Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
권호 표지
DOI QR코드

DOI QR Code

Ginsenoside Rk1 inhibits HeLa cell proliferation through an endoplasmic reticulum signaling pathway

  • Qiuyang Li (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Hang Sun (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Shiwei Liu (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Jinxin Tang (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Shengnan Liu (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Pei Yin (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Qianwen Mi (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Jingsheng Liu (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Lei yu (College of Food Science and Engineering, Jilin Agricultural University) ;
  • Yunfeng Bi (College of Food Science and Engineering, Jilin Agricultural University)
  • Received : 2022.05.12
  • Accepted : 2023.04.08
  • Published : 2023.09.01
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Changes to work-life balance has increased the incidence of cervical cancer among younger people. A minor ginseng saponin known as ginsenoside Rk1 can inhibit the growth and survival of human cancer cells; however, whether ginsenoside Rk1 inhibits HeLa cell proliferation is unknown. Methods and results: Ginsenoside Rk1 blocked HeLa cells in the G0/G1 phase in a dose-dependent manner and inhibited cell division and proliferation. Ginsenoside Rk1 markedly also activated the apoptotic signaling pathway via caspase 3, PARP, and caspase 6. In addition, ginsenoside Rk1 increased LC3B protein expression, indicating the promotion of the autophagy signaling pathway. Protein processing in the endoplasmic reticulum signaling pathway was downregulated in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, consistent with teal-time quantitative PCR and western blotting that showed YOD1, HSPA4L, DNAJC3, and HSP90AA1 expression levels were dramatically decreased in HeLa cells treated with ginsenoside Rk1, with YOD1 was the most significantly inhibited by ginsenoside Rk1 treatment. Conclusion: These findings indicate that the toxicity of ginsenoside Rk1 in HeLa cells can be explained by the inhibition of protein synthesis in the endoplasmic reticulum and enhanced apoptosis, with YOD1 acting as a potential target for cervical cancer treatment.

Keywords

Acknowledgement

This work was partly supported by Science and Technology Department of Jilin Province, China, for providing financial support (20210204179YY ).

References

  1. Satari M, Javani JF, Abolmaleki P, Soleimani H. Influence of static magnetic field on HeLa and Huo2 cells in the presence of aloe vera extract. Asian Pac J Cancer Prev 2021;22(S1):9e15. https://doi.org/10.31557/APJCP.2021.22.S1.9.
  2. Mata Rocha M, Rodriguez Hernandez RM, Chavez Olmos P, Garrido E, Romero Tlalolini M. Presence of HPV DNA in extracellular vesicles from HeLa cells and cervical samples. Enferm Infecc Microbiol Clin (Engl Ed) 2020;38(4):159 165. https://doi.org/10.1016/j.eimc.2019.06.011.
  3. Bhatia R, Vyas A, El-Bahy SM. Rationale design, synthesis, pharmacological and in-silico investigation of indole-functionalized isoxazoles as antiinflammatory agents. Chemistry Select 2022;(26):1e10. https://doi.org/10.1002/slct.202200800.
  4. Jin S, Bang S, Ahn MA, Lee K, Kim k, Hyun TK, et al. Overproduction of anthocyanin in ginseng hairy roots enhances their antioxidant, antimicrobial, and anti-elastase activities. Kor Soc Plant Biotechnol 2021;(2). https://doi.org/10.5010/JPB.2021.48.2.100.
  5. Peng ZX, Gong XB, Yang Y, Huang LG, Zhang QY, Zhang P, Wan RZ, Zhang BS. Hepatoprotective effect of quercetin against LPS/d GalN induced acute liver injury in mice by inhibiting the IKK/NF kappaB and MAPK signal pathways. Int Immunopharmacol 2017;52:281e9. https://doi.org/10.1016/j.intimp.2017.09.022.
  6. Li S, Wang P, Yang W, Zhao C, Xu H, et al. Characterization of the components and pharmacological effects of mountain-cultivated ginseng and garden ginseng based on the integrative pharmacology strategy. Front Pharmacol 2021;12:659954. https://doi.org/10.3389/fphar.2021.659954.
  7. Samartzi F, Theodosiadou EK, Vainas E, Saratsi A, Tsiligianni T, Rekkas CA, et al. Plasminogen activator activity and plasminogen activator inhibition in the uterus of ewes after the induction of oestrus synchronization or superovulation, involving eCG. Small Rumin Res 2022;210. https://doi.org/10.1016/j.smallrumres.2022.106672.
  8. Sebestyen E, Singh B, Minana B, AmadisA, Francesca P, Mateo. Corrigendum: large scale analysis of genome and transcriptome alterations in multiple tumors unveils novel cancer relevant splicing networks. Genome Res 2018;28(9):1426. https://doi.org/10.1101/gr.242214.118.
  9. Pandey P, Khan F, Farhan M, Jafri A, et al. Elucidation of Rutin role in inducing caspase dependent apoptosis via HPV-E6 and E7 downregulation in cervical cancer HeLa cells. Biosci Rep 2021;41(6). https://doi.org/10.1042/BSR20210670.
  10. Bi YF, Li QY, Tao WM, Tang JX, You GF, Yu L. Ginsenoside Rg1 and ginsenoside Rh1 prevent liver injury induced by acetaminophen in mice. J Food Biochem 2021:e13816. https://doi.org/10.1111/jfbc.13816.
  11. Zarrinnahad H, Mahmoodzadeh A, Hamidi MP, Mahdavi M, Moradi A, Bagheri KP, Shahbazzadeh D. Apoptotic effect of melittin purified from Iranian honey bee venom on human cervical cancer HeLa cell line. Int J Pept Res Ther 2018;24(4):563 570. https://doi.org/10.1007/s1098901796411.
  12. Qin G, Li P, Xue Z. Effect of allyl isothiocyanate on the viability and apoptosis of the human cervical cancer HeLa cell line in vitro. Oncol Lett 2018;15(6):8756e60. https://doi.org/10.3892/ol.2018.8428.
  13. Bian S, Liu M, Yang S, Lu S, Wang S, Bai X, Zhao D, Wang J. 20(S) Ginsenoside Rh2 induced apoptosis and protective autophagy in cervical cancer cells by inhibiting AMPK/mTOR pathway. Biosci Biotechnol Biochem 2021;86(1):92e103. https://doi.org/10.1093/bbb/zbab189.
  14. Song L, Yang F, Wang Z, Zhou Y. Ginsenoside Rg5 inhibits cancer cell migration by inhibiting the nuclear factor kappaB and erythropoietin producing hepatocellular receptor A2 signaling pathways. Oncol Lett 2021;21(6):452. https://doi.org/10.3892/ol.2021.12713.
  15. Xu W, Zhang Q, Ding C, Sun HY, Cao LJ. Gasdermin E derived caspase 3 inhibitors effectively protect mice from acute hepatic failure. Acta Pharmacologica Sinica 2020;42(1). https://doi.org/10.1038/s4140102004342.
  16. Sun Y, Wu J, Dong X, Zhang J, Liu G. MicroRNA 506 3p increases the response to PARP inhibitors and cisplatin by targeting EZH2/beta catenin in serous ovarian cancers. Transl Oncol 2021;14(2):100987. https://doi.org/10.1016/j.tranon.2020.100987.
  17. Li F, Tang X, Xu Y, Wang C, Wang L. A dual protein cascade reaction for the regioselective synthesis of quinoxalines. Org Lett 2020;22(10):3900e4. https://doi.org/10.1021/acs.orglett.0c01186.
  18. Jacomin AC, Petridi S, Di Monaco M, Zambarlal B, Ashish J, Mulakkal NC, Anthimi P, Powell EL, Bonita C, Cleidiane Z. Regulation of expression of autophagy genes by Atg8a interacting partners sequoia, YL 1, and Sir2 in Drosophila. Cell Rep 2020;31(8):107695. https://doi.org/10.1016/j.celrep.2020.107695.
  19. Lee YW, Chen M, Chung IF, Chang TY. lncExplore: a database of pan cancer analysis and systematic functional annotation for lncRNAs from RNA sequencing data. Database (Oxford) 2021. https://doi.org/10.1093/database/baab053.
  20. Zhou B, Lu D, Wang A, Cui J, Zhang L, Li J, Fan L, Wei W, Liu J, Sun G. Endoplasmic reticulum stress promotes sorafenib resistance via miR 188 5p/ hnRNPA2B1 mediated upregulation of PKM2 in hepatocellular carcinoma. Mol Ther Nucleic Acids 2021;26:1051e65. https://doi.org/10.1016/j.omtn.2021.09.014.
  21. Yu Y, Wu D, Li Y, Hui Q, Zheng S. Ketamine enhances autophagy and endoplasmic reticulum stress in rats and SV HUC 1 cells via activating IRE1 TRAF2 ASK1 JNK pathway. Cell Cycle 2021;20(18):1907e22. https://doi.org/10.1080/15384101.2021.1966199.
  22. Liu K, Chen Y, Ai F, Li YQ, Zhang WT. PHLDA3 inhibition attenuates endoplasmic reticulum stress induced apoptosis in myocardial hypoxia/reoxygenation injury by activating the PI3K/AKT signaling pathway. Exp Ther Med 2021;21(6):613. https://doi.org/10.3892/etm.2021.10045.
  23. Dong JY, Xia KJ, Liang W, Liu LL, Chen DP. Ginsenoside Rb1 alleviates colitis in mice via activation of endoplasmic reticulum resident E3 ubiquitin ligase Hrd1 signaling pathway. Acta Pharmacol Sin 2021;42(9):1461 1471. https://doi.org/10.1038/s41401020005619.
  24. Yorifuji H, Arase N, Kohyama M, Hirano T, Suenaga T, Kumanogoh A, Arase H. Transport of cellular misfolded proteins to the cell surface by HLA B27 free heavy chain. Biochemical and Biophysical Research Communications 2019;511(4). https://doi.org/10.1016/j.bbrc.2019.02.120.
  25. Liu C, Huang S, Wang X, Huang S. The otubain YOD1 suppresses aggregation and activation of the signaling adaptor MAVS through Lys63 linked deubiquitination. J Immunol 2019;202(10):2957e70. https://doi.org/10.4049/jimmunol.1800656.
  26. Wang S, Mo Y, Midorikawa K, Zhang Z, Murata M. The potent tumor suppressor miR 497 inhibits cancer phenotypes in nasopharyngeal carcinoma by targeting ANLN and HSPA4L. Oncotarget 2015;6(34):35893e907. https://doi.org/10.18632/oncotarget.5651.
  27. Tang Y, Tang R, Tang M, Huang P, Nie S. LncRNA DNAJC3 AS1 regulates fatty acid synthase via the EGFR pathway to promote the progression of colorectal cancer. Front Oncol 2020;10:604534. https://doi.org/10.3389/fonc.2020.604534.
  28. Wan X, Zhu L, Zhao L, Peng L, Chen K. hPER3 promotes adipogenesis via hHSP90AA1 mediated inhibition of Notch1 pathway. Cell Death Dis 2021;12(4):301. https://doi.org/10.1038/s41419021035840.