Infectious Diseases Are Analogous With Cancer. Hypothesis And Implications

Benharroch, Daniel; Osyntsov, Lidia

doi:10.7150/jca.3977

Cited by 27 publications

(23 citation statements)

References 35 publications

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“…As with cancer cells, bacteria can replicate indefinitely as long as a permissible growth condition is provided. Indeed, similarities between cancer cells and bacterial pathogens have been noted: high replication rates, damages to the host, spreading and dissemination within the host, and rapid development of resistance against therapeutic agents 41 . Even the immune response against bacterial pathogens has been used to treat certain types of tumor 42 – 44 .…”

Section: Discussionmentioning

confidence: 99%

The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus

Yeo

Arya

Kim

et al. 2018

Sci Rep

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In Staphylococcus aureus, an important Gram-positive human pathogen, the SaeRS two-component system is essential for the virulence and a good target for the development of anti-virulence drugs. In this study, we screened 12,200 small molecules for Sae inhibitors and identified two anti-cancer drugs, streptozotocin (STZ) and floxuridine (FU), as lead candidates for anti-virulence drug development against staphylococcal infections. As compared with STZ, FU was more efficient in repressing Sae-regulated promoters and protecting human neutrophils from S. aureus-mediated killing. FU inhibited S. aureus growth effectively whereas STZ did not. Intriguingly, RNA-seq analysis suggests that both compounds inhibit other virulence-regulatory systems such as Agr, ArlRS, and SarA more efficiently than they inhibit the Sae system. Both compounds induced prophages from S. aureus, indicating that they cause DNA damages. Surprisingly, a single administration of the drugs was sufficient to protect mice from staphylococcal intraperitoneal infection. Both compounds showed in vivo efficacy in a murine model of blood infection too. Finally, at the experimental dosage, neither compound showed any noticeable side effects on blood glucose level or blood cell counts. Based on these results, we concluded that STZ and FU are promising candidates for anti-virulence drug development against S. aureus infection.

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Section: Discussionmentioning

confidence: 99%

The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus

Yeo

Arya

Kim

et al. 2018

Sci Rep

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“…Both cancer and bacterial cells share similar properties, such as high rate of proliferation, rapid adjustment, and quick spreading within the host and aggressive disease progression. 5 To sustain such rapid proliferation, cancer and bacterial cells have to support DNA replication and production of RNA by increasing de novo nucleotide synthesis. Ribonucleotide reductase (RNR) is the key enzyme that catalyzes the reduction of ribonucleotides to their corresponding deoxyribonucleotides, thereby initiating DNA synthesis or repair, making it an important biomolecular target for drugs with anticancer and antibacterial properties.…”

Section: Introductionmentioning

confidence: 99%

New Water-Soluble Copper(II) Complexes with Morpholine–Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action

et al. 2018

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Six morpholine-(iso)thiosemicarbazone hybrids HL1–HL6 and their Cu(II) complexes with good-to-moderate solubility and stability in water were synthesized and characterized. Cu(II) complexes [Cu(L1–6)Cl] (1–6) formed weak dimeric associates in the solid state, which did not remain intact in solution as evidenced by ESI-MS. The lead proligands and Cu(II) complexes displayed higher antiproliferative activity in cancer cells than triapine. In addition, complexes 2–5 were found to specifically inhibit the growth of Gram-positive bacteria Staphylococcus aureus with MIC50 values at 2–5 μg/mL. Insights into the processes controlling intracellular accumulation and mechanism of action were investigated for 2 and 5, including the role of ribonucleotide reductase (RNR) inhibition, endoplasmic reticulum stress induction, and regulation of other cancer signaling pathways. Their ability to moderately inhibit R2 RNR protein in the presence of dithiothreitol is likely related to Fe chelating properties of the proligands liberated upon reduction.

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“…Cancer cells and bacterial cells causing infections share several properties, such as high replication rates, virulence, modalities of spreading within the host, rapid development of resistance mechanisms against chemotherapeutical agents (e.g., active efflux and mutations of the drug target), and a tendency to become more aggressive during disease progression [7]. In addition, it has recently been hypothesized that cancer cells utilize cell-cell communication systems analogous to those of bacterial cells (quorum sensing or QS), that allow them to successfully coordinate their attacks against the host [8,9].…”

Section: Introductionmentioning

confidence: 99%

Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

Soo

Kwan

Quezada

et al. 2017

CTMC

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Despite the fact that bacterial infections are one of the leading causes of death worldwide and that mortality rates are increasing at alarming rates, no new antibiotics have been produced by the pharmaceutical industry in more than a decade. The situation is so dire that the World Health Organization warned that we may enter a "post-antibiotic era" within this century; accordingly, bacteria resistant against all known antibiotics are becoming common and already producing untreatable infections. Although several novel approaches to combat bacterial infections have been proposed, they have yet to be implemented in clinical practice. Hence, we propose that a more plausible and faster approach is the utilization of drugs originally developed for other purposes besides antimicrobial activity. Among these are some anticancer molecules proven effective in vitro for eliminating recalcitrant, multidrug tolerant bacteria; some of which also protect animals from infections and recently are undergoing clinical trials. In this review, we highlight the similarities between cancer cells/tumors and bacterial infections, and present evidence that supports the utilization of some anticancer drugs, including 5-fluorouracil (5-FU), gallium (Ga) compounds, and mitomycin C, as antibacterials. Each of these drugs has some promising properties such as broad activity (all three compounds), dual antibiotic and antivirulence properties (5-FU), efficacy against multidrug resistant strains (Ga), and the ability to kill metabolically dormant persister cells which cause chronic infections (mitomycin C).

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Infectious Diseases Are Analogous With Cancer. Hypothesis And Implications

Cited by 27 publications

References 35 publications

The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus

The FDA-approved anti-cancer drugs, streptozotocin and floxuridine, reduce the virulence of Staphylococcus aureus

New Water-Soluble Copper(II) Complexes with Morpholine–Thiosemicarbazone Hybrids: Insights into the Anticancer and Antibacterial Mode of Action

Repurposing of Anticancer Drugs for the Treatment of Bacterial Infections

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