DOI QR코드

DOI QR Code

Urushiol V Suppresses Cell Proliferation and Enhances Antitumor Activity of 5-FU in Human Colon Cancer Cells by Downregulating FoxM1

  • Jeong, Ji Hye (Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women's University) ;
  • Ryu, Jae-Ha (Research Institute of Pharmaceutical Sciences and College of Pharmacy, Sookmyung Women's University)
  • 투고 : 2022.01.18
  • 심사 : 2022.02.09
  • 발행 : 2022.05.01

초록

Colorectal cancer (CRC) is one of the most common malignant tumor. 5-FU is commonly used for the treatment of CRC. However, the development of drug resistance in tumor chemotherapy can seriously reduce therapeutic efficacy of 5-FU. Recent data show that FoxM1 is associated with 5-FU resistance in CRC. FoxM1 plays a critical role in the carcinogenesis and drug resistance of several malignancies. It has been reported that urushiol V isolated from the cortex of Rhus verniciflua Stokes is cytotoxic to several types of cancer cells. However, the underlying molecular mechanisms for its antitumor activity and its potential to attenuate the chemotherapeutic resistance in CRC cells remain unknown. Here, we found that urushiol V could inhibit the cell proliferation and induced S-phase arrest of SW480 colon cancer cells. It inhibited protein expression level of FoxM1 through activation of AMPK. We also investigated the combined effect of urushiol V and 5-FU. The combination treatment reduced FoxM1 expression and consequently reduced cell growth and colony formation in 5-FU resistant colon cancer cells (SW480/5-FUR). Taken together, these result suggest that urushiol V from Rhus verniciflua Stokes can suppress cell proliferation by inhibiting FoxM1 and enhance the antitumor capacity of 5-FU. Therefore, urushiol V may be a potential bioactive compound for CRC therapy.

키워드

과제정보

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (grant number 2021R1A6A3A01086698).

참고문헌

  1. Bhat, U. G., Halasi, M. and Gartel, A. L. (2009) FoxM1 is a general target for proteasome inhibitors. PLoS ONE 4, e6593. https://doi.org/10.1371/journal.pone.0006593
  2. Chan, D. W., Yu, S. Y., Chiu, P. M., Yao, K. M., Liu, V. W., Cheung, A. N. and Ngan, H. Y. (2008) Over-expression of FOXM1 transcription factor is associated with cervical cancer progression and pathogenesis. J. Pathol. 215, 245-252. https://doi.org/10.1002/path.2355
  3. Choi, H. S., Seo, H. S., Kim, S. R., Choi, Y. K., Jang, B. H., Shin, Y. C. and Ko, S. G. (2014) Anti-inflammatory and anti-proliferative effects of Rhus verniciflua Stokes in RAW264.7 cells. Mol. Med. Rep. 9, 311-315. https://doi.org/10.3892/mmr.2013.1775
  4. Choi, J. Y., Park, C. S., Choi, J. O., Rhim, H. S. and Chun, H. J. (2001) Cytotoxic effect of urushiol on human ovarian cancer cells. J. Microbiol. Biotechnol. 11, 399-405.
  5. Chu, E., Koeller, D. M., Johnston, P. G., Zinn, S. and Allegra, C. J. (1993) Regulation of thymidylate synthase in human colon cancer cells treated with 5-fluorouracil and interferon-gamma. Mol. Pharmacol. 43, 527-533.
  6. Chu, X. Y., Zhu, Z. M., Chen, L. B., Wang, J. H., Su, Q. S., Yang, J. R., Lin, Y., Xue, L. J., Liu, X. B. and Mo, X. B. (2012) FOXM1 expression correlates with tumor invasion and a poor prognosis of colorectal cancer. Acta Histochem. 114, 755-762. https://doi.org/10.1016/j.acthis.2012.01.002
  7. Drake, J. C., Allegra, C. J. and Johnston, P. G. (1993) Immunological quantitation of thymidylate synthase-FdUMP-5,10-methylenetetrahydrofolate ternary complex with the monoclonal antibody TS 106. Anticancer Drugs 4, 431-435. https://doi.org/10.1097/00001813-199308000-00002
  8. el-Deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., Lin, D., Mercer, W. E., Kinzler, K. W. and Vogelstein, B. (1993) WAF1, a potential mediator of p53 tumor suppression. Cell 75, 817-825. https://doi.org/10.1016/0092-8674(93)90500-p
  9. ElSohly, M. A., Adawadkar, P. D., Ma, C. Y. and Turner, C. E. (1982) Separation and characterization of poison ivy and poison oak urushiol components. J. Nat. Prod. 45, 532-538. https://doi.org/10.1021/np50023a004
  10. Gingras, A. C., Raught, B., Gygi, S. P., Niedzwiecka, A., Miron, M., Burley, S. K., Polakiewicz, R. D., Wyslouch-Cieszynska, A., Aebersold, R. and Sonenberg, N. (2001) Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 15, 2852-2864. https://doi.org/10.1101/gad.912401
  11. Gong, C., Tsoi, H., Mok, K. C., Cheung, J., Man, E. P. S., Fujino, K., Wong, A., Lam, E. W. F. and Khoo, U. S. (2020) Phosphorylation independent eIF4E translational reprogramming of selective mRNAs determines tamoxifen resistance in breast cancer. Oncogene 39, 3206-3217. https://doi.org/10.1038/s41388-020-1210-y
  12. Hong, D. H., Han, S. B., Lee, C. W., Park, S. H., Jeon, Y. J., Kim, M. J., Kwak, S. S. and Kim, H. M. (1999) Cytotoxicity of urushiols isolated from sap of Korean lacquer tree (Rhus vernicifera Stokes) Arch. Pharm. Res. 22, 638-641. https://doi.org/10.1007/BF02975339
  13. Jeong, J. H. and Ryu, J. H. (2020) Broussoflavonol B from Broussonetia kazinoki Siebold exerts anti-pancreatic cancer activity through downregulating FoxM1. Molecules 25, 2328. https://doi.org/10.3390/molecules25102328
  14. Kalin, T. V., Wang, I. C., Ackerson, T. J., Major, M. L., Detrisac, C. J., Kalinichenko, V. V., Lyubimov, A. and Costa, R. H. (2006) Increased levels of the FoxM1 transcription factor accelerate development and progression of prostate carcinomas in both TRAMP and LADY transgenic mice. Cancer Res. 66, 1712-1720. https://doi.org/10.1158/0008-5472.CAN-05-3138
  15. Kim, I. M., Ackerson, T., Ramakrishna, S., Tretiakova, M., Wang, I. C., Kalin, T. V., Major, M. L., Gusarova, G. A., Yoder, H. M., Costa, R. H. and Kalinichenko, V. V. (2006) The Forkhead Box m1 transcription factor stimulates the proliferation of tumor cells during development of lung cancer. Cancer Res. 66, 2153-2161. https://doi.org/10.1158/0008-5472.CAN-05-3003
  16. Kim, M. J., Choi, Y. H., Kim, W. G. and Kwak, S. S. (1997) Antioxidative activity of urushiol derivatives from the sap of lacquer tree (Rhus vernicifera Stokes). Korean J. Plant Resour. 10, 227-230.
  17. Kim, S., Kim, D. H., Lee, S. H., Kim, M. J., Yoon, J. H., Chung, H. Y., Na, C. S. and Kim, N. D. (2013) Urushiol induces apoptosis via a p53-dependent pathway in human gastric cancer cells. J. Cancer Prev. 18, 169-176. https://doi.org/10.15430/JCP.2013.18.2.169
  18. Kitts, D. D. and Lim, K. T. (2001) Antitumorigenic and cytotoxic properties of an ethanol extract derived from Rhus verniciflua Stokes (RVS). J. Toxicol. Environ. Health A 64, 357-371. https://doi.org/10.1080/152873901316981330
  19. Klinhom-On, N., Seubwai, W., Sawanyawisuth, K., Obchoei, S., Mahalapbutr, P. and Wongkham, S. (2021) FOXM1 inhibitor, Siomycin A, synergizes and restores 5-FU cytotoxicity in human cholangiocarcinoma cell lines via targeting thymidylate synthase. Life Sci. 86, 120072.
  20. Koo, C. Y., Muir, K. W. and Lam, E. W. (2012) FOXM1: from cancer initiation to progression and treatment. Biochim. Biophys. Acta 1819, 28-37. https://doi.org/10.1016/j.bbagrm.2011.09.004
  21. Lee, D.-G., Kim, H. J., Jin, S., Kim, J. W., Whang, Y. M., Lee, T. J. and Chang, I. H. (2017) NBR1 and KIF14 downstream of the mammarian target of rapamycin pathway predict recurrence in nonmuscle invasive low grade urothelial carcinoma of the bladder. Korean J. Urol. Oncol. 15, 28-37. https://doi.org/10.22465/kjuo.2017.15.1.28
  22. Lee, J. O., Moon, J. W., Lee, S. K., Kim, S. M., Kim, N., Ko, S. G., Kim, H. S. and Park, S. H. (2014) Rhus verniciflua extract modulates survival of MCF-7 breast cancer cells through the modulation of AMPK-pathway. Biol. Pharm. Bull. 37, 794-801. https://doi.org/10.1248/bpb.b13-00893
  23. Lim, K. T., Hu, C. and Kitts, D. D. (2001) Antioxidant activity of a Rhus verniciflua Stokes ethanol extract. Food Chem. Toxicol. 39, 229-237. https://doi.org/10.1016/S0278-6915(00)00135-6
  24. Longley, D. B., Harkin, D. P. and Johnston, P. G. (2003) 5-fluorouracil: mechanisms of action and clinical strategies. Nat. Rev. Cancer 3, 330-338. https://doi.org/10.1038/nrc1074
  25. Ma, X. M., Lu, R. and Miyakoshi, T. (2012) Recent advances in research on lacquer allergy. Allergol. Int. 61, 45-50. https://doi.org/10.2332/allergolint.11-RA-0324
  26. Mihaylova, M. M. and Shaw, R. J. (2011) The AMPK signalling pathway coordinates cell growth, autophagy and metabolism. Nat. Cell Biol. 13, 1016-1023. https://doi.org/10.1038/ncb2329
  27. Motoshima, H., Goldstein, B. J., Igata, M. and Araki, E. (2006) AMPK and cell proliferation--AMPK as a therapeutic target for atherosclerosis and cancer. J. Physiol. 574, 63-71. https://doi.org/10.1113/jphysiol.2006.108324
  28. Peters, G. J., Backus, H. H. J., Freemantle, S., van Triest, B., CodacciPisanelli, G., van der Wilt, C. L., Smid, K., Lunec, J., Calvert, A. H., Marsh, S., McLeod, H. L., Bloemena, E., Meijer, S., Jansen, G., van Groeningen, C. J. and Pinedo, H. M. (2002) Induction of thymidylate synthase as a 5-fluorouracil resistance mechanism. Biochim. Biophys. Acta 1587, 194-205. https://doi.org/10.1016/S0925-4439(02)00082-0
  29. Popat, S., Matakidou, A. and Houlston, R. S. (2004) Thymidylate synthase expression and prognosis in colorectal cancer: a systematic review and meta-analysis. J. Clin. Oncol. 22, 529-536. https://doi.org/10.1200/JCO.2004.05.064
  30. Suk, K. T., Baik, S. K., Kim, H. S., Park, S. M., Paeng, K. J., Uh, Y., Jang, I. H., Cho, M. Y., Choi, E. H., Kim, M. J. and Ham, Y. L. (2011) Antibacterial effects of the urushiol component in the sap of the lacquer tree (Rhus verniciflua Stokes) on Helicobacter pylori. Helicobacter 16, 434-443. https://doi.org/10.1111/j.1523-5378.2011.00864.x
  31. 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
  32. Tian, T., Li, X. and Zhang, J. (2019) mTOR signaling in cancer and mTOR inhibitors in solid tumor targeting therapy. Int. J. Mol. Sci. 20, 755. https://doi.org/10.3390/ijms20030755
  33. Varghese, V., Magnani, L., Harada-Shoji, N., Mauri, F., Szydlo, R. M., Yao, S., Lam, E. W. F. and Kenny, L. M. (2019) FOXM1 modulates 5-FU resistance in colorectal cancer through regulating TYMS expression. Sci. Rep. 9, 1505. https://doi.org/10.1038/s41598-018-38017-0
  34. Wakabayashi, T., Hu, D. L., Tagawa, Y., Sekikawa, K., Iwakura, Y., Hanada, K. and Nakane, A. (2005) IFN-gamma and TNF-alpha are involved in urushiol-induced contact hypersensitivity in mice. Immunol. Cell Biol. 83, 18-24. https://doi.org/10.1111/j.1440-1711.2005.01310.x
  35. Wang, L., Wang, Y., Du, X., Yao, Y., Wang, L. and Jia, Y. (2019) MiR-216b suppresses cell proliferation, migration, invasion, and epithelial-mesenchymal transition by regulating FOXM1 expression in human non-small cell lung cancer. OncoTargets Ther. 12, 2999-3009. https://doi.org/10.2147/OTT.S202523
  36. Xia, N., Tan, W. F., Peng, Q. Z. and Cai, H. N. (2019) MiR-374b reduces cell proliferation and cell invasion of cervical cancer through regulating FOXM1. Eur. Rev. Med. Pharmacol. Sci. 23, 513-521.
  37. Xie, T., Geng, J., Wang, Y., Wang, L., Huang, M., Chen, J., Zhang, K., Xue, L., Liu, X., Mao, X., Chen, Y., Wang, Q., Dai, T., Ren, L., Yu, H., Wang, R., Chen, L., Chen, C. and Chu, X. (2017) FOXM1 evokes 5-fluorouracil resistance in colorectal cancer depending on ABCC10. Oncotarget 8, 8574-8589. https://doi.org/10.18632/oncotarget.14351
  38. Yang, C., Chen, H., Yu, L., Shan, L., Xie, L., Hu, J., Chen, T. and Tan, Y. (2013) Inhibition of FOXM1 transcription factor suppresses cell proliferation and tumor growth of breast cancer. Cancer Gene Ther. 20, 117-124. https://doi.org/10.1038/cgt.2012.94
  39. Yoo, H. and Roh, J. (1977) Compendium of Prescriptions from the Countryside (Hyangyakjipseongbang), Vol. 1433. Hangrimchulpansa, Seoul, Korea.
  40. Yung, M. M., Chan, D. W., Liu, V. W., Yao, K. M. and Ngan, H. Y. (2013) Activation of AMPK inhibits cervical cancer cell growth through AKT/FOXO3a/FOXM1 signaling cascade. BMC Cancer 13, 327. https://doi.org/10.1186/1471-2407-13-327
  41. Zhang, H., Zhong, H., Li, L., Ji, W. and Zhang, X. (2016) Overexpressed transcription factor FOXM1 contributes to the progression of colorectal cancer. Mol. Med. Rep. 13, 2696-2700. https://doi.org/10.3892/mmr.2016.4875
  42. Zhang, N., Yin, Y., Xu, S. J. and Chen, W. S. (2008) 5-Fluorouracil: mechanisms of resistance and reversal strategies. Molecules 13, 1551-1569. https://doi.org/10.3390/molecules13081551