# Bacteriotherapy in Breast Cancer
## 3 Anticancer Substances Released by Bacteria
### Bacterial Toxins in Cancer Therapy
#### 3.3.1 Diphtheria Toxin  
Diphtheria toxin (DT), with a molecular mass of approximately 60 kDa and 538 amino acids, is an exotoxin produced by _Corynebacterium diphtheria_[68]. Diphtheria toxin is produced due to the infection of bacteria with bacteriophage B. The gene that encodes diphtheria toxin is the \"tox gene\" that is present in some corynebacteriophages, therefore, the tox phage strains are able to secrete diphtheria toxin. DT is the combination of two subunits, \"A\" and \"B\". Subunit \"B\" is responsible for binding to the receptor and translocation. Subunit \"A\" inhibits protein synthesis by ADP-ribosylation of cytoplasmic elongation factor 2 (EF-2), and therefore leads to cell death [75]. The anticancer activity has been shown  
\begin{table}
\begin{tabular}{c c c c c} \hline \hline
**Toxins** & **Source** & **Breast Cancer Cell Line** & **Other Human Cancer Cells/Cell Lines** & **Ref** \\ \hline \multirow{6}{*}{Diphtheria toxin} & \multirow{6}{*}{_Corynebacterium diphtheria_} & \multirow{6}{*}{MCF 7} & \multicolumn{2}{c}{Adenocortical carcinoma (H295R), glioblastomas (U118 MG, U373 MG, U87 MG), cutaneous T cell lymphomas (CTCL), cervical adenocarcinoma (HeLa), colon cancer (SW480, SW620, HCT116, CaCo-2, and HT-29) prostate cancer (PC-3, INCaP) [69; 70] neuroblastoma (SH-SF57) pancreatic cancer (PaCa-2), melanomas (FEMX, Melmet-1, Melmet-4, MeltRM, MM200), head neck squamous carcinomas, [PERSON]’s lymphoma (Daudi, CA46), leukemias (HEIE, MEC1) [69; 71] murine-derived fibrosarcoma cell line (MCA-205), human melanoma (A375), human lung adenocarcinoma (Call-3), murine lung carcinoma (LLC1), human ovarian adenocarcinoma (GK-OV-3), human cervical adenocarcinoma (HeLa) [74] \\ \cline{1-1} \cline{2-5}  & \multirow{6}{*}{_Cityulation botulinum_} & \multirow{6}{*}{T47D, MDA-MB-231, MDA-MB-453} & \multirow{6}{*}{MCF 7} & \multirow{6}{*}{MCF 7} \\ \cline{1-1} \cline  
in another study on experimental models and human's diphtheia toxin (DT). The nontoxic mutant of diphtheia toxin is the cross-reacting material 197 (CRM197) that can bind to heparin-binding epidermal growth factor-like growth factor. CRM197 can inhibit the growth, reduce the angiogenesis, and induce the apoptosis in human adrenocortical carcinoma. Moreover, it acts as an immunological adjuvant and inhibits the heparin-binding epidermal growth factor [76]. DT is used in conjunction with other substances to reduce the related side effects. According to a study, the cytotoxicity activity of CRM197 is enhanced in combination with other substances. CRM197 in combination with doxorubicin, as the cytotoxicity of CRM197, was improved in a T-cell acute lymphoblastic leukemia cell lines. Additionally, the combination with cisplatin inhibits the growth and induces the apoptosis in glioma cells. DTAT is another substance with which the DT-based immunotoxin targets the tumor vascular endothelium. DTAT has anticancer activity in vitro against uPAR-expressing glioblastoma cells (U118 MG, U373 MG, and U87 MG). Furthermore, it can be the cause of regression of small U118 MG cell-induced tumors in mice. Diphtheia toxin has shown anticancer activity against breast carcinoma (MCF 7) [66; 67; 77].