Synthetic antiprotozoal thiazolide drug induced apoptosis in colorectal cancer cells: implications of IL-6/JAK2/STAT3 and p53/caspases-dependent signaling pathways based on molecular docking and in vitro study

Tantawy, Mohamed A.; El-Sherbeeny, Nagla A.; Helmi, Nawal; Alazragi, Reem; Salem, Neveen A.; Elaidy, Samah M.

doi:10.1007/s11010-020-03736-4

Cited by 29 publications

(15 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, the viral genome proteins ORF3a, ORF8b and E activate NLR signalling and JNK signalling, which then triggers caspase-1, NF-kB signalling, stimulate pro-inflammatory cytokines and induces cell apoptosis ( Freeman and Swartz, 2020 ; Shah, 2020 ). Nitazoxanide inhibited the production of pro-inflammatory cytokines TNF-α, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 in peripheral blood mononuclear cells ( Rossignol, 2016 ), exhibited downregulation of IL-6/JAK2/STAT3 pathway and significantly modulated the p53/caspases-dependent signalling pathways affecting apoptosis ( Tantawy et al, 2020 ). TIZ treatment reduced inflammation in macrophage cell lines by suppressing NF-κB, MAPK and PI3K/Akt/mTOR pathway ( Shou et al, 2019 ), whereas in case of LPS induced inflammatory microglia, TIZ treatment decreased the release of pro-inflammatory cytokines including TNF-α, IL-1β, IL-6, chemokines like CCL-2 and CCL-3, intrinsic nitric oxide synthase (iNOS) and cyclooxygenase2 (COX2) expression (X. W. Li et al, 2020 ; Trabattoni et al, 2016 ).…”

Section: Nitazoxanidementioning

confidence: 99%

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

Lokhande

Devarajan

2021

European Journal of Pharmacology

View full text Add to dashboard Cite

Section: Nitazoxanidementioning

confidence: 99%

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

Lokhande

Devarajan

2021

European Journal of Pharmacology

View full text Add to dashboard Cite

“…One example is AG490, a JAK2/STAT3 inhibitor, which could support the p53-p21 axis to induce Kaposi's sarcoma-associated herpesvirus (KSHV) lytic cycle activation in lymphoma cells or downregulate HSP90 as well as mtp53 expression in glioblastoma and pancreatic cancer cells [160,162]. Another example is nitazoxanide, an FDA-approved antiprotozoal agent which was proved to have dual inhibitory effects on IL-6/JAK2/STAT3 and p53-dependent signaling pathways in colorectal cancer (CRC) cells [163]. Nitazoxanide is currently used with a spectrum of antibacterial drugs in a recruiting clinical trial to treat neoplasms (NCT02366884).…”

Section: Pharmacological Strategies To Target Both P53 and Stat3 Activities In Cancer Cellsmentioning

confidence: 99%

STAT3 and p53: Dual Target for Cancer Therapy

et al. 2020

View full text Add to dashboard Cite

The tumor suppressor p53 is considered the “guardian of the genome” that can protect cells against cancer by inducing cell cycle arrest followed by cell death. However, STAT3 is constitutively activated in several human cancers and plays crucial roles in promoting cancer cell proliferation and survival. Hence, STAT3 and p53 have opposing roles in cellular pathway regulation, as activation of STAT3 upregulates the survival pathway, whereas p53 triggers the apoptotic pathway. Constitutive activation of STAT3 and gain or loss of p53 function due to mutations are the most frequent events in numerous cancer types. Several studies have reported the association of STAT3 and/or p53 mutations with drug resistance in cancer treatment. This review discusses the relationship between STAT3 and p53 status in cancer, the molecular mechanism underlying the negative regulation of p53 by STAT3, and vice versa. Moreover, it underlines prospective therapies targeting both STAT3 and p53 to enhance chemotherapeutic outcomes.

show abstract

“… 90 Scientists revealed similar phenotypes, including mitochondrial dysfunction and oxidative stress induction in ivermectin-treated chronic myeloid leukemia cells and in renal cell carcinoma correspondingly. 91 , 92 Interestingly, in Wang’s study, ivermectin exhibits renal cancer cell inhibitory effect while sparing the normal kidney cells, suggesting it potent in further clinical treatment. 92 In Zhang’s experiment, they demonstrated that ivermectin-induced mitochondrial damage leads to increased Bax/Bcl-2 ratio, which leads to cytoplasm c release and caspase-mediated cancer cell apoptosis.…”

Section: Mitochondria Disrupting Effect Of Antiparasitic Agentsmentioning

confidence: 99%

“… 91 , 92 Interestingly, in Wang’s study, ivermectin exhibits renal cancer cell inhibitory effect while sparing the normal kidney cells, suggesting it potent in further clinical treatment. 92 In Zhang’s experiment, they demonstrated that ivermectin-induced mitochondrial damage leads to increased Bax/Bcl-2 ratio, which leads to cytoplasm c release and caspase-mediated cancer cell apoptosis. 93 Altogether, these studies demonstrated that ivermectin targets mitochondrion and induces its dysfunction, leading to its antitumor effect.…”

Section: Mitochondria Disrupting Effect Of Antiparasitic Agentsmentioning

confidence: 99%

Progress in Redirecting Antiparasitic Drugs for Cancer Treatment

Huang¹,

He²,

Bing-hua³

et al. 2021

DDDT

View full text Add to dashboard Cite

Drug repurposing is a feasible strategy in developing novel medications. Regarding the cancer field, scientists are continuously making efforts to redirect conventional drugs into cancer treatment. This approach aims at exploring new applications in the existing agents. Antiparasitic medications, including artemisinin derivatives (ARTs), quinine-related compounds, niclosamide, ivermectin, albendazole derivatives, nitazoxanide and pyrimethamine, have been deeply investigated and widely applied in treating various parasitic diseases for a long time. Generally, their pharmacokinetic and pharmacodynamic properties are well understood, while the side effects are roughly acceptable. Scientists noticed that some of these agents have anticancer potentials and explored the underlying mechanisms to achieve drug repurposing. Recent studies show that these agents inhibit cancer progression via multiple interesting ways, inducing ferroptosis induction, autophagy regulation, mitochondrial disturbance, immunoregulation, and metabolic disruption. In this review, we summarize the recent advancement in uncovering antiparasitic drugs’ anticancer properties from the perspective of their pharmacological targets. Instead of paying attention to the previously discovered mechanisms, we focus more on newly emerging ones that are worth noticing. While most investigations are focusing on the mechanisms of their antiparasitic effect, more in vivo exploration in clinical trials in the future is necessary. Moreover, we also paid attention to what limits the clinical application of these agents. For some of these agents like ARTs and niclosamide, drug modification, novel delivery system invention, or drug combination are strongly recommended for future exploration.

show abstract

Synthetic antiprotozoal thiazolide drug induced apoptosis in colorectal cancer cells: implications of IL-6/JAK2/STAT3 and p53/caspases-dependent signaling pathways based on molecular docking and in vitro study

Cited by 29 publications

References 53 publications

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

A review on possible mechanistic insights of Nitazoxanide for repurposing in COVID-19

STAT3 and p53: Dual Target for Cancer Therapy

Progress in Redirecting Antiparasitic Drugs for Cancer Treatment

Contact Info

Product

Resources

About