Treatment of cancer using bacteria and their products

Treatment of cancer using bacteria and their products
Fatemeh Tohidi,^1,*
1. Ale-Taha institute of Higher Education, Tehran, Iran.
Introduction: Cancer is one of the deadliest diseases in the world [1]. Bacteria and their spores, because they are selective for tumor tissues, also act as ideal vectors for delivering therapeutic proteins to tumors. Bacterial toxins have also emerged as promising cancer treatment strategies. The most promising strategy is prodrug enzyme therapy using genes. Although it has shown successful results in vivo, more research is needed on the mechanisms by which bacteria are targeted to develop a comprehensive therapeutic approach to cancer treatment [2].
Methods: An important factor that applies to the regression of cancer is the duality of the immune system [3]. Bacteria interact with the host as either pathogen or normal flora. The pathogenic interaction of bacteria enhances the immune system of the host in different ways [4]. certain bacteria have tumor finding nature defined as the ability to replicate inside tumor cells preferentially where the intracellular bacteria may evade host immunity. These approaches with bacteria so far have relied mostly on host immunity to indirectly impair cancer cells [5]. The production of pro-inflammatory cytokines such as IL-1𝛽 by lipopolysaccharides secreted by bacteria such as Salmonella typhimurium can damage cancer cells [4]. The fundamental advantage of bacteria-based cancer therapy is the capability to specifically target tumors via unique mechanisms. The use of Streptococcus pyogenes OK-432 in the successful treatment of sarcoma has shown promising results for the use of this bacterium in the treatment of lymphangiomas in children [6,7]. Bacterial toxins work by killing cells and altering the cellular processes that control the proliferation, apoptosis and differentiation associated with cancer. Another form of bacterial usage is spore, which are highly resistant bacterial forms. Other bacteria are used in the form of DNA vaccines, which stimulate the immune system against cancer cells by presenting cancer antigens. Bacteria growing under competition and drug influence are highly likely to evolve new phenotypes against cancer. the formed biofilm and the bacterial proteins are the products of the SOS response triggered by anti-proliferative drugs, such as hydroxyurea [8] that is an antiproliferative drug for tumor treatment, induces multicellularity of P. aeruginosa via impairing planktonic proliferation. Polysaccharides from Streptococcus agalactiae inhibit adhesion of cancer cells to endothelial cells—an essential step in cancer metastasis [1]. Salmonella, Clostridium and Bifidobacterium have been shown to control tumor growth and promote survival in animal models. However, Clostridium and Bifidobacterium are obligate anaerobes which limits their growth to the necrotic region of tumor and thus limits their effectiveness. In contrast, Salmonella is a facultative anaerobe which can grow in the viable as well as necrotic regions of tumors giving it greater potential as an anti-tumor agent. The S. typhimurium A1-R mutant, which is auxotrophic for Leu-Arg, has high anti-tumor virulence. In vitro, A1-R infects tumor cells and causes nuclear destruction. A1-R was initially used to treat metastatic human prostate and breast tumors that had been orthotopically implanted in nude mice. Substrains with tumor specific promoters and mutants which enhance selective tumor targeting have been identified [9,10]. Bacterial enzymes are one of the most important products of bacteria in the treatment of tumors. Bacteria such as Escherichia coli, Pseudomonas acidovorans, Beauveria bassiana, Acinetobacter can be used in the production of drugs as antitumors by producing enzymes such as L-asparaginase and L-glutaminase, L-tyrosinase, galactosidase [11]. L-asparaginase is among the main drugs used for the treatment of acute lymphoblastic leukemia and certain non-Hodgkin lymphoma. L-asparaginase has been isolated from various sources including bacteria, algae, fungi, plant and mammals. Currently, native asparaginase obtained from E. coli and Erwinia chrysanthemi are most frequently used for treatment of ALL [7,11].
Results: To enhance the positive consequences of bacterial cancer therapy, the usefulness of eukaryotic and prokaryotic expression systems for the delivery of therapeutic payloads, such as L-arabinose-inducible pBAD promoter, Acidosis-specific promoter, Quorum sensing and many others are used [12,13,14,15].
Conclusion: Anticancer therapy with the use of bacteria is often marginalized and neglected, But the positive effects of bacteria cannot be ignored. More studies are needed to investigate the clinical significance of cancer treatment and the beneficial properties of bacteria, but the findings so far show very promising results. Therefore, bacteria can be expected to be used with less harmful side effects in the treatment and control of cancer.
Keywords: Cancer, Treatment, Bacteria