Skip to main content
Log in

Lacticaseibacillus casei LH23 Suppressed HPV Gene Expression and Inhibited Cervical Cancer Cells

  • Published:
Probiotics and Antimicrobial Proteins Aims and scope Submit manuscript

Abstract

Microbiota of lower female reproductive tract is special in its microorganism composition with Lactobacillus as the predominant bacteria. A few of Lactobacillus species have been identified to benefit the inhibition of inflammatory and malignant diseases. Lacticaseibacillus casei LH23 is a strain isolated from traditional fermented food and had been demonstrate to ameliorate DSS-induced colitis in mice. In the present study, effects of Lacticaseibacillus casei LH23 on cervical cancer cells were investigated. Supernatants of lysates and heat-inactivated Lacticaseibacillus casei LH23 were found to inhibit the expression of human papillomavirus genes E6/E7 which is the main causative factor of cervical cancer. With MTT, EdU staining, and TUNEL staining assays, Lacticaseibacillus casei LH23 was shown to suppress the proliferation and induced the apoptosis of cervical cancer cells. Additionally, with wound-healing and Western-blot assays, Lacticaseibacillus casei LH23 was shown to slowdown the migration of cervical cancer cells and altered the expression of metastasis-related genes. These results demonstrated the anti-cervical cancer potential of Lacticaseibacillus casei LH23.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Availability of Data and Material

All data generated during this study are included in this published article. Materials are available upon reasonable request.

Abbreviations

HPV:

Human papillomavirus

LAB :

Lactic acid bacteria

EMT:

Epithelial to mesenchymal transition

References

  1. Crosbie EJ, Einstein MH, Franceschi S, Kitchener HC (2013) Human papillomavirus and cervical cancer. Lancet 382(9895):889–899. https://doi.org/10.1016/S0140-6736(13)60022-7

    Article  PubMed  Google Scholar 

  2. Hoppe-Seyler K, Bossler F, Braun JA, Herrmann AL, Hoppe-Seyler F (2018) The HPV E6/E7 oncogenes: key factors for viral carcinogenesis and therapeutic targets. Trends Microbiol 26(2):158–168. https://doi.org/10.1016/j.tim.2017.07.007

    Article  CAS  PubMed  Google Scholar 

  3. Wise-Draper TM, Wells SI (2008) Papillomavirus E6 and E7 proteins and their cellular targets. Front Biosci 13:1003–1017. https://doi.org/10.2741/2739

    Article  CAS  PubMed  Google Scholar 

  4. He H, Lai Y, Hao Y et al (2017) Selective p300 inhibitor C646 inhibited HPV E6–E7 genes, altered glucose metabolism and induced apoptosis in cervical cancer cells. Eur J Pharmacol 812:206–215. https://doi.org/10.1016/j.ejphar.2017.06.005

    Article  CAS  PubMed  Google Scholar 

  5. Gao X, Jin Z, Tan X et al (2020) Hyperbranched poly(beta-amino ester) based polyplex nanopaticles for delivery of CRISPR/Cas9 system and treatment of HPV infection associated cervical cancer. J Control Release 321:654–668. https://doi.org/10.1016/j.jconrel.2020.02.045

    Article  CAS  PubMed  Google Scholar 

  6. Zhen S, Lu J, Liu YH, Chen W, Li X (2020) Synergistic antitumor effect on cervical cancer by rational combination of PD1 blockade and CRISPR-Cas9-mediated HPV knockout. Cancer Gene Ther 27(3–4):168–178. https://doi.org/10.1038/s41417-019-0131-9

    Article  CAS  PubMed  Google Scholar 

  7. Norenhag J, Du J, Olovsson M, Verstraelen H, Engstrand L, Brusselaers N (2020) The vaginal microbiota, human papillomavirus and cervical dysplasia: a systematic review and network meta-analysis. BJOG 127(2):171–180. https://doi.org/10.1111/1471-0528.15854

    Article  CAS  PubMed  Google Scholar 

  8. Mitra A, MacIntyre DA, Marchesi JR, Lee YS, Bennett PR, Kyrgiou M (2016) The vaginal microbiota, human papillomavirus infection and cervical intraepithelial neoplasia: what do we know and where are we going next? Microbiome 4(1):58. https://doi.org/10.1186/s40168-016-0203-0

    Article  PubMed  PubMed Central  Google Scholar 

  9. Petrova MI, Lievens E, Malik S, Imholz N, Lebeer S (2015) Lactobacillus species as biomarkers and agents that can promote various aspects of vaginal health. Front Physiol 6:81. https://doi.org/10.3389/fphys.2015.00081

    Article  PubMed  PubMed Central  Google Scholar 

  10. Usyk M, Zolnik CP, Castle PE et al (2020) Cervicovaginal microbiome and natural history of HPV in a longitudinal study. PLoS Pathog 16(3):e1008376. https://doi.org/10.1371/journal.ppat.1008376

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen Y, Qiu X, Wang W et al (2020) Human papillomavirus infection and cervical intraepithelial neoplasia progression are associated with increased vaginal microbiome diversity in a Chinese cohort. BMC Infect Dis 20(1):629. https://doi.org/10.1186/s12879-020-05324-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Mitra A, MacIntyre DA, Lee YS et al (2015) Cervical intraepithelial neoplasia disease progression is associated with increased vaginal microbiome diversity. Sci Rep 5:16865. https://doi.org/10.1038/srep16865

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Mitra A, MacIntyre DA, Ntritsos G et al (2020) The vaginal microbiota associates with the regression of untreated cervical intraepithelial neoplasia 2 lesions. Nat Commun 11(1):1999. https://doi.org/10.1038/s41467-020-15856-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Wang KD, Xu DJ, Wang BY, Yan DH, Lv Z, Su JR (2018) Inhibitory effect of vaginal lactobacillus supernatants on cervical cancer cells. Probiotics Antimicrob Proteins 10(2):236–242. https://doi.org/10.1007/s12602-017-9339-x

    Article  PubMed  Google Scholar 

  15. Riaz Rajoka MS, Zhao H, Lu Y et al (2018) Anticancer potential against cervix cancer (HeLa) cell line of probiotic Lactobacillus casei and Lactobacillus paracasei strains isolated from human breast milk. Food Funct 9(5):2705–2715. https://doi.org/10.1039/c8fo00547h

    Article  CAS  PubMed  Google Scholar 

  16. Łaniewski P, Ilhan ZE, Herbst-Kralovetz MM (2020) The microbiome and gynaecological cancer development, prevention and therapy. Nat Rev Urol 17(4):232–250. https://doi.org/10.1038/s41585-020-0286-z

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Koirala R, Gargari G, Arioli S et al (2020) Effect of oral consumption of capsules containing Lactobacillus paracasei LPC-S01 on the vaginal microbiota of healthy adult women: a randomized, placebo-controlled, double-blind crossover study. FEMS Microbiol Ecol 96(6):fiaa084. https://doi.org/10.1093/femsec/fiaa084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Laue C, Papazova E, Liesegang A et al (2018) Effect of a yoghurt drink containing Lactobacillus strains on bacterial vaginosis in women — a double-blind, randomised, controlled clinical pilot trial. Benef Microbes 9(1):35–50. https://doi.org/10.3920/BM2017.0018

    Article  CAS  PubMed  Google Scholar 

  19. Liu M, Ding J, Zhang H et al (2020) Lactobacillus casei LH23 modulates the immune response and ameliorates DSS-induced colitis via suppressing JNK/p-38 signal pathways and enhancing histone H3K9 acetylation. Food Funct 11(6):5473–5485. https://doi.org/10.1039/d0fo00546k

    Article  CAS  PubMed  Google Scholar 

  20. Lai Y, He Z, Zhang A et al (2020) Tip60 and p300 function antagonistically in the epigenetic regulation of HPV18 E6/E7 genes in cervical cancer HeLa cells. Genes Genomics 42(6):691–698. https://doi.org/10.1007/s13258-020-00938-4

    Article  CAS  PubMed  Google Scholar 

  21. Nami Y, Abdullah N, Haghshenas B, Radiah D, Rosli R, Khosroushahi AY (2014) Assessment of probiotic potential and anticancer activity of newly isolated vaginal bacterium Lactobacillus plantarum 5BL. Microbiol Immunol 58(9):492–502. https://doi.org/10.1111/1348-0421.12175

    Article  CAS  PubMed  Google Scholar 

  22. Górska A, Przystupski D, Niemczura MJ, Kulbacka J (2019) Probiotic bacteria: a promising tool in cancer prevention and therapy. Curr Microbiol 76(8):939–949. https://doi.org/10.1007/s00284-019-01679-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Jahanshahi M, Maleki Dana P, Badehnoosh B et al (2020) Anti-tumor activities of probiotics in cervical cancer. J Ovarian Res 13(1):68. https://doi.org/10.1186/s13048-020-00668-x

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sungur T, Aslim B, Karaaslan C, Aktas B (2017) Impact of exopolysaccharides (EPSs) of Lactobacillus gasseri strains isolated from human vagina on cervical tumor cells (HeLa). Anaerobe 47:137–144. https://doi.org/10.1016/j.anaerobe.2017.05.013

    Article  PubMed  Google Scholar 

  25. Wang H, Cheng X, Zhang L, Xu S, Zhang Q, Lu RA (2019) A surface-layer protein from Lactobacillus acidophilus NCFM induces autophagic death in HCT116 cells requiring ROS-mediated modulation of mTOR and JNK signaling pathways. Food Funct 10(7):4102–4112. https://doi.org/10.1039/c9fo00109c

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This work was supported by the National Key R & D Program of China (2017YFD0400304) and the Natural Science Foundation of Tianjin (18JCYBJC91500).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Hongpeng He.

Ethics declarations

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, S., Hao, Y., Zhang, X. et al. Lacticaseibacillus casei LH23 Suppressed HPV Gene Expression and Inhibited Cervical Cancer Cells. Probiotics & Antimicro. Prot. 15, 443–450 (2023). https://doi.org/10.1007/s12602-021-09848-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12602-021-09848-7

Keywords

Navigation