Introduction: Introduction
Human cancers are often associated with upregulation of proto-oncogenes and (or) downregulation of tumor suppressor genes. Investigation of the signal transduction pathways which participate in cancer development can lead to development of new drugs with both greater tumor cell specificity and improved efficacy. Recently it has been shown that some antibacterial agents have potential anti-cancer activities. Among many studies which support the anti-cancer properties of antibiotics, we provide several examples to highlight this very important issue.
Methods: We investigated Scopus and PubMed databases from 2010 through 2021 with keyword combination of “anti-cancer/anti-tumor” and “antibiotics”. We reached to 2,331 articles and based on the aim of the search, outcomes of interest included studies investigating signaling pathways affected by clinical antibiotics. Our data doesn’t include the combination of antibiotic therapy.
Results: Azithromycin, A Food and Drug Administration‑approved antibiotic which has different anti-tumor effects including inhibition of tumor angiogenesis in lung cancer via blocking of vascular endothelial growth factor receptor 2 (VEGFR2)‑mediated downstream signaling pathways.
Fluoroquinolones are broad spectrum antibiotics which includes Ciprofloxacin as an example. Some of the Ciprofloxacin anti-tumor activities are: decreasing cell viability, inducing morphological changes plus S-phase cell cycle arrest, and induction of cell apoptosis through mitochondria dependent pathways in COLO829 melanoma cells. In addition, increasing in Bax levels and Bax/Bcl-2 ratio, and also a decrease in Bcl-2 concentrations in the human glioblastoma A-172 cell line are among other reported anti-cancer activities of Ciprofloxacin.
Rapamycin-induced morphological changes of MCF-7 cells can lead to apoptosis. This macrolide fungicide has also been reported to prevent cell cycle progression of MCF-7 cells at the G0/G1 phase.
Tigecycline which has a broad antibacterial spectrum against gram-positive and gram-negative pathogens, suppresses the activities of the mitochondrial-encoded proteins, Cox-1 and Cox-2 and therefore, results in downregulation of the mitochondrial electron transport respiratory chain and a reduction in oxygen consumption rate in Chronic myeloid leukemia (CML) cells. Tigecycline inhibits the proliferation of CML primary cells and cell lines including the drug-sensitive and drug-resistant cells and also induces autophagy by downregulating the PI3K-AKT-mTOR signaling pathway resulting in cell death by activation of cytochrome-c/caspase-9/caspase-3 pathway. Also, Tigecycline induces autophagy in gastric cancer cells probably through suppression of mTOR/p70S6K phosphorylation.
Monensin, an ionophoric antibiotic isolated from Streptomyces cinnamonensis, promotes apoptosis of melanoma cells via an increase in both expression of melanin granules and tyrosinase activity. This antibiotic also decreases clone and sphere formation of melanoma stem cells. The down-regulation of tyrosinase-related protein 2 (TRP-2) and Sox10 protein activity together with up-regulation of TRP1 have been linked to the increase in differentiation and the decrease in pluripotency of melanoma cells. This antibiotic shows anti-angiogenic activity by inhibiting capillary network formation, growth, migration and survival of endothelial cells. Furthermore, Monensin effectively targets tumor-associated endothelial cells and therefore, results in inhibition of glioblastoma angiogenesis and tumor growth.
Conclusion: The above examples plus many other laboratory and clinical results support that antibacterial drugs may have potential anti-cancer properties. These findings provide new directions toward searching novel anti-cancer drugs with more specificity and less side effects.