Journal of Animal Reproduction and Biotechnology (한국동물생명공학회지)

The Korean Society of Animal Reproduction and Biotechnology (한국동물생명공학회)
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Anticancer activity of ginsenosides Rh2 on various cancer cells

  • Received : 2023.09.11
  • Accepted : 2023.09.16
  • Published : 2023.09.30
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Abstract

Background: This study has mainly focused on finding pharmacological effects of ginsenosides that can reduce the unwanted side effects of the cytotoxic anticancer drugs and are highly effective on prostate cancer, colorectal cancer, liver cancer, hormone-dependent breast cancer, triple-negative breast cancer, and brain cancer (neuroblastoma). Methods: Minor and rare ginsenosides (GS) of Rh2 which have a high absorption ability and excellent pharmacological actions were treated with the 6 different types of cancer cell lines and their anticancer activities were investigated by analyzing gene expressions associated with various cancers through qPCR and other relevant methods. Results: In cancer cells exposed to Rh2, cell viability and cell migration were reduced, and apoptosis was induced. Each cancer cell was divided into three groups according to the cell proliferation response by Rh2; 1) A group in which the cell viability decreases inversely to an increase in Rh2 treatment concentration; 2) A group in which the cell viability rapidly decreases in Rh2 treatment above a certain level of concentration; 3) A group in which the cell viability was not suppressed below 20-30% even with 100 μL of Rh2, the highest concentration used in this study. Conclusions: It was shown that Rh2 has a significant effect on inhibiting the proliferation of prostate cancer cells and hormone-dependent breast cancer cells.

Keywords

Acknowledgement

We appreciate Dr. W.T. Im's lab for providing ginsenosides Rh2 as a raw material for this study.

References

  1. Chen Y, Zhang Y, Song W, Zhang Y, Dong X, Tan M. 2019. Ginsenoside Rh2 inhibits migration of lung cancer cells under hypoxia via mir-491. Anticancer Agents Med. Chem. 19: 1633-1641. https://doi.org/10.2174/1871520619666190704165205
  2. Choi WY, Lim HW, Lim CJ. 2013. Anti-inflammatory, antioxidative and matrix metalloproteinase inhibitory properties of 20(R)-ginsenoside Rh2 in cultured macrophages and keratinocytes. J. Pharm. Pharmacol. 65:310-316. https://doi.org/10.1111/j.2042-7158.2012.01598.x
  3. Christensen LP. 2009. Ginsenosides: chemistry, biosynthesis, analysis, and potential health effects. Adv. Food Nutr. Res. 55:1-99.
  4. Fukami H, Ueda T, Matsuoka N. 2019. Pharmacokinetic study of compound K in Japanese subjects after ingestion of Panax ginseng fermented by Lactobacillus paracasei A221 reveals significant increase of absorption into blood. J. Med. Food 22:257-263. https://doi.org/10.1089/jmf.2018.4271
  5. Han S, Jeong AJ, Yang H, Kang KB, Lee H, Yi EH, Kim BH, Cho CH, Chung JW, Sung SH, Ye SK. 2016. Ginsenoside 20(S)-Rh2 exerts anti-cancer activity through targeting IL-6-induced JAK2/STAT3 pathway in human colorectal cancer cells. J. Ethnopharmacol. 194:83-90. https://doi.org/10.1016/j.jep.2016.08.039
  6. Hou J, Xue J, Lee M, Liu L, Zhang D, Sun M, Zheng Y, Sung C. 2013. Ginsenoside Rh2 improves learning and memory in mice. J. Med. Food 16:772-776. https://doi.org/10.1089/jmf.2012.2564
  7. Jin S, Jeon JH, Lee S, Kang WY, Seong SJ, Yoon YR, Choi MK, Song IS. 2019. Detection of 13 ginsenosides (Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rh2, F1, compound K, 20(S)-protopanaxadiol, and 20(S)-protopanaxatriol) in human plasma and application of the analytical method to human pharmacokinetic studies following two week-repeated administration of red ginseng extract. Molecules 24:2618.
  8. Kim DH. 2018. Gut microbiota-mediated pharmacokinetics of ginseng saponins. J. Ginseng Res. 42:255-263. https://doi.org/10.1016/j.jgr.2017.04.011
  9. Kim JH and Choi JS. 2016. Effect of ginsenoside Rh-2 via activation of caspase-3 and Bcl-2-insensitive pathway in ovarian cancer cells. Physiol. Res. 65:1031-1037. https://doi.org/10.33549/physiolres.933367
  10. Kim SH, Jung NH, Oh MG, Yoon JT. 2020. Study on the VEGF gene expression and the role of PMSG hormone in the development of endometrial cancer in mice. J. Anim. Reprod. Biotechnol. 35:35-41. https://doi.org/10.12750/JARB.35.1.35
  11. Lee H, Lee S, Jeong D, Kim SJ. 2018. Ginsenoside Rh2 epigenetically regulates cell-mediated immune pathway to inhibit proliferation of MCF-7 breast cancer cells. J. Ginseng Res. 42:455-462. https://doi.org/10.1016/j.jgr.2017.05.003
  12. Li H, Huang N, Zhu W, Wu J, Yang X, Teng W, Tian J, Fang Z, Luo Y, Chen M, Li Y. 2018. Modulation the crosstalk between tumor-associated macrophages and non-small cell lung cancer to inhibit tumor migration and invasion by ginsenoside Rh2. BMC Cancer 18:579.
  13. Lim WT. 2011. Development of biotransformation technique for the production of single minor ginsenoside and bioconversion of medicinal herbs' saponins using the recombinant ginsenosidase clone libraries. Korea Advanced Institute of Science and Technology. https://scienceon.kisti.re.kr/commons/util/originalView.do?cn=TRKO201200002445&dbt=TRKO&rn=
  14. Ministry of Health and Welfare of South Korea. 2021. Cancer survival rate increased to 70.7%, and the incidence of breast cancer and prostate cancer is on the rise. press release. 2021-12-29. http://www.mohw.go.kr/react/al/sal0301vw.jsp?PAR_MENU_ID=04&MENU_ID=0403&CONT_SEQ=369164&page=1
  15. Park H. 2019. The role of gut microbiota in ginsenoside metab-olism and biotransformation of ginsenoside by lactic acid bacteria. Curr. Top. Lact. Acid Bact. Probiotics 5:1-12. https://doi.org/10.35732/ctlabp.2019.5.1.1
  16. Peng K, Luo T, Li J, Huang J, Dong Z, Liu J, Pi C, Zou Z, Gu Q, Liu O, Zhang JT, Luo ZY. 2022. Ginsenoside Rh2 inhibits breast cancer cell growth via ERβ-TNFα pathway. Acta Biochim. Biophys. Sin. (Shanghai) 54:647-656. https://doi.org/10.3724/abbs.2022039
  17. Qian J, Li J, Jia JG, Jin X, Yu DJ, Guo CX, Xie B, Qian LY. 2016. Ginsenoside-Rh2 inhibits proliferation and induces apoptosis of human gastric cancer SGC-7901 side population cells. Asian Pac. J. Cancer Prev. 17:1817-1821. https://doi.org/10.7314/APJCP.2016.17.4.1817
  18. Qian Y, Huang R, Li S, Xie R, Qian B, Zhang Z, Li L, Wang B, Tian C, Yang J, Xiang M. 2019. Ginsenoside Rh2 reverses cyclophosphamide-induced immune deficiency by regulating fatty acid metabolism. J. Leukoc. Biol. 106:1089-1100. https://doi.org/10.1002/JLB.2A0419-117R
  19. Ratan ZA, Haidere MF, Hong YH, Park SH, Lee JO, Lee J, Cho JY. 2021. Pharmacological potential of ginseng and its major component ginsenosides. J. Ginseng Res. 45:199-210. https://doi.org/10.1016/j.jgr.2020.02.004
  20. Shi X, Yang J, Wei G. 2018. Ginsenoside 20(S)-Rh2 exerts anticancer activity through the Akt/GSK3β signaling pathway in human cervical cancer cells. Mol. Med. Rep. 17:4811-4816.
  21. Tang XP, Tang GD, Fang CY, Liang ZH, Zhang LY. 2013. Effects of ginsenoside Rh2 on growth and migration of pancreatic cancer cells. World J. Gastroenterol. 19:1582-1592. https://doi.org/10.3748/wjg.v19.i10.1582
  22. Tong-Lin Wu T, Tong YC, Chen IH, Niu HS, Li Y, Cheng JT. 2018. Induction of apoptosis in prostate cancer by ginsenoside Rh2. Oncotarget 9:11109-11118. https://doi.org/10.18632/oncotarget.24326
  23. Xia T, Wang YN, Zhou CX, Wu LM, Liu Y, Zeng QH, Zhang XL, Yao JH, Wang M, Fang JP. 2017. Ginsenoside Rh2 and Rg3 inhibit cell proliferation and induce apoptosis by increasing mitochondrial reactive oxygen species in human leukemia Jurkat cells. Mol. Med. Rep. 15:3591-3598. https://doi.org/10.3892/mmr.2017.6459
  24. Yang J, Yuan D, Xing T, Su H, Zhang S, Wen J, Bai Q, Dang D. 2016. Ginsenoside Rh2 inhibiting HCT116 colon cancer cell proliferation through blocking PDZ-binding kinase/T-LAK cell-originated protein kinase. J. Ginseng Res. 40:400-408. https://doi.org/10.1016/j.jgr.2016.03.007
  25. Yang Y, Liu X, Li S, Chen Y, Zhao Y, Wei Y, Qiu Y, Liu Y, Zhou Z, Han J, Wu G, Ding Q. 2020. Genome-scale CRISPR screening for potential targets of ginsenoside compound K. Cell Death Dis. 11:39.
  26. Zhang H, Park S, Huang H, Kim E, Yi J, Choi SK, Ryoo Z, Kim M. 2021. Anticancer effects and potential mechanisms of ginsenoside Rh2 in various cancer types (Review). Oncol. Rep. 45:33.