Antitumor activity of Coptis chinensis rhizome extract against PANC-1 cells

Authors

DOI:

https://doi.org/10.2298/ABS250425016J

Keywords:

anti-cancer, berberine, Coptis chinensis, FoxM1, pancreatic cancer

Abstract

Paper description:

  • Dysregulation of Forkhead box M1 (FoxM1) is associated with poor prognosis and metastasis in pancreatic cancer.
  • Effects of Coptis chinensis rhizome extract and its principal isoquinoline alkaloid berberine on PANC-1 pancreatic cancer cells were investigated by focusing on FoxM1 expression regulation.
  • The extract exhibited potential anti-pancreatic cancer activity, partially attributable to its principal constituent berberine, and was associated with FoxM1 downregulation.
  • Coptis chinensis rhizome extract and berberine, have therapeutic potential against human pancreatic cancer.

Abstract: The rhizome of Coptis chinensis is known for its antibacterial, anti-inflammatory, and anticancer activities. This study aimed to investigate the anti-pancreatic cancer activity of C. chinensis rhizome and elucidate the molecular mechanism involved in such activity. The C. chinensis rhizome extract (CRE) significantly inhibited the cell viability of PANC-1 pancreatic cancer cells and arrested the cell cycle at the G0/G1 phase. Western-blot analysis revealed that CRE downregulated the protein level of Forkhead box M1 (FoxM1), an oncogenic transcription factor, and its downstream target proteins such as cyclin D1, c-Myc, and survivin. Berberine was identified as the main component in CRE, effectively reducing cell viability and FoxM1 expression. These findings indicate that CRE and berberine can exert anticancer activity by downregulating FoxM1 expression in pancreatic cancer cells and that berberine may partially contribute to the anti-pancreatic cancer properties of CRE. This study highlights that C. chinensis rhizome extract and its main ingredient, berberine, might have therapeutic potential against pancreatic cancer.

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References

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-63. https://doi.org/10.3322/caac.21834

Qadir RMAB, Umair MB, Tariq UB, Ahmad A, Kiran W, Shahid MH. Unraveling pancreatic cancer: Epidemiology, risk factors, and global trends. Cureus. 2024;16(11):e72816. https://doi.org/10.7759/cureus.72816

Espona-Fiedler M, Patthey C, Lindblad S, Sarró I, Öhlund D. Overcoming therapy resistance in pancreatic cancer: New insights and future directions. Biochem Pharmacol. 2024;229:116492. https://doi.org/10.1016/j.bcp.2024.116492

Wierstra I. FOXM1 (Forkhead box M1) in tumorigenesis: overexpression in human cancer, implication in tumorigenesis, oncogenic functions, tumor-suppressive properties, and target of anticancer therapy. Adv Cancer Res. 2013;119:191-419. https://doi.org/10.1016/B978-0-12-407190-2.00016-2

Liao GB, Li XZ, Zeng S, Liu C, Yang SM, Yang L, Hu CJ, Bai JY. Regulation of the master regulator FOXM1 in cancer. Cell Commun Signal. 2018;16(1):57. https://doi.org/10.1186/s12964-018-0266-6

Song X, Fiati Kenston SS, Zhao J, Yang D, Gu Y. Roles of FoxM1 in cell regulation and breast cancer targeting therapy. Med Oncol. 2017;34(3):41. https://doi.org/10.1007/s12032-017-0888-3

Huang C, Du J, Xie K. FOXM1 and its oncogenic signaling in pancreatic cancer pathogenesis. Biochim Biophys Acta. 2014;1845(2):104-16. https://doi.org/10.1016/j.bbcan.2014.01.002

Wang X, Dou N, Wang J, Zhang Y, Li Y, Gao Y. FOXM1-induced miR-552 expression contributes to pancreatic cancer progression by targeting multiple tumor suppressor genes. Int J Biol Sci. 2021;17(4):915-25. https://doi.org/10.7150/ijbs.56733

Wang J, Wang L, Lou GH, Zeng HR, Hu J, Huang QW, Peng W, Yang XB. Coptidis Rhizoma: a comprehensive review of its traditional uses, botany, phytochemistry, pharmacology and toxicology. Pharm Biol. 2019;57(1):193-225. https://doi.org/10.1080/13880209.2019.1577466

Hu JP, Takahashi N, Yamada T. Coptidis rhizoma inhibits growth and proteases of oral bacteria. Oral Dis. 2000;6(5):297-302. https://doi.org/10.1111/j.1601-0825.2000.tb00142.x

Bao M, Bu Q, Pan M, Xu R, Chen Y, Yang Y, Wang C, Wang T. Coptidis rhizoma extract alleviates oropharyngeal candidiasis by gC1qR-EGFR/ERK/c-fos axis-induced endocytosis of oral epithelial cells. J Ethnopharmacol. 2024;331:118305. https://doi.org/10.1016/j.jep.2024.118305

Hung TC, Jassey A, Lin CJ, Liu CH, Lin CC, Yen MH, Lin LT. Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection. Viruses. 2018;10(12):669. https://doi.org/10.3390/v10120669

Kim JM, Jung HA, Choi JS, Lee NG. Identification of anti-inflammatory target genes of Rhizoma coptidis extract in lipopolysaccharide-stimulated RAW264.7 murine macrophage-like cells. J Ethnopharmacol. 2010;130(2):354-62. https://doi.org/10.1016/j.jep.2010.05.022

Xu Z, Feng W, Shen Q, Yu N, Yu K, Wang S, Chen Z, Shioda S, Guo Y. Rhizoma Coptidis and berberine as a natural drug to combat aging and aging-related diseases via anti-oxidation and AMPK activation. Aging Dis. 2017;8(6):760-77. https://doi.org/10.14336/AD.2016.0620

Kim SY, Park C, Kim MY, Ji SY, Hwangbo H, Lee H, Hong SH, Han MH, Jeong JW, Kim GY, Son CG, Cheong J, Choi YH. ROS-mediated anti-tumor effect of Coptidis Rhizoma against human hepatocellular carcinoma Hep3B cells and xenografts. Int J Mol Sci. 2021;22(9):4797. https://doi.org/10.3390/ijms22094797

Wang H, Zhang F, Ye F, Ma Y, Zhang DY. The effect of coptis chinensis on the signaling network in the squamous carcinoma cells. Front Biosci (Elite Ed). 2011;3(1):326-40. https://doi.org/10.2741/e248

Kim JH, Ko ES, Kim D, Park SH, Kim EJ, Rho J, Seo H, Kim MJ, Yang WM, Ha IJ, Park MJ, Lee JY. Cancer cell specific anticancer effects of Coptis chinensis on gefitinib resistant lung cancer cells are mediated through the suppression of Mcl 1 and Bcl 2. Int J Oncol. 2020;56(6):1540-50. https://doi.org/10.3892/ijo.2020.5025

Kim SY, Park C, Kim MY, Ji SY, Hwangbo H, Lee H, Hong SH, Han MH, Jeong JW, Kim GY, Son CG, Cheong J, Choi YH. ROS-Mediated Anti-Tumor Effect of Coptidis Rhizoma against Human Hepatocellular Carcinoma Hep3B Cells and Xenografts. Int J Mol Sci. 2021;22(9):4797. https://doi.org/10.3390/ijms22094797

Wang N, Tan HY, Li L, Yuen MF, Feng Y. Berberine and Coptidis Rhizoma as potential anticancer agents: Recent updates and future perspectives. J Ethnopharmacol. 2015;176:35-48. https://doi.org/10.1016/j.jep.2015.10.028

Wang Y, Liu Y, Du X, Ma H, Yao J. The anti-cancer mechanisms of berberine: A review. Cancer Manag Res. 2020;12:695-702. https://doi.org/10.2147/CMAR.S242329

Xu M, Ren L, Fan J, Huang L, Zhou L, Li X, Ye X. Berberine inhibits gastric cancer development and progression by regulating the JAK2/STAT3 pathway and downregulating IL-6. Life Sci. 2022;290:120266. https://doi.org/10.1016/j.lfs.2021.120266

Liu M, Yang Y, Kang W, Liu Y, Tao X, Li X, Pan Y. Berberine inhibits pancreatic intraepithelial neoplasia by inhibiting glycolysis via the adenosine monophosphate -activated protein kinase pathway. Eur J Pharmacol. 2022;915:174680. https://doi.org/10.1016/j.ejphar.2021.174680

Zhang YL, Zhang X, Miao XZ, Yuan YY, Gao J, Li X, Liu YG, Tan P. Coptisine suppresses proliferation and inhibits metastasis in human pancreatic cancer PANC-1 cells. J Asian Nat Prod Res. 2020;22(5):452-63. https://doi.org/10.1080/10286020.2019.1585820

Lee HJ, Son DH, Lee SK, Lee J, Jun CD, Jeon BH, Lee SK, Kim EC. Extract of Coptidis Rhizoma induces cytochrome-c dependent apoptosis in immortalized and malignant human oral keratinocytes. Phytother Res. 2006;20(9):773-9. https://doi.org/10.1002/ptr.1956

Kang YH, Lee JS, Lee NH, Kim SH, Seo CS, Son CG. Coptidis Rhizoma Extract Reverses 5-Fluorouracil Resistance in HCT116 Human Colorectal Cancer Cells via Modulation of Thymidylate Synthase. Molecules. 2021;26(7):1856. https://doi.org/10.3390/molecules26071856

Tan HY, Wang N, Tsao SW, Zhang Z, Feng Y. Suppression of vascular endothelial growth factor via inactivation of eukaryotic elongation factor 2 by alkaloids in Coptidis rhizome in hepatocellular carcinoma. Integr Cancer Ther. 2014;13(5):425-34. https://doi.org/10.1177/1534735413513635

Skotheim JM. Cell growth and cell cycle control. Mol Biol Cell. 2013;24(6):678. https://doi.org/10.1091/mbc.E13-01-0002

Jiang S, Fagman JB, Ma Y, Liu J, Vihav C, Engstrom C, Liu B, Chen C. A comprehensive review of pancreatic cancer and its therapeutic challenges. Aging (Albany NY). 2022;14(18):7635-49. https://doi.org/10.18632/aging.204310

Kolbeinsson HM, Chandana S, Wright GP, Chung M. Pancreatic cancer: A review of current treatment and novel therapies. J Invest Surg. 2023;36(1):2129884. https://doi.org/10.1080/08941939.2022.2129884

Zheng J, Guinter MA, Merchant AT, Wirth MD, Zhang J, Stolzenberg-Solomon RZ, Steck SE. Dietary patterns and risk of pancreatic cancer: a systematic review. Nutr Rev. 2017;75(11):883-908. https://doi.org/10.1093/nutrit/nux038

Kang YH, Lee JS, Lee NH, Kim SH, Seo CS, Son CG. Coptidis Rhizoma extract reverses 5-fluorouracil resistance in HCT116 human colorectal cancer cells via modulation of thymidylate synthase. Molecules. 2021;26(7):1856. https://doi.org/10.3390/molecules26071856

Li J, Ni L, Li B, Wang M, Ding Z, Xiong C, Lu X. Coptis Chinensis affects the function of glioma cells through the down-regulation of phosphorylation of STAT3 by reducing HDAC3. BMC Complement Altern Med. 2017;17(1):524. https://doi.org/10.1186/s12906-017-2029-0

Iizuka N, Miyamoto K, Okita K, Tangoku A, Hayashi H, Yosino S, Abe T, Morioka T, Hazama S, Oka M. Inhibitory effect of Coptidis Rhizoma and berberine on the proliferation of human esophageal cancer cell lines. Cancer Lett. 2000;148(1):19-25. https://doi.org/10.1016/s0304-3835(99)00264-5

Achi IT, Sarbadhikary P, George BP, Abrahamse H. Multi-target potential of berberine as an antineoplastic and antimetastatic agent: A special focus on lung cancer treatment. Cells. 2022;11(21):3433. https://doi.org/10.3390/cells11213433

Iizuka N, Oka M, Yamamoto K, Tangoku A, Miyamoto K, Miyamoto T, Uchimura S, Hamamoto Y, Okita K. Identification of common or distinct genes related to antitumor activities of a medicinal herb and its major component by oligonucleotide microarray. Int J Cancer. 2003;107(4):666-72. https://doi.org/10.1002/ijc.11452

Park SH, Sung JH, Kim EJ, Chung N. Berberine induces apoptosis via ROS generation in PANC-1 and MIA-PaCa2 pancreatic cell lines. Braz J Med Biol Res. 2015;48(2):111-9. https://doi.org/10.1590/1414-431X20144293

Liu B, Fu XQ, Li T, Su T, Guo H, Zhu PL, Tse AK, Liu SM, Yu ZL. Computational and experimental prediction of molecules involved in the anti-melanoma action of berberine. J Ethnopharmacol. 2017;208:225-35. https://doi.org/10.1016/j.jep.2017.07.023

Kou Y, Li L, Li H, Tan Y, Li B, Wang K, Du B. Berberine suppressed epithelial mesenchymal transition through cross-talk regulation of PI3K/AKT and RARα/RARβ in melanoma cells. Biochem Biophys Res Commun. 2016;479(2):290-6. https://doi.org/10.1016/j.bbrc.2016.09.061

Wang N, Feng Y, Lau EP, Tsang C, Ching Y, Man K, Tong Y, Nagamatsu T, Su W, Tsao S. F-actin reorganization and inactivation of rho signaling pathway involved in the inhibitory effect of Coptidis Rhizoma on hepatoma cell migration. Integr Cancer Ther. 2010;9(4):354-64. https://doi.org/10.1177/1534735410379121

Zhu T, Li LL, Xiao GF, Luo QZ, Liu QZ, Yao KT, Xiao GH. Berberine increases doxorubicin sensitivity by suppressing STAT3 in lung cancer. Am J Chin Med. 2015;43(7):1487-502. https://doi.org/10.1142/S0192415X15500846

Kalathil D, John S, Nair AS. FOXM1 and cancer: Faulty cellular signaling derails homeostasis. Front Oncol. 2021;10:626836. https://doi.org/10.3389/fonc.2020.626836

Wang X, Quail E, Hung NJ, Tan Y, Ye H, Costa RH. Increased levels of forkhead box M1B transcription factor in transgenic mouse hepatocytes prevent age-related proliferation defects in regenerating liver. Proc Natl Acad Sci U S A. 2001;98(20):11468-73. https://doi.org/10.1073/pnas.201360898

Tchakarska G, Sola B. The double dealing of cyclin D1. Cell Cycle. 2020;19(2):163-78. https://doi.org/10.1080/15384101.2019.1706903

Wierstra I, Alves J. FOXM1c transactivates the human c-Myc promoter directly via the two TATA boxes P1 and P2. FEBS J. 2006;273(20):4645-67. https://doi.org/10.1111/j.1742-4658.2006.05468.x

Tang JH, Yang L, Chen JX, Li QR, Zhu LR, Xu QF, Huang GH, Zhang ZX, Xiang Y, Du L, Zhou Z, Lv SQ. Bortezomib inhibits growth and sensitizes glioma to temozolomide (TMZ) via down-regulating the FOXM1-Survivin axis. Cancer Commun (Lond). 2019;39(1):81. https://doi.org/10.1186/s40880-019-0424-2

Pelengaris S, Khan M. The many faces of c-MYC. Arch Biochem Biophys. 2003;416(2):129-36. https://doi.org/10.1016/s0003-9861(03)00294-7

Dhanasekaran R, Deutzmann A, Mahauad-Fernandez WD, Hansen AS, Gouw AM, Felsher DW. The MYC oncogene - the grand orchestrator of cancer growth and immune evasion. Nat Rev Clin Oncol. 2022;19(1):23-36. https://doi.org/10.1038/s41571-021-00549-2

Shojaei F, Yazdani-Nafchi F, Banitalebi-Dehkordi M, Chehelgerdi M, Khorramian-Ghahfarokhi M. Trace of survivin in cancer. Eur J Cancer Prev. 2019;28(4):365-72. https://doi.org/10.1097/CEJ.0000000000000453

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Published

2025-06-26

How to Cite

1.
Jeong JH, Lee HJ. Antitumor activity of Coptis chinensis rhizome extract against PANC-1 cells. Arch Biol Sci [Internet]. 2025Jun.26 [cited 2025Aug.27];77(2):197-20. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/10977

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