Assessment of Rutin's Anti-Metastatic Potential: Targeting the CXCL8/CXCR2 Chemokine Signaling Pathway in Oral Cancer Cell Line
Abstract:
Rutin is a flavonoid compound that is naturally found in many plant-based foods such as citrus fruits, buckwheat, and apples. It has been studied for its potential anti-cancer effects. The aim of the study is to investigate the anti-cancer effect of Rutin by targeting the CXCL-8/CXCR2 signaling pathway in oral cancer cells. To evaluate the cytotoxic potential of Rutin we have performed an MTT assay. A phase contrast microscope is used to evaluate changes in cell morphology. A scratch wound healing assay was performed to evaluate anti-migrative potential of rutin. Gene expression analysis was performed using quantitative real-time PCR to determine the levels of CXCL-8/CXCR2 signalling molecules. In our study, the exposure of oral cancer cells to rutin led to a notable decrease in cell viability, with a statistically significant difference observed (p < 0.05) between the control and treatment groups. The inhibitory concentration (IC-50) was determined to be 80 μg/ml for oral cancer cells. Post-treatment, a reduced number of cells were observed, exhibiting shrinkage and cytoplasmic membrane blebbing. The investigation indicated a significant downregulation of CXCL-8/CXCR2 mRNA expression following rutin treatment. Additionally, the migration of cells was significantly reduced compared to control cells. The results demonstrated that the Rutin was cytotoxic and inhibited cell migration by targeting the CXCL-8/CXCR2 signaling molecules gene expression in oral cancer cells. However, more research is needed to understand the mechanisms of the anti-cancer potential of this Rutin, by targeting the CXCL-8/CXCR2 signaling pathway might help to treat cancer.
References:
[1]. M. Cordani, M., Á. Somoza, A., M. Tafani, M., I. Dando, I., S. Kumar, S., 2021, Novel Cancer Treatments based on Autophagy Modulation, Frontiers Media SA, https://books.google.com/books/about/Novel_Cancer_Treatments_based_on_Autopha.html?hl=&id=OMwyEAAAQBAJ.
[2]. Y. Li, Y., J. Zhang, J., P. Song, P., X. Miao, X., G. Liu, G., C. Yang, C., X. Wei, X., N. Li, N., F. Bian, F., 2020, Small-Angle X-ray Scattering for PEGylated Liposomal Doxorubicin Drugs: An Analytical Model Comparison Study, Mol. Pharm. 20, 4654–4663. https://doi.org/10.1021/acs.molpharmaceut.3c00396.
[3]. P. K. Mukherjee, P. K., 2022, Evidence-Based Validation of Herbal Medicine: Translational Research on Botanicals, Elsevier, https://play.google.com/store/books/details?id=9RxoEAAAQBAJ.
[4]. N.M. Al-Ekaid, N.M., A. Al-Samydai, A., I. Al-Deeb, I., H. Nsairat, H., K. Khleifat, K., W. Alshaer, W., 2023, Preparation, Characterization, and Anticancer Activity of PEGylated Nano Liposomal Loaded with Rutin against Human Carcinoma Cells (HT-29), Chem. Biodivers. 20, e202301167. https://doi.org/10.1002/cbdv.202301167.
[5]. S. M. Dizaj, S. M., M. Kouhsoltani, M., K. Pourreza, K., S. Sharifi, S., E. D. Abdolahinia, E.D., 2023, Preparation, Characterization, and Evaluation of the Anticancer Effect of Mesoporous Silica Nanoparticles Containing Rutin and Curcumin, Pharm Nanotechnol. https://doi.org/10.2174/2211738511666230818092706.
[6]. M. Ross, M. (Molecular cell biologist), 2018, Bone-induced Expression of Tumoral Integrin [beta]3 Enables Targeted Nanotherapy of Breast Cancer Metastases, https://books.google.com/books/about/Bone_induced_Expression_of_Tumoral_Integ.html?hl=&id=vDm2uQEACAAJ.
[7]. M. Masih, M., S. Agarwal, S., R. Kaur, R., P. K. Gautam, P. K., 2022, Role of chemokines in breast cancer, Cytokine 155, 155909. https://doi.org/10.1016/j.cyto.2022.155909.
[8]. A. Mishra, A., K. H. Suman, K. H., N. Nair, N., J. Majeed, J., V. Tripathi, V., 2021, An updated review on the role of the CXCL8-CXCR1/2 axis in the progression and metastasis of breast cancer, Mol. Biol. Rep. 48, 6551–6561. https://doi.org/10.1007/s11033-021-06648-8.
[9]. A. Birbrair, A., 2021, Tumor Microenvironment: The Role of Chemokines – Part B, Springer Nature, https://play.google.com/store/books/details?id=WXM5EAAAQBAJ.
[10]. K. M. K. Masthan, K. M. K., V. Shyamsundar, V., N. Aravindha Babu, N., 2015, Color Atlas of Oral Cancer, JP Medical Ltd,. https://books.google.com/books/about/Color_Atlas_of_Oral_Cancer.html?hl=&id=VqyfCwAAQBAJ.
[11]. T. Kirita, T., K. Omura, K., 2015, Oral Cancer: Diagnosis and Therapy, Springer, https://play.google.com/store/books/details?id=ZR7OBgAAQBAJ.
[12]. M. He, M., K. Yasin, K., S. Yu, S., J. Li, J., L. Xia, L., 2023, Total Flavonoids in L. and Evaluation of Its Anticancer Activity, Int. J. Mol. Sci. 24 https://doi.org/10.3390/ijms242216348.
[13]. S. Arimoto-Kobayashi, S., X. Zhang, X., Y. Yuhara, Y., T. Kamiya, T., T. Negishi, T., G. Okamoto, G., 2013, Chemopreventive effects of the juice of Vitis coignetiae Pulliat on two-stage mouse skin carcinogenesis, Nutr. Cancer 65, 440–450. https://doi.org/10.1080/01635581.2013.767916.
[14]. Elumalai, P., Gunadharini, D. N., Senthilkumar, K., Banudevi, S., Arunkumar, R., Benson, C. S., Sharmila, G., Arunakaran, J., 2012, Induction of apoptosis in human breast cancer cells by nimbolide through extrinsic and intrinsic pathway, Toxicol. Lett. 215, 131–142. https://doi.org/10.1016/j.toxlet.2012.10.008.
[15]. Elumalai, P., Ezhilarasan, D., Raghunandhakumar, S., 2022, Quercetin Inhibits the Epithelial to Mesenchymal Transition through Suppressing Akt Mediated Nuclear Translocation of β-Catenin in Lung Cancer Cell Line, Nutr. Cancer 74, 1894–1906. https://doi.org/10.1080/01635581.2021.1957487.
[16]. Elumalai, P., Muninathan, N., Megalatha, S. T., Suresh, A., Kumar, K. S., Jhansi, N., Kalaivani, K., Krishnamoorthy, G., 2022, An Insight into Anticancer Effect of Propolis and Its Constituents: A Review of Molecular Mechanisms, Evid. Based. Complement. Alternat. Med., 5901191. https://doi.org/10.1155/2022/5901191.
[17]. Mohammad Mirzapour, M., Farshdousti Hagh, M., Marofi, F., Solali, S., Alaei, A., 2023, Investigating the synergistic potential of TRAIL and SAHA in inducing apoptosis in MOLT-4 cancer cells, Biochem. Biophys. Res. Commun. 676, 13–20. https://doi.org/10.1016/j.bbrc.2023.05.115.
[18]. Zhao, Z., Ma, Y., Lv, J., Maimaiti, N., Zhang, J., Aibibula, M., Gong, Z., Ling, B., 2022, Expression of chemokine CXCL8/9/10/11/13 and its prognostic significance in head and neck cancer, Medicine 101, e29378. https://doi.org/10.1097/MD.0000000000029378.
[19]. Platanias, L. C., 2006, Cytokines and Cancer, Springer Science & Business Media, https://play.google.com/store/books/details?id=2WUPzLlx0x0C.
[20]. Ackerman, L. H., de Mello Souza, C. H., Cortés-Hinojosa, G., Salute, M. E., Stephen, A. A., Anthony, E., Shiomitsu, K., Milner, R. J., 2022, Identification of the interleukin-8 (CXCL-8) pathway in feline oral squamous cell carcinoma - A pilot study, Can. J. Vet. Res. 86, 13–19. https://www.ncbi.nlm.nih.gov/pubmed/34975217.
