Biomolecules & Therapeutics

  • 제31권6호
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  • Pages.655-660
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  • 2023
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  • 1976-9148(pISSN)
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  • 2005-4483(eISSN)
한국응용약물학회 (The Korean Society of Applied Pharmacology)
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Stimulatory Anticancer Effect of Resveratrol Mediated by G Protein-Coupled Estrogen Receptor in Colorectal Cancer

  • Nayun Kim (College of Pharmacy, Duksung Women's University) ;
  • Junhye Kwon (Department of Radiological & Clinical Research, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences (KIRAMS)) ;
  • Ui Sup Shin (Department of Surgery, Korea Cancer Center Hospital, KIRAMS) ;
  • Joohee Jung (College of Pharmacy, Duksung Women's University)
  • 투고 : 2023.03.30
  • 심사 : 2023.05.23
  • 발행 : 2023.11.01
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초록

Colorectal cancer (CRC) is one of the most high-risk cancers; however, it has been suggested that estrogen signaling in CRC could have a protective effect. Therefore, we focused on the function of the G protein-coupled estrogen receptor (GPER) among the estrogen receptors in CRC. In this study, we investigated the therapeutic effect of resveratrol via GPER in CRC (RKO and WiDr) cells, CRC cell-derived xenograft models, and organoids (30T and 33T). Resveratrol significantly suppressed cell viability and proliferation in highly GPER-expressing RKO cells compared to that in low GPER-expressing WiDr cells. In xenograft models, resveratrol also delayed tumor growth and exhibited a high survival rate depending on GPER expression in RKO-derived tumors. Furthermore, resveratrol significantly inhibited the viability of organoids with high GPER expression. Additionally, the anticancer effect of resveratrol on CRC showed that resveratrol rapidly responded to GPER, while increasing the expression of p-ERK and Bax and cleaving PARP proteins.

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과제정보

This research was supported by an NRF grant funded by MSIT (NRF-2021R1A2C2004535), the Priority Research Centers Program through NRF funded by the Ministry of Education (2016R1A6A1A03007648) (J.J.), and a grant of the KIRAMS funded by MSIT, the Republic of Korea (No. 50542-2022) (U.S.).

참고문헌

  1. Abancens, M., Harvey, B. J. and McBryan, J. (2022) GPER agonist G1 prevents Wnt-induced JUN upregulation in HT29 colorectal cancer cells. Int. J. Mol. Sci. 23, 12581.
  2. Arai, Y., Watanabe, S., Kimira, M., Shimoi, K., Mochizuki, R. and Kinae, N. (2000) Dietary intakes of flavonols, flavones and isoflavones by Japanese women and the inverse correlation between quercetin intake and plasma LDL cholesterol concentration. J. Nutr. 130, 2243-2250. https://doi.org/10.1093/jn/130.9.2243
  3. Bahadori, M., Baharara, J. and Amini, E. (2016) Anticancer properties of chrysin on colon cancer cells, in vitro and in vivo with modulation of caspase-3, -9, Bax and Sall4. Iran. J. Biotechnol. 14, 177-184. https://doi.org/10.15171/ijb.1374
  4. Broutier, L., Mastrogiovanni, G., Verstegen, M. M., Francies, H. E., Gavarro, L. M., Bradshaw, C. R., Allen, G. E., Arnes-Benito, R., Sidorova, O., Gaspersz, M. P., Georgakopoulos, N., Koo, B. K., Dietmann, S., Davies, S. E., Praseedom, R. K., Lieshout, R., IJzermans, J. N. M., Wigmore, S. J., Saeb-Parsy, K., Garnett, M. J., van der Laan, L. J. and Huch, M. (2017) Human primary liver cancerderived organoid cultures for disease modeling and drug screening. Nat. Med. 23, 1424-1435. https://doi.org/10.1038/nm.4438
  5. Chavez, E., Reyes-Gordillo, K., Segovia, J., Shibayama, M., Tsutsumi, V., Vergara, P., Moreno, M. G. and Muriel, P. (2008) Resveratrol prevents fibrosis, NF-kappaB activation and TGF-beta increases induced by chronic CCl4 treatment in rats. J. Appl. Toxicol. 28, 35-43. https://doi.org/10.1002/jat.1249
  6. Cruz-Nova, P., Schnoor, M., Correa-Basurto, J., Bello, M., Briseno-Diaz, P., Rojo-Dominguez, A., Ortiz-Mendoza, C. M., Guerrero-Aguirre, J., Garcia-Vazquez, F. J., Hernandez-Rivas, R., Thompson-Bonilla, M. D. R. and Vargas, M. (2018) The small organic molecule C19 binds and strengthens the KRAS4b-PDEδ complex and inhibits growth of colorectal cancer cells in vitro and in vivo. BMC Cancer 18, 1056.
  7. D'Arrigo, G., Gianquinto, E., Rossetti, G., Cruciani, G., Lorenzetti, S. and Spyrakis, F. (2021) Binding of androgen- and estrogen-like flavonoids to their cognate (non)nuclear receptors: a comparison by computational prediction. Molecules 26, 1613.
  8. Di Leo, A., Messa, C., Cavallini, A. and Linsalata, M. (2001) Estrogens and colorectal cancer. Curr. Drug Targets Immune Endocr. Metabol. Disord. 1, 1-12.
  9. Fu, Y., Ye, Y., Zhu, G., Xu, Y., Sun, J., Wu, H., Feng, F., Wen, Z., Jiang, S., Li, Y. and Zhang, Q. (2021) Resveratrol induces human colorectal cancer cell apoptosis by activating the mitochondrial pathway via increasing reactive oxygen species. Mol. Med. Rep. 23, 170.
  10. Gilligan, L. C., Rahman, H. P., Hewitt, A. M., Sitch, A. J., Gondal, A., Arvaniti, A., Taylor, A. E., Read, M. L., Morton, D. G. and Foster, P. A. (2017) Estrogen activation by steroid sulfatase increases colorectal cancer proliferation via GPER. J. Clin. Endocrinol. Metab. 102, 4435-4447. https://doi.org/10.1210/jc.2016-3716
  11. Hsu, L. H., Chu, N. M., Lin, Y. F. and Kao, S. H. (2019) G-protein coupled estrogen receptor in breast cancer. Int. J. Mol. Sci. 20, 306.
  12. Ji, Q., Liu, X., Han, Z., Zhou, L., Sui, H., Yan, L., Jiang, H., Ren, J., Cai, J. and Li, Q. (2015) Resveratrol suppresses epithelial-to-mesenchymal transition in colorectal cancer through TGF-β1/Smads signaling pathway mediated Snail/E-cadherin expression. BMC Cancer 15, 97.
  13. Jung, J. (2019) Role of G protein-coupled estrogen receptor in cancer progression. Toxicol. Res. 35, 209-214. https://doi.org/10.5487/TR.2019.35.3.209
  14. Khan, N., Syed, D. N., Ahmad, N. and Mukhtar, H. (2013) Fisetin: a dietary antioxidant for health promotion. Antioxid. Redox Signal. 19, 151-162. https://doi.org/10.1089/ars.2012.4901
  15. Khil, H., Kim, S. M., Hong, S., Gil, H. M., Cheon, E., Lee, D. H., Kim, Y. A. and Keum, N. (2021) Time trends of colorectal cancer incidence and associated lifestyle factors in South Korea. Sci. Rep. 11, 2413.
  16. Ko, J. H., Sethi, G., Um, J. Y., Shanmugam, M. K., Arfuso, F., Kumar, A. P., Bishayee, A. and Ahn, K. S. (2017) The role of resveratrol in cancer therapy. Int. J. Mol. Sci. 18, 2589.
  17. Kondo, J. and Inoue, M. (2019) Application of cancer organoid model for drug screening and personalized therapy. Cells 8, 470.
  18. Kwon, J., Oh, S., Park, M., Kong, J. S., Lee, S., Lee, H., Kim, Y., Kang, K. T., Shin, U. S. and Jung, J. (2021) Advanced xenograft model with cotransplantation of patient-derived organoids and endothelial colony-forming cells for precision medicine. J. Oncol. 2021, 9994535.
  19. Liu, Q., Chen, Z., Jiang, G., Zhou, Y., Yang, X., Huang, H., Liu, H., Du, J. and Wang, H. (2017) Epigenetic down regulation of G protein-coupled estrogen receptor (GPER) functions as a tumor suppressor in colorectal cancer. Mol. Cancer 16, 87. https://doi.org/10.1186/s12943-017-0654-3
  20. Lucas, J., Hsieh, T. C., Halicka, H. D., Darzynkiewicz, Z. and Wu, J. M. (2018) Upregulation of PD-L1 expression by resveratrol and piceatannol in breast and colorectal cancer cells occurs via HDAC3/p300-mediated NF-κB signaling. Int. J. Oncol. 53, 1469-1480. https://doi.org/10.3892/ijo.2018.4512
  21. Luo, J. and Liu, D. (2020) Does GPER really function as a G proteincoupled estrogen receptor in vivo? Front. Endocrinol. (Lausanne) 11, 148.
  22. Meng, T., Xiao, D., Muhammed, A., Deng, J., Chen, L. and He, J. (2021) Anti-inflammatory action and mechanisms of resveratrol. Molecules 26, 229.
  23. Park, M., Kwon, J., Shin, H. J., Moon, S. M., Kim, S. B., Shin, U. S., Han, Y. H. and Kim, Y. (2020) Butyrate enhances the efficacy of radiotherapy via FOXO3A in colorectal cancer patient-derived organoids. Int. J. Oncol. 57, 1307-1318. https://doi.org/10.3892/ijo.2020.5132
  24. Qiu, Y. A., Xiong, J. and Yu, T. (2021) Role of G protein-coupled estrogen receptor in digestive system carcinomas: a minireview. Onco Targets Ther. 14, 2611-2622. https://doi.org/10.2147/OTT.S291896
  25. Ren, B., Kwah, M. X., Liu, C., Ma, Z., Shanmugam, M. K., Ding, L., Xiang, X., Ho, P. C., Wang, L., Ong, P. S. and Goh, B. C. (2021) Resveratrol for cancer therapy: challenges and future perspectives. Cancer Lett. 515, 63-72. https://doi.org/10.1016/j.canlet.2021.05.001
  26. Sakalem, M. E., De Sibio, M. T., da Costa, F. A. D. S. and de Oliveira, M. (2021) Historical evolution of spheroids and organoids, and possibilities of use in life sciences and medicine. Biotechnol. J. 16, e2000463.
  27. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A. and Bray, F. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 71, 209-249. https://doi.org/10.3322/caac.21660
  28. Vernousfaderani, E. K., Akhtari, N., Rezaei, S., Rezaee, Y., Shiranirad, S., Mashhadi, M., Hashemi, A., Khankandi, H. P. and Behzad, S. (2021) Resveratrol and colorectal cancer: a molecular approach to clinical researches. Curr. Top. Med. Chem. 21, 2634-2646. https://doi.org/10.2174/1568026621666211105093658
  29. Vo, D. H., Hartig, R., Weinert, S., Haybaeck, J. and Nass, N. (2019) G-protein-coupled estrogen receptor (GPER)-specific agonist G1 induces ER stress leading to cell death in MCF-7 cells. Biomolecules 9, 503.
  30. Xia, N., Daiber, A., Forstermann, U. and Li, H. (2017) Antioxidant effects of resveratrol in the cardiovascular system. Br. J. Pharmacol. 174, 1633-1646. https://doi.org/10.1111/bph.13492
  31. Zhou, G., Yang, J. and Song, P. (2019) Correlation of ERK/MAPK signaling pathway with proliferation and apoptosis of colon cancer cells. Oncol. Lett. 17, 2266-2270.