Potential therapeutic targets shared between leishmaniasis and cancer

Rashidi, Sajad; Fernández-Rubio, Celia; Manzano-Román, Raúl; Mansouri, Reza; shafiei, reza; Ali‐Hassanzadeh, Mohammad; Barazesh, Afshin; Karimazar, Mohammadreza; Hatam, Gholamreza; Nguewa, Paul

doi:10.1017/s0031182021000160

Cited by 19 publications

(14 citation statements)

References 270 publications

(313 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several data have shown similar host responses against Leishmania and tumor progression [ 102 , 103 ]. Both parasite infection and tumor cells have to deal with the immune response to proliferate and survive, showing the importance of controlling immunological response favoring both models [ 104 , 105 ].…”

Section: Discussionmentioning

confidence: 99%

In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles

et al. 2021

View full text Add to dashboard Cite

Calcineurin (CaN) is present in all eukaryotic cells, including intracellular trypanosomatid parasites such as Trypanosoma cruzi (Tc) and Leishmania spp. (Lspp). In this study, we performed an in silico analysis of the CaN subunits, comparing them with the human (Hs) and looking their structure, post-translational mechanisms, subcellular distribution, interactors, and secretion potential. The differences in the structure of the domains suggest the existence of regulatory mechanisms and differential activity between these protozoa. Regulatory subunits are partially conserved, showing differences in their Ca2+-binding domains and myristoylation potential compared with human CaN. The subcellular distribution reveals that the catalytic subunits TcCaNA1, TcCaNA2, LsppCaNA1, LsppCaNA1_var, and LsppCaNA2 associate preferentially with the plasma membrane compared with the cytoplasmic location of HsCaNAα. For regulatory subunits, HsCaNB-1 and LsppCaNB associate preferentially with the nucleus and cytoplasm, and TcCaNB with chloroplast and cytoplasm. Calpain cleavage sites on CaNA suggest differential processing. CaNA and CaNB of these trypanosomatids have the potential to be secreted and could play a role in remote communication. Therefore, this background can be used to develop new drugs for protozoan pathogens that cause neglected disease.

show abstract

Section: Discussionmentioning

confidence: 99%

In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In past years, the link between leishmaniasis and cancer has been emphasized in both animal models and humans. The effects of VL and micronutrient deprivation are not restricted to infected individuals and their families; they also have an influence on a country's socioeconomic growth [27,28]. Patients with leishmaniasis had low levels of micronutrients in their blood.…”

Section: Leishmaniasis and Micronutrientsmentioning

confidence: 99%

The Possible Role of Selected Vitamins and Minerals in the Therapeutic Outcomes of Leishmaniasis

Kumar

Favas

Sharma

et al. 2022

Biol Trace Elem Res

View full text Add to dashboard Cite

Leishmaniasis is a protozoal disease declared as an endemic in areas suffering from severe malnutrition and poverty. The factors associated with poverty like low income, ecological factors, and malnutrition cause disruption in immunity and host defense increasing risk of infection. Altered resistance to infection and host susceptibility are associated with low micronutrient levels in undernourished patients. Malnutrition has been recognized as a poor predictive marker for leishmaniasis, in particular the deficiency of trace elements like zinc, iron, and vitamin A, B, C, D which has a prominent function in the regulation of innate and adaptive immunity, cell proliferation, human physiology, etc. Malnourishment can exacerbate host sensitivity and pathophysiologic intensity to infection in variety of ways, whereas infection can enhance underlying poor nutrition or enhance host vulnerability and sandfly's urge to attack specific hosts. The intensity of leishmaniasis can be influenced by body mass and micronutrient availability in the blood. Vitamin D, C, zinc, and iron are proved effective in inhibiting the growth of leishmaniasis in both amastigote or promastigote forms, either directly or by acting as precursor for a pathway which inhibits the parasite growth. This article elucidates a new perception to the crucial role of micronutrients and their probable role in the therapeutic outcomes of leishmaniasis. Since there is requirement of novel drugs to fight drug resistance and relapse of leishmaniasis, this article may pave way to understand the importance of micronutrients and their role in therapeutic outcomes of leishmaniasis.

show abstract

“…D609 has also demonstrated significant potential anti-inflammatory activities [ 77 ]. Immunization of uveal melanin protein causes experimental melanin–protein induced uveitis (EMIU), which is a form of chronic autoimmune uveitis.…”

Section: Pharmacological Properties Of D609mentioning

confidence: 99%

Tricyclodecan-9-yl-Xanthogenate (D609): Mechanism of Action and Pharmacological Applications

Bhat

Dar

Khan

et al. 2022

IJMS

View full text Add to dashboard Cite

Tricyclodecan-9-yl xanthogenate (D609) is a synthetic tricyclic compound possessing a xanthate group. This xanthogenate compound is known for its diverse pharmacological properties. Over the last three decades, many studies have reported the biological activities of D609, including antioxidant, antiapoptotic, anticholinergic, anti-tumor, anti-inflammatory, anti-viral, anti-proliferative, and neuroprotective activities. Its mechanism of action is extensively attributed to its ability to cause the competitive inhibition of phosphatidylcholine (PC)-specific phospholipase C (PC-PLC) and sphingomyelin synthase (SMS). The inhibition of PCPLC or SMS affects secondary messengers with a lipidic nature, i.e., 1,2-diacylglycerol (DAG) and ceramide. Various in vitro/in vivo studies suggest that PCPLC and SMS inhibition regulate the cell cycle, block cellular proliferation, and induce differentiation. D609 acts as a pro-inflammatory cytokine antagonist and diminishes Aβ-stimulated toxicity. PCPLC enzymatic activity essentially requires Zn2+, and D609 might act as a potential chelator of Zn2+, thereby blocking PCPLC enzymatic activity. D609 also demonstrates promising results in reducing atherosclerotic plaque formation, post-stroke cerebral infarction, and cancer progression. The present compilation provides a comprehensive mechanistic insight into D609, including its chemistry, mechanism of action, and regulation of various pharmacological activities.

show abstract

Potential therapeutic targets shared between leishmaniasis and cancer

Abstract: Abstract

Cited by 19 publications

References 270 publications

In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles

In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles

The Possible Role of Selected Vitamins and Minerals in the Therapeutic Outcomes of Leishmaniasis

Tricyclodecan-9-yl-Xanthogenate (D609): Mechanism of Action and Pharmacological Applications

Contact Info

Product

Resources

About