Investigation of the protective and therapeutic effects of <i>Lactobacillus casei</i> and <i>Saccharomyces cerevisiae</i> in a breast cancer mouse model

Kholoud Baraka; Rania Abozahra; Maged Wasfy Helmy; Nada Salah El Dine El Meniawy; Sarah M Abdelhamid; Kholoud Baraka; Rania Abozahra; Maged Wasfy Helmy; Nada Salah El Dine El Meniawy; Sarah M Abdelhamid

doi:10.3934/microbiol.2022016

AIMS Microbiology

2022, Volume 8, Issue 2: 193-207. doi: 10.3934/microbiol.2022016

Previous Article Next Article

Research article Special Issues

Investigation of the protective and therapeutic effects of Lactobacillus casei and Saccharomyces cerevisiae in a breast cancer mouse model

1.
Microbiology and Immunology Department, Faculty of Pharmacy, Damanhour University, Damanhur, Egypt
2.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Damanhour University, Damanhur, Egypt

Received: 13 December 2021 Revised: 22 April 2022 Accepted: 27 April 2022 Published: 16 May 2022

Introduction
The development of novel strategies for cancer therapy is crucial to improve standard treatment protocols.

Aim
This study aimed to determine the protective and therapeutic effects of heat-killed preparations of Lactobacillus casei and Saccharomyces cerevisiae in a breast cancer mouse model.

Methods
Forty-two female BALB/c mice (7–8 weeks old) were divided into six groups (seven mice per group). Four groups were injected with 10⁷ Ehrlich ascites tumor (EAT) cells suspended in phosphate-buffered saline (PBS) subcutaneously into the left side of the mammary fat pad. Tumor growth was monitored weekly until all animals developed a palpable tumor. The tumor-bearing mice in the experimental groups received heat-killed L. casei or S. cerevisiae three times per week for 35 days. The mice in the control group received PBS. The remaining two groups received heated L. casei or S. cerevisiae and then were injected with EAT cells. After 35 days, all mice were sacrificed to determine the immune response.

Results
Animals that received heated S. cerevisiae exhibited the lowest rate of tumor growth compared with the other groups. TGF-β and IL-4 secretion was increased in all mice, whereas the secretion of INF-γ and IL-10 was decreased in breast tissues. Moreover, at the histopathological level, the volume of viable tumor in the control group was higher than in the treated groups.

Conclusion
Supplementary treatment with S. cerevisiae resulted in the best outcome in the breast cancer model compared with other treated and vaccinated groups.
- Lactobacillus casei,
- Saccharomyces cerevisiae,
- mouse,
- breast cancer,
- cytokines
Citation: Kholoud Baraka, Rania Abozahra, Maged Wasfy Helmy, Nada Salah El Dine El Meniawy, Sarah M Abdelhamid. Investigation of the protective and therapeutic effects of Lactobacillus casei and Saccharomyces cerevisiae in a breast cancer mouse model[J]. AIMS Microbiology, 2022, 8(2): 193-207. doi: 10.3934/microbiol.2022016

Related Papers:

Abstract

Introduction

The development of novel strategies for cancer therapy is crucial to improve standard treatment protocols.

Aim

This study aimed to determine the protective and therapeutic effects of heat-killed preparations of Lactobacillus casei and Saccharomyces cerevisiae in a breast cancer mouse model.

Methods

Forty-two female BALB/c mice (7–8 weeks old) were divided into six groups (seven mice per group). Four groups were injected with 10⁷ Ehrlich ascites tumor (EAT) cells suspended in phosphate-buffered saline (PBS) subcutaneously into the left side of the mammary fat pad. Tumor growth was monitored weekly until all animals developed a palpable tumor. The tumor-bearing mice in the experimental groups received heat-killed L. casei or S. cerevisiae three times per week for 35 days. The mice in the control group received PBS. The remaining two groups received heated L. casei or S. cerevisiae and then were injected with EAT cells. After 35 days, all mice were sacrificed to determine the immune response.

Results

Animals that received heated S. cerevisiae exhibited the lowest rate of tumor growth compared with the other groups. TGF-β and IL-4 secretion was increased in all mice, whereas the secretion of INF-γ and IL-10 was decreased in breast tissues. Moreover, at the histopathological level, the volume of viable tumor in the control group was higher than in the treated groups.

Conclusion

Supplementary treatment with S. cerevisiae resulted in the best outcome in the breast cancer model compared with other treated and vaccinated groups.

Author contributions

Sarah Abdelhamid and Rania Abozahra conceived and designed the study. Maged Wasfy and Nada Elmeniawy conducted the experiments. Sarah Abdelhamid and Kholoud Baraka analyzed the data. Kholoud Baraka wrote the manuscript. All authors read and approved the manuscript.

Conflict of interest

We declare that we have no conflict of interest.

Ethical approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. This research adhered to the accepted principles of ethical conduct according to the approval reference number (618PM5) by the Research Ethics Committee of the Faculty of Pharmacy, Damanhour University. Informed consent from the parents of young patients was obtained prior to undertaking testing and molecular investigation of their specimens.

Data availability

All data generated or analysed during this study are included in this published article.

Limitations of the study

Although EAT model is widely used for breast cancer assays, xenograft animal model of mammary glands using human cancer cell lines is still highly recommended to increase the reliability of results. In addition, development of more convenient vehicular methods for bacterial delivery is still highly recommended for future clinical applications.

References

[1]	Machaalani M, El Masri J, Ayoubi E Lm, et al. (2021) Cancer research activity in the Arab world: A 15-year bibliometric analysis. Res Square . https://doi.org/10.21203/rs.3.rs-389292/v1
[2]	World Health OrganizationGlobal Health Estimates 2016: Deaths by cause, age, sex, by country and by region, 2000–2016 (2018). Available from: https://www.who.int/data/global-health-estimates
[3]	Sung H, Ferlay J, Siegel RL, et al. (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA A Cancer J Clin 71: 209-249. https://doi.org/10.3322/caac.21660
[4]	Britt KL, Cuzick J, Phillips KA (2020) Key steps for effective breast cancer prevention. Nat Rev Cancer 20: 417-436. https://doi.org/10.1038/s41568-020-0266-x
[5]	Tran P, Lee SE, Kim DH, et al. (2020) Recent advances of nanotechnology for the delivery of anticancer drugs for breast cancer treatment. J Pharm Investig 50: 261-270. https://doi.org/10.1007/s40005-019-00459-7
[6]	Chakraborty C, Sharma AR, Sharma G, et al. (2020) The interplay among miRNAs, major cytokines, and cancer-related inflammation. Mol Ther Nucleic Acids 20: 606-620. https://doi.org/10.1016/j.omtn.2020.04.002
[7]	Martin-Hijano L, Sainz B (2020) The interactions between cancer stem cells and the innate interferon signaling pathway. Front Immunol 11: 526. https://doi.org/10.3389/fimmu.2020.00526
[8]	Aquino-López A, Senyukov VV, Vlasic Z, et al. (2017) Interferon gamma induces changes in natural killer (NK) cell ligand expression and alters NK cell-mediated lysis of pediatric cancer cell lines. Front Immunol 8: 391. https://doi.org/10.3389/fimmu.2017.00391
[9]	Zhou X, Wu X, Qin L, et al. (2020) Anti-breast cancer effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1,4-dione in vivo and in vitro through MAPK signaling pathway. Drug Des Dev Ther 14: 2667-2684. https://doi.org/10.2147/DDDT.S237699
[10]	Méndez Utz VE, Pérez Visñuk D, Perdigón G, et al. (2021) Milk fermented by Lactobacillus casei CRL431 administered as an immune adjuvant in models of breast cancer and metastasis under chemotherapy. Appl Microbiol Biotechnol 105: 327-340. https://doi.org/10.1007/s00253-020-11007-x
[11]	Lippitz BE (2013) Cytokine patterns in patients with cancer: a systematic review. Lancet Oncol 14: e218-e228. https://doi.org/10.1016/S1470-2045(12)70582-X
[12]	Glasgow E, Mishra L (2008) Transforming growth factor-β signaling and ubiquitinators in cancer. Endocr Relat Cancer 15: 59-72. https://doi.org/10.1677/ERC-07-0168
[13]	Tian M, Schiemann WP (2009) The TGF-β paradox in human cancer: an update. Future Oncol 5: 259-271. https://doi.org/10.2217/14796694.5.2.259
[14]	Aragón F, Carino S, Perdigón G, et al. (2014) The administration of milk fermented by the probiotic Lactobacillus casei CRL 431 exerts an immunomodulatory effect against a breast tumour in a mouse model. Immunobiology 219: 457-464. https://doi.org/10.1016/j.imbio.2014.02.005
[15]	Utz VE, Perdigón G, de LeBlanc AD (2017) Fermented milks and câncer. Dairy in human health and disease across the lifespan. New York: Academic Press 343-351. https://doi.org/10.1016/B978-0-12-809868-4.00026-1
[16]	Toumazi D, El Daccache S, Constantinou C (2021) An unexpected link: the role of mammary and gut microbiota on breast cancer development and management (Review). Oncol Rep 45: 1-5. https://doi.org/10.3892/or.2021.8031
[17]	Jafari S, Froushani SMA, Tokmachi A (2017) Combined extract of heated 4T1 and a heat-killed preparation of Lactobacillus casei in a mouse model of breast cancer. Iran J Med Sci 42: 457-464. Available from: https://pubmed.ncbi.nlm.nih.gov/29234178/
[18]	Ghoneum M, Wang L, Agrawal S, et al. (2007) Yeast therapy for the treatment of breast cancer: a nude mice model study. In Vivo 21: 251-258. Available from: https://pubmed.ncbi.nlm.nih.gov/17436573/
[19]	Ghoneum M, Badr El-Din NK, Noaman E, et al. (2008) Saccharomyces cerevisiae, the Baker's Yeast, suppresses the growth of Ehrlich carcinoma-bearing mice. Cancer Immunol Immunother 57: 581-592. https://doi.org/10.1007/s00262-007-0398-9
[20]	Abellan-Pose R, Rodríguez-Évora M, Vicente S, et al. (2017) Biodistribution of radiolabeled polyglutamic acid and PEG-polyglutamic acid nanocapsules. Eur J Pharm Biopharm 112: 155-163. https://doi.org/10.1016/j.ejpb.2016.11.015
[21]	Elzoghby AO, Mostafa SK, Helmy MW, et al. (2017) Multi-reservoir phospholipid shell encapsulating protamine nanocapsules for co-delivery of letrozole and celecoxib in breast cancer therapy. Pharm Res 34: 1956-1969. https://doi.org/10.1007/s11095-017-2207-2
[22]	Hsu SM, Raine L, Fanger H (1981) A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol 75: 734-738. https://doi.org/10.1093/ajcp/75.5.734
[23]	AbdElhamid Ahmed S, Zayed Dina G, Helmy Maged W, et al. (2018) Lactoferrin-tagged quantum dots-based theranosticnanocapsules for combined COX-2 inhibitor/herbal therapy of breast Cancer.Nanomedicine (Lond). Nanomedicine 13. https://doi.org/10.2217/nnm-2018-0196
[24]	El-Lakany SA, Elgindy NA, Helmy MW, et al. (2018) Elzoghby Lactoferrin-decorated vs. PEGylatedzeinnanospheres for combined aromatase inhibitor and herbal therapy of breast cancer. Expert Opin Drug Deliv 15: 835-850. https://doi.org/10.1080/17425247.2018.1505858
[25]	Helmy MM, Helmy MW, El-Mas MM (2015) Additive renoprotection by pioglitazone and fenofibrate against inflammatory, oxidative and apoptotic manifestations of cisplatin nephrotoxicity: modulation by PPARs. PLoS One 10: e0142303. https://doi.org/10.1371/journal.pone.0142303
[26]	Pengkumsri N, Sivamaruthi BS, Sirilun S, et al. (2017) Extraction of β-glucan from Saccharomyces cerevisiae: comparison of different extraction methods and in vivo assessment of immunomodulatory effect in mice. Food Sci Technol 37: 124-130. https://doi.org/10.1590/1678-457x.10716
[27]	Tiptiri-Kourpeti A, Spyridopoulou K, Santarmaki V, et al. (2016) Lactobacillus casei exerts anti-proliferative effects accompanied by apoptotic cell death and up-regulation of TRAIL in colon carcinoma cells. PLoS One 11: e0147960. https://doi.org/10.1371/journal.pone.0147960
[28]	Aindelis G, Chlichlia K (2020) Modulation of anti-tumour immune responses by probiotic bacteria. Vaccines 8: 329. https://doi.org/10.3390/vaccines8020329
[29]	Aindelis G, Tiptiri-Kourpeti A, Lampri E, et al. (2020) Immune responses raised in an experimental colon carcinoma model following oral administration of Lactobacillus casei. cancers (Basel) 12: 368. https://doi.org/10.3390/cancers12020368
[30]	Rahim SS, Khan N, Boddupalli CS, et al. (2005) Interleukin-10 (IL-10) mediated suppression of IL-12 production in RAW 264.7 cells also involves c-rel transcription factor. Immunology 114: 313-321. https://doi.org/10.1111/j.1365-2567.2005.02107.x
[31]	Mahmoud Amer E, Saber SH, Abo Markeb A, et al. (2021) Enhancement of β-glucan biological activity using a modified acid-base extraction method from Saccharomyces cerevisiae. Molecules 26: 2113. https://doi.org/10.3390/molecules26082113
[32]	Shen L, Li J, Liu Q, et al. (2018) Local blockade of interleukin 10 and CXC motif chemokine ligand 12 with nano-delivery promotes antitumor response in murine cancers. ACS Nano 12: 9830-9841. https://doi.org/10.1021/acsnano.8b00967
[33]	Guruprasath P, Kim J, Gunassekaran GR, et al. (2017) Interleukin-4 receptor-targeted delivery of Bcl-xL siRNA sensitizes tumors to chemotherapy and inhibits tumor growth. Biomaterials 142: 101-111. https://doi.org/10.1016/j.biomaterials.2017.07.024
[34]	Yan X, Jiao SC, Zhang GQ, et al. (2017) Tumor-associated immune factors are associated with recurrence and metastasis in non-small cell lung cancer. Cancer Gene Ther 24: 57-63. https://doi.org/10.1038/cgt.2016.40
[35]	Chen SM, Chieng WW, Huang SW, et al. (2020) The synergistic tumor growth-inhibitory effect of probiotic Lactobacillus on transgenic mouse model of pancreatic cancer treated with gemcitabine. Sci Rep 10: 20319. https://doi.org/10.1038/s41598-020-77322-5

Reader Comments

Your name:*

Email:*
© 2022 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)