar] [CrossRef]
- Qing, Y.; Stark, G.R. Alternative activation of STAT1 and STAT3 in response to interferon-gamma. J. Biol. Chem. 2004, 279, 41679–41685. [Google Scholar] [CrossRef] [Green Version]
- Chen, J.; Feng, Y.; Lu, L.; Wang, H.; Dai, L.; Li, Y.; Zhang, P. Interferon-gamma-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway. Immunobiology 2012, 217, 385–393. [Google Scholar] [CrossRef]
- Soliman, H.; Khalil, F.; Antonia, S. PD-L1 expression is increased in a subset of basal type breast cancer cells. PLoS ONE 2014, 9, e88557. [Google Scholar] [CrossRef] [Green Version]
- Homma, S.; Hayashi, K.; Yoshida, K.; Sagawa, Y.; Kamata, Y.; Ito, M. Nafamostat mesilate, a serine protease inhibitor, suppresses interferon-gamma-induced up-regulation of programmed cell death ligand 1 in human cancer cells. Int. Immunopharmacol. 2018, 54, 39–45. [Google Scholar] [CrossRef] [PubMed]
- Garcia-Diaz, A.; Shin, D.S.; Moreno, B.H.; Saco, J.; Escuin-Ordinas, H.; Rodriguez, G.A.; Zaretsky, J.M.; Sun, L.; Hugo, W.; Wang, X.; et al. Interferon Receptor Signaling Pathways Regulating PD-L1 and PD-L2 Expression. Cell. Rep. 2017, 19, 1189–1201. [Google Scholar] [CrossRef] [Green Version]
- Hamid, O.; Robert, C.; Daud, A.; Hodi, F.S.; Hwu, W.J.; Kefford, R.; Wolchok, J.D.; Hersey, P.; Joseph, R.W.; Weber, J.S.; et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N. Engl. J. Med. 2013, 369, 134–144. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dong, H.; Strome, S.E.; Salomao, D.R.; Tamura, H.; Hirano, F.; Flies, D.B.; Roche, P.C.; Lu, J.; Zhu, G.; Tamada, K.; et al. Tumor-associated B7-H1 promotes T-cell apoptosis: A potential mechanism of immune evasion. Nat. Med. 2002, 8, 793–800. [Google Scholar] [CrossRef] [PubMed]
- Zou, W.; Wolchok, J.D.; Chen, L. PD-L1 (B7-H1) and PD-1 pathway blockade for cancer therapy: Mechanisms, response biomarkers, and combinations. Sci. Transl. Med. 2016, 8, 328rv324. [Google Scholar] [CrossRef] [Green Version]
- Justesen, U.; Knuthsen, P.; Leth, T. Quantitative analysis of flavonols, flavones, and flavanones in fruits, vegetables and beverages by high-performance liquid chromatography with photo-diode array and mass spectrometric detection. J. Chromatogr. A 1998, 799, 101–110. [Google Scholar] [CrossRef]
- Banjerdpongchai, R.; Wudtiwai, B.; Khaw-On, P.; Rachakhom, W.; Duangnil, N.; Kongtawelert, P. Hesperidin from Citrus seed induces human hepatocellular carcinoma HepG2 cell apoptosis via both mitochondrial and death receptor pathways. Tumour. Biol. 2016, 37, 227–237. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lee, C.J.; Wilson, L.; Jordan, M.A.; Nguyen, V.; Tang, J.; Smiyun, G. Hesperidin suppressed proliferations of both human breast cancer and androgen-dependent prostate cancer cells. Phytother. Res. PTR 2010, 24 (Suppl. S1), S15–S19. [Google Scholar] [CrossRef] [PubMed]
- Febriansah, R.; Putri, D.D.; Sarmoko; Nurulita, N.A.; Meiyanto, E.; Nugroho, A.E. Hesperidin as a preventive resistance agent in MCF-7 breast cancer cells line resistance to doxorubicin. Asian Pac. J. Trop. Biomed. 2014, 4, 228–233. [Google Scholar] [CrossRef] [Green Version]
- Xia, R.; Sheng, X.; Xu, X.; Yu, C.; Lu, H. Hesperidin induces apoptosis and G0/G1 arrest in human non-small cell lung cancer A549 cells. Int. J. Mol. Med. 2018, 41, 464–472. [Google Scholar] [CrossRef]
- Yeh, M.H.; Kao, S.T.; Hung, C.M.; Liu, C.J.; Lee, K.H.; Yeh, C.C. Hesperidin inhibited acetaldehyde-induced matrix metalloproteinase-9 gene expression in human hepatocellular carcinoma cells. Toxicol. Lett. 2009, 184, 204–210. [Google Scholar] [CrossRef] [PubMed]
- Kongtawelert, P.; Wudtiwai, B.; Shwe, T.H.; Pothacharoen, P.; Phitak, T. Inhibitory Effect of Hesperidin on the Expression of Programmed Death Ligand (PD-L1) in Breast Cancer. Molecules 2020, 25, 252. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Horita, H.; Law, A.; Hong, S.; Middleton, K. Identifying Regulatory Posttranslational Modifications of PD-L1: A Focus on Monoubiquitinaton. Neoplasia 2017, 19, 346–353. [Google Scholar] [CrossRef]
- Polioudaki, H.; Chantziou, A.; Kalyvianaki, K.; Malamos, P.; Notas, G.; Mavroudis, D.; Kampa, M.; Castanas, E.; Theodoropoulos, P.A. Nuclear localization of PD-L1: Artifact or reality? Cell. Oncol. 2019, 42, 237–242. [Google Scholar] [CrossRef]
- Chen, S.; Crabill, G.A.; Pritchard, T.S.; McMiller, T.L.; Wei, P.; Pardoll, D.M.; Pan, F.; Topalian, S.L. Mechanisms regulating PD-L1 expression on tumor and immune cells. J. Immunother. Cancer. 2019, 7, 305. [Google Scholar] [CrossRef]
- Karachaliou, N.; Gonzalez-Cao, M.; Crespo, G.; Drozdowskyj, A.; Aldeguer, E.; Gimenez-Capitan, A.; Teixido, C.; Molina-Vila, M.A.; Viteri, S.; De Los Llanos Gil, M.; et al. Interferon gamma, an important marker of response to immune checkpoint blockade in non-small cell lung cancer and melanoma patients. Ther. Adv. Med. Oncol. 2018, 10, 1758834017749748. [Google Scholar] [CrossRef]
- Jingjing, W.; Wenzheng, G.; Donghua, W.; Guangyu, H.; Aiping, Z.; Wenjuan, W. Deubiquitination and stabilization of programmed cell death ligand 1 by ubiquitin-specific peptidase 9, X-linked in oral squamous cell carcinoma. Cancer. Med. 2018, 7, 4004–4011. [Google Scholar] [CrossRef] [Green Version]
- Lim, S.O.; Li, C.W.; Xia, W.; Cha, J.H.; Chan, L.C.; Wu, Y.; Chang, S.S.; Lin, W.C.; Hsu, J.M.; Hsu, Y.H.; et al. Deubiquitination and Stabilization of PD-L1 by CSN5. Cancer Cell 2016, 30, 925–939. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rawangkan, A.; Wongsirisin, P.; Namiki, K.; Iida, K.; Kobayashi, Y.; Shimizu, Y.; Fujiki, H.; Suganuma, M. Green Tea Catechin Is an Alternative Immune Checkpoint Inhibitor that Inhibits PD-L1 Expression and Lung Tumor Growth. Molecules 2018, 23, 2071. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Voli, F.; Valli, E.; Lerra, L.; Kimpton, K.; Saletta, F.; Giorgi, F.M.; Mercatelli, D.; Rouaen, J.R.C.; Shen, S.; Murray, J.E.; et al. Intratumoral Copper Modulates PD-L1 Expression and Influences Tumor Immune Evasion. Cancer Res. 2020, 80, 4129–4144. [Google Scholar] [CrossRef] [PubMed]
- Yu, W.; Hua, Y.; Qiu, H.; Hao, J.; Zou, K.; Li, Z.; Hu, S.; Guo, P.; Chen, M.; Sui, S.; et al. PD-L1 promotes tumor growth and progression by activating WIP and beta-catenin signaling pathways and predicts poor prognosis in lung cancer. Cell Death Dis 2020, 11, 506. [Google Scholar] [CrossRef] [PubMed]
- Xu, L.; Zhang, Y.; Tian, K.; Chen, X.; Zhang, R.; Mu, X.; Wu, Y.; Wang, D.; Wang, S.; Liu, F.; et al. Apigenin suppresses PD-L1 expression in melanoma and host dendritic cells to elicit synergistic therapeutic effects. J. Exp. Clin. Cancer. Res. 2018, 37, 261. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aggarwal, V.; Tuli, H.S.; Thakral, F.; Singhal, P.; Aggarwal, D.; Srivastava, S.; Pandey, A.; Sak, K.; Varol, M.; Khan, M.A.; et al. Molecular mechanisms of action of hesperidin in cancer: Recent trends and advancements. Exp. Biol Med. 2020, 245, 486–497. [Google Scholar] [CrossRef] [Green Version]
- Easty, D.M.; Easty, G.C.; Carter, R.L.; Monaghan, P.; Butler, L.J. Ten human carcinoma cell lines derived from squamous carcinomas of the head and neck. Br. J. Cancer 1981, 43, 772–785. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- O-Charoenrat, P.; Rhys-Evans, P.; Modjtahedi, H.; Court, W.; Box, G.; Eccles, S. Overexpression of epidermal growth factor receptor in human head and neck squamous carcinoma cell lines correlates with matrix metalloproteinase-9 expression and in vitro invasion. Int. J. Cancer 2000, 86, 307–317. [Google Scholar] [CrossRef]
- Chotjumlong, P.; Khongkhunthian, S.; Ongchai, S.; Reutrakul, V.; Krisanaprakornkit, S. Human beta-defensin-3 up-regulates cyclooxygenase-2 expression and prostaglandin E2 synthesis in human gingival fibroblasts. J. Periodontal. Res. 2010, 45, 464–470. [Google Scholar] [CrossRef] [PubMed]
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Wudtiwai, B.; Makeudom, A.; Krisanaprakornkit, S.; Pothacharoen, P.; Kongtawelert, P. Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells. Molecules 2021, 26, 5345. https://doi.org/10.3390/molecules26175345
Wudtiwai B, Makeudom A, Krisanaprakornkit S, Pothacharoen P, Kongtawelert P. Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells. Molecules. 2021; 26(17):5345. https://doi.org/10.3390/molecules26175345
Chicago/Turabian StyleWudtiwai, Benjawan, Anupong Makeudom, Suttichai Krisanaprakornkit, Peraphan Pothacharoen, and Prachya Kongtawelert. 2021. "Anticancer Activities of Hesperidin via Suppression of Up-Regulated Programmed Death-Ligand 1 Expression in Oral Cancer Cells" Molecules 26, no. 17: 5345. https://doi.org/10.3390/molecules26175345