Bioaktivitas Antikanker dari Quercetin Bertarget Src dalam Terapi Kanker Paru Bukan Sel Kecil

Refa Rahmaddiansyah✉, Sukarsi Rusti, Dessy Arisanty
DOI: https://doi.org/10.25077/mka.v45.i4.p667-679.2022

Abstract

Kanker paru adalah salah satu jenis kanker yang paling umum dengan penyebab utama kematian akibat kanker di seluruh dunia. Kanker paru bukan sel kecil (NSCLC) adalah jenis kanker yang menyumbang sekitar 85% dari semua kejadian kanker paru-paru. Ini juga memiliki prognosis dan pilihan pengobatan yang buruk. Src adalah salah satu target paling efektif yang terkait dengan pengembangannya. Penelitian ini merupakan studi tinjauan pustaka dengan menggunakan data dari penelitian asli berdasarkan studi in vitro dan in vivo. Hasil penelitian menunjukkan bahwa Que menghambat induksi proliferasi dan metastasis sel NSCLC dengan menekan ekspresi Src yang kemudian menghambat jalur pensinyalan Fn14/NF-κB. Quercetin juga mengganggu pensinyalan faktor nuklir kappa B (NF-κB) yang mengatur ekspresi beberapa gen yang terlibat dalam karsinogenesis, peradangan, dan sitoprotektif. Dengan membungkam Src, metastasis kanker paru-paru akan berkurang. Ketika Src dihambat, sel-sel yang dilepaskan mengalami anoikis sehingga terjadi kematian sel dengan kecepatan mekanisme penghambatan. Dengan demikian, dapat disimpulkan bahwa quercetin berperan sebagai antikanker melalui penghambatan proliferasi tumor, metastasis, dan angiogenesis melalui jalur pensinyalannya pada sel kanker paru. Diharapkan ada penelitian berkelanjutan untuk meningkatkan status kesehatan global, khususnya pada pasien NSCLC.

Keywords

quercetin; non-small cell lung cancer; Src target; lung cancer

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References

Almatroodi, S.A., Alsahli, M.A., Almatroudi, A., Verma, A.K., Aloliqi, A., Allemailem, K.S., Khan, A.A., Rahmani, A.H., 2021. Potential therapeutic targets of quercetin, a plant flavonol, and its role in the therapy of various types of cancer through the modulation of various cell signaling pathways. Molecules 26. https://doi.org/10.3390/molecules26051315

Barta, J.A., Powell, C.A., Wisnivesky, J.P., 2019. Global epidemiology of lung cancer. Ann. Glob. Heal. https://doi.org/10.5334/aogh.2419

Beck, J.T., Ismail, A., Tolomeo, C., 2014. Targeting the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway: An emerging treatment strategy for squamous cell lung carcinoma. Cancer Treat. Rev. https://doi.org/10.1016/j.ctrv.2014.06.006

Chen, Y., Huang, Y., Kanwal, M., Li, G., Yang, J., Niu, H., Li, Z., Ding, X., 2019. MUC16 in non-small cell lung cancer patients affected by familial lung cancer and indoor air pollution: Clinical characteristics and cell behaviors. Transl. Lung Cancer Res. https://doi.org/10.21037/tlcr.2019.07.10

Cheng, E., Whitsett, T.G., Tran, N.L., Winkles, J.A., 2015. The TWEAK receptor Fn14 is an Src-inducible protein and a positive regulator of Src-driven cell invasion. Mol. Cancer Res. https://doi.org/10.1158/1541-7786.MCR-14-0411

Dasari, S., Bernard Tchounwou, P., 2014. Cisplatin in cancer therapy: Molecular mechanisms of action. Eur. J. Pharmacol. https://doi.org/10.1016/j.ejphar.2014.07.025

Deng, X.H., Song, H.Y., Zhou, Y.F., Yuan, G.Y., Zheng, F.J., 2013. Effects of quercetin on the proliferation of breast cancer cells and expression of survivin in vitro. Exp. Ther. Med. https://doi.org/10.3892/etm.2013.1285

Dong, Y., Yang, J., Yang, L., Li, P., 2020. Quercetin Inhibits the Proliferation and Metastasis of Human Non-Small Cell Lung Cancer Cell Line: The Key Role of Src-Mediated Fibroblast Growth Factor-Inducible 14 (Fn14)/Nuclear Factor kappa B (NF-κB) pathway. Med. Sci. Monit. https://doi.org/10.12659/MSM.920537

F.M., J., G.E., G., 2007. Src family nonreceptor tyrosine kinases as molecular targets for cancer therapy. Anticancer. Agents Med. Chem. 7.

Ferlay, J., Colombet, M., Soerjomataram, I., Mathers, C., Parkin, D.M., Piñeros, M., Znaor, A., Bray, F., 2019. Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods. Int. J. Cancer. https://doi.org/10.1002/ijc.31937

Funakoshi-Tago, M., Tago, K., Andoh, K., Sonoda, Y., Tominaga, S., Kasahara, T., 2005. Functional role of c-Src in IL-1-induced NF-kappa B activation: c-Src is a component of the IKK complex. J. Biochem. 137, 189–197.

Gao, P., Niu, N., Wei, T., Tozawa, H., Chen, X., Zhang, C., Zhang, J., Wada, Y., Kapron, C.M., Liu, J., 2017. The roles of signal transducer and activator of transcription factor 3 in tumor angiogenesis. Oncotarget. https://doi.org/10.18632/oncotarget.19932

Giaccone, G., Zucali, P.A., 2008. Src as a potential therapeutic target in non-small-cell lung cancer. Ann. Oncol. https://doi.org/10.1093/annonc/mdn048

Hoesel, B., Schmid, J.A., 2013. The complexity of NF-κB signaling in inflammation and cancer. Mol. Cancer. https://doi.org/10.1186/1476-4598-12-86

Hystad, P., Demers, P.A., Johnson, K.C., Carpiano, R.M., Brauer, M., 2013. Long-term residential exposure to air pollution and lung cancer risk. Epidemiology. https://doi.org/10.1097/EDE.0b013e3182949ae7

Jean, C., Chen, X.L., Nam, J.O., Tancioni, I., Uryu, S., Lawson, C., Ward, K.K., Walsh, C.T., Miller, N.L.G., Ghassemian, M., Turowski, P., Dejana, E., Weis, S., Cheresh, D.A., Schlaepfer, D.D., 2014. Inhibition of endothelial FAK activity prevents tumor metastasis by enhancing barrier function. J. Cell Biol. https://doi.org/10.1083/jcb.201307067

Kemenkes RI, 2017. Pedoman Nasional Pelayanan Kedokteran Kanker Paru, komite penanggulangan kanker nasional.

Kenfield, S.A., Wei, E.K., Stampfer, M.J., Rosner, B.A., Colditz, G.A., 2008. Comparison of aspects of smoking among the four histological types of lung cancer. Tob. Control. https://doi.org/10.1136/tc.2007.022582

Kopustinskiene, D.M., Jakstas, V., Savickas, A., Bernatoniene, J., 2020. Flavonoids as anticancer agents. Nutrients. https://doi.org/10.3390/nu12020457

Li, C., Zhang, W.J., Frei, B., 2016. Quercetin inhibits LPS-induced adhesion molecule expression and oxidant production in human aortic endothelial cells by p38-mediated Nrf2 activation and antioxidant enzyme induction. Redox Biol. 9. https://doi.org/10.1016/j.redox.2016.06.006

Li, L.H., Wu, L.J., Tashiro, S.I., Onodera, S., Uchiumi, F., Ikejima, T., 2006. The roles of Akt and MAPK family members in silymarin’s protection against UV-induced A375-S2 cell apoptosis. Int. Immunopharmacol. 6. https://doi.org/10.1016/j.intimp.2005.08.003

López-Cima, M.F., García-Pérez, J., Pérez-Gómez, B., Aragonés, N., López-Abente, G., Tardón, A., Pollán, M., 2011. Lung cancer risk and pollution in an industrial region of Northern Spain: A hospital-based case-control study. Int. J. Health Geogr. https://doi.org/10.1186/1476-072X-10-10

McGonigle, N., 2020. Lung cancer. Surg. (United Kingdom). https://doi.org/10.1016/j.mpsur.2020.03.008

NCCN, 2016. NCCN Clinical Practice Guidelines in Oncology-Non-small cell lung cancer, NCCN.

Norouzi, S., Gorgi Valokala, M., Mosaffa, F., Zirak, M.R., Zamani, P., Behravan, J., 2018. Crosstalk in cancer resistance and metastasis. Crit. Rev. Oncol. Hematol. https://doi.org/10.1016/j.critrevonc.2018.09.017

Organization, W.H., 2020. WHO | Cancer Key Facts [WWW Document]. WHO. URL https://www.who.int/health-topics/cancer#tab=tab_1

Park, S., 2015. Polyphenol compound as a transcription factor inhibitor. Nutrients. https://doi.org/10.3390/nu7115445

Priego, S., Feddi, F., Ferrer, P., Mena, S., Benlloch, M., Ortega, A., Carretero, J., Obrador, E., Asensi, M., Estrela, J.M., 2008. Natural polyphenols facilitate elimination of HT-29 colorectal cancer xenografts by chemoradiotherapy: A Bcl-2- and superoxide dismutase 2-dependent mechanism. Mol. Cancer Ther. 7. https://doi.org/10.1158/1535-7163.MCT-08-0363

Raffa, D., Maggio, B., Raimondi, M.V., Plescia, F., Daidone, G., 2017. Recent discoveries of anticancer flavonoids. Eur. J. Med. Chem. https://doi.org/10.1016/j.ejmech.2017.07.034

Ramos, S., 2007. Effects of dietary flavonoids on apoptotic pathways related to cancer chemoprevention. J. Nutr. Biochem. https://doi.org/10.1016/j.jnutbio.2006.11.004

Rauf, A., Imran, M., Khan, I.A., ur-Rehman, M., Gilani, S.A., Mehmood, Z., Mubarak, M.S., 2018. Anticancer potential of quercetin: A comprehensive review. Phyther. Res. https://doi.org/10.1002/ptr.6155

Testa, U., Castelli, G., Pelosi, E., 2018. Lung cancers: Molecular characterization, clonal heterogeneity and evolution, and cancer stem cells. Cancers (Basel). https://doi.org/10.3390/cancers10080248

Wang, W., Liu, F., Wang, Chaoyang, Wang, Chengde, Tang, Y., Jiang, Z., 2018. Src promotes metastasis of human non-small cell lung cancer cells through Fn14-mediated NF-κB signaling. Med. Sci. Monit. https://doi.org/10.12659/MSM.906266

World Health Organization, 2020. Estimated number of new cases in 2020, worldwide, both sexes, all ages [WWW Document]. Int. Agency Res. Cancer. URL https://gco.iarc.fr/today/online-analysis-table?v=2020&mode=cancer&mode_population=continents&population=900&populations=900&key=asr&sex=0&cancer=39&type=0&statistic=5&prevalence=0&population_group=0&ages_group%5B%5D=0&ages_group%5B%5D=17&group_cancer=1&i (accessed 1.24.20).

Wu, T.C., Chan, S.T., Chang, C.N., Yu, P.S., Chuang, C.H., Yeh, S.L., 2018. Quercetin and chrysin inhibit nickel-induced invasion and migration by downregulation of TLR4/NF-κB signaling in A549 cells. Chem. Biol. Interact. https://doi.org/10.1016/j.cbi.2018.07.010

Xingyu, Z., Peijie, M., Dan, P., Youg, W., Daojun, W., Xinzheng, C., Xijun, Z., Yangrong, S., 2016. Quercetin suppresses lung cancer growth by targeting Aurora B kinase. Cancer Med. https://doi.org/10.1002/cam4.891

Yang, W.S., Jeong, D., Yi, Y.S., Lee, B.H., Kim, T.W., Htwe, K.M., Kim, Y.D., Yoon, K.D., Hong, S., Lee, W.S., Cho, J.Y., 2014. Myrsine seguinii ethanolic extract and its active component quercetin inhibit macrophage activation and peritonitis induced by LPS by targeting to Syk/Src/IRAK-1. J. Ethnopharmacol. 151. https://doi.org/10.1016/j.jep.2013.12.033

Yuan, H., Ma, Q., Ye, L., Piao, G., 2016. The traditional medicine and modern medicine from natural products. Molecules. https://doi.org/10.3390/molecules21050559



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