Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2022 Aug 27;10(9):1733.
doi: 10.3390/microorganisms10091733.

Do Bacteria Provide an Alternative to Cancer Treatment and What Role Does Lactic Acid Bacteria Play?

Affiliations
Review

Do Bacteria Provide an Alternative to Cancer Treatment and What Role Does Lactic Acid Bacteria Play?

Leon M T Dicks et al. Microorganisms. .

Abstract

Cancer is one of the leading causes of mortality and morbidity worldwide. According to 2022 statistics from the World Health Organization (WHO), close to 10 million deaths have been reported in 2020 and it is estimated that the number of cancer cases world-wide could increase to 21.6 million by 2030. Breast, lung, thyroid, pancreatic, liver, prostate, bladder, kidney, pelvis, colon, and rectum cancers are the most prevalent. Each year, approximately 400,000 children develop cancer. Treatment between countries vary, but usually includes either surgery, radiotherapy, or chemotherapy. Modern treatments such as hormone-, immuno- and antibody-based therapies are becoming increasingly popular. Several recent reports have been published on toxins, antibiotics, bacteriocins, non-ribosomal peptides, polyketides, phenylpropanoids, phenylflavonoids, purine nucleosides, short chain fatty acids (SCFAs) and enzymes with anticancer properties. Most of these molecules target cancer cells in a selective manner, either directly or indirectly through specific pathways. This review discusses the role of bacteria, including lactic acid bacteria, and their metabolites in the treatment of cancer.

Keywords: bacteria; cancer treatment; lactic acid bacteria.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Mode of action of diphtheria toxin (DT). (A) The receptor (R domain) of DT, shown here as green speres, binds to the membrane-anchored precursor of heparin-binding epidermal-like growth factor (proHB-EGF). (B) DT is nicked and the DT-HB-EGF enters a clathrin-coated vesicle through endocytosis. Furin or furin-like proteases converts DT to mature form. (C) An early endosomal vesicle (EEV) is formed by replacing clathrin proteins with the GTPase Arf-1 and coat protein COPI (not shown). (D) EEV is acidified by the transport of protons (H+) across the membrane, instigated by vacuolar adenosine triphosphatase (vATPase). (E) The T-domain is translocated across the membrane, exposing the C-domain to the cytosol. (F) The disulphide bridge is reduced to liberate the catalytic C-domain. (G) The free C-domain catalyses the ADP-ribosylation of eukaryotic elongation factor 2 (eEF2) to ADPR-eEF2, which inhibits translation. This illustration was made using BioRender (https://biorender.com/, accessed on 12 May 2022).
Figure 2
Figure 2
Clostridium perfringens enterotoxin (CPE) mode of action. (A) Tyrosine residues in the C-terminal of CPE interact with the second extracellular loop (ECL-2) of a receptor claudin (CLDN) and form small complexes. (B) Approximately six small complexes oligomerize to form a larger CPE hexamer 1 (CH-1; prepore). (C) β-hairpin loops of CPE assemble to form a β-barrel that inserts into the cell membrane to create a cation-permeating pore. (D) Influx of Ca2+ ions disrupts the osmotic equilibrium and activates Ca2-dependent proteases to lyse the cell that forms calpain. (E) Release of cytochrome C from the mitochondrion. (F) Activation of caspase 3/7 and formation of a large new CH-2 complex (approximately 600 kDa, consisting of CLDNs, occludins and the CPE hexamer. (G and H) Apoptosis, leading to DNA fragmentation. This illustration was constructed using BioRender (https://biorender.com/, accessed on 12 May 2022).
Figure 3
Figure 3
Botulinum neurotoxin (BoNT) mode of action. (A) BoNT binds to ecto-acceptors (polysialogangliosides) on the presynaptic cell surface of cholinergic neurons and is internalized via SV-2 or Syt-mediated endocytosis. (B) The synaptic vesicle is acidified with vesicular proton pumps, which in turn (C) activates Ach transporter proteins. The activated transporter proteins import acetylcholine (Ach) and the light chain (LC) of BoNT is translocated to the cytosol (D) with the heavy chain (HC) domain. (E) Heat shock protein 90 (Hsp90) and thioredoxin reductase-thioredoxin (TrxR-Trx) cleaves the LC and (F) liberates it into the cytosol. (G) The C-domain is a Zn2+-dependent endopeptidase that cleaves proteins in the soluble N-ethylmaleimide-sensitive adaptor receptor (SNARE) protein complex. This complex is responsible for exocytosis and the fusing of acetylcholine-containing vesicles with the plasma membrane, allowing the release of acetylcholine. The cleaved SNARE component is non-functional, thereby blocking the release of acetylcholine from the presynaptic membrane to muscles. Blocking exocytosis of acetylcholine leads to failed skeletal muscle contracture. This representation was constructed using BioRender (https://biorender.com/, accessed on 12 May 2022).
Figure 4
Figure 4
Top of presentation: The four domains (Ia, II, Ib and III) of Pseudomonas exotoxin (PE), with the sizes of each domain indicated in amino acid numbers. Interaction of PE-IT (immunotoxin) with a cancer-specific antigen (CSA) or cancer-specific receptor (CSR) on the surface of cancer cells. Intracellular events leading to cell death is illustrated below the phospholipid membrane. Abbreviations: PE-L = Pseudomonas exotoxin A, fused to a cancer-specific ligand; Ab = antibody; EF2 = eukaryotic elongation factor-2 on ribosomes; Mcl1 = gene encoding anti-apoptotic protein; BAK = Bak protein involved in mitochondrion outer membrane (MOM) permeabilization; BCL-xL = B-cell lymphoma-extra large that inhibits the activation of Bak, thereby preventing a loss of MOM integrity. This illustration was constructed using BioRender (https://biorender.com/, accessed on 15 August 2022).
Figure 5
Figure 5
Azurin (128 amino acids), with an extended α-helix protein transduction domain, p28 (Leu50–Asp77), and four loop regions in its C-terminal (shown here in red, yellow, light blue and dark blue). The p28 peptide of 28 amino acids (amino acids 50 to 77) facilitates cell crossing and promotes apoptosis. Cell growth in tumours is repressed by 10 to 12 amino acids in the COOH terminal of p28. The α-helix, stretching over 18 amino acids (Leu50–Gly67), shown here as peptide p18, has a high affinity for cancer cells (less so for normal cells), excellent penetration abilities, and high binding to the tumour repressor protein p53. Peptide p18b also contains 18 amino acids (Val60–Asp77) but has a short α-helix and β-sheet and penetrates cancerous and normal cells. The p12 peptide of 12 amino acids (Gly66–Asp77) does not have an α-helical structure, binds poorly to p35, and penetrates cancer and normal cells. Adapted from Yaghoubi et al. [317].
Figure 6
Figure 6
Mode of action of Azurin. Once inside a cancer cell, azurin attaches to the DNA-binding domain of the tumour-suppressor protein p53 (middle of presentation) and prevents binding of the latter to E3 ubiquitin ligase COP1, resulting in an increase in cytoplasmic p53 levels. Cell growth is repressed, and cells are destroyed by apoptosis. Azurin also interferes with non-receptor tyrosine kinase (NRTK) signalling pathways. Bax protein (a central cell death regulator) and cytochrome C levels increase, and caspases 9 and 7 are activated. VEGFR-2 tyrosine kinase activity is reduced, preventing the formation of new blood vessels and the expression of P-cadherin. Prepared using BioRender (https://biorender.com/, accessed on 12 May 2022).

Similar articles

Cited by

References

    1. Siegel R.L., Miller K.D., Fuchs H.E., Jemal A. Cancer Statistics, 2022. Am. Cancer Soc. 2022;72:7–33. doi: 10.3322/caac.21708. - DOI - PubMed
    1. World Health Organization World Health Assembly, 70 Cancer Prevention and Control in the Context of an Integrated Approach. [(accessed on 21 June 2022)]. Available online: https://apps.who.int/iris/handle/10665/275676.
    1. National Institute for Communicable Diseases National Cancer Registry 2019, Full Report. [(accessed on 21 June 2022)]. Available online: https://www.nicd.ac.za/centres/national-cancer-registry/cancer-statistics.
    1. American Cancer Society, Cancer Facts and Figures. 2018. [(accessed on 20 June 2022)]. Available online: - DOI
    1. Soleimanpour S., Hasanian S.M., Avan A., Yaghoubi A., Khazaei M. Bacteriotherapy in gastrointestinal cancer. Life Sci. 2020;254:117754. doi: 10.1016/j.lfs.2020.117754. - DOI - PubMed

Grants and funding

This research received no external funding.

LinkOut - more resources