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•EMT, cancer stem cells and autophagy are the three main axes of cancer cell metastasis.•EMT and cancer stem cells are closely related to each other, play a key role in ...metastasis.•Crosslink between autophagy and EMT can open a novel scenario for molecular mechanism of metastasis.•Autophagy plays a dual role in cancer stem cells and metastasis.
Epithelial-mesenchymal transition (EMT) and Cancer stem-like cells (CSCs) are major factors contributing to the metastasis of cancer cells. Consequently, the signaling pathways involved in both processes are appropriate therapeutic targets in the treatment of metastasis. Autophagy is another process that has recently attracted the attention of many researchers; depending on the type of cancer and tissue and the stage of cancer, this process can play a dual role in the development of cancer cells. Studies on cancer cells have shown that different signaling pathways are involved in all three processes, namely, cancer stem cells, autophagy, and EMT. The purpose of this study was to investigate and elucidate the relationship between the effective signaling pathways in all three processes, which could play an effective role in determining appropriate therapeutic goals.
The heat shock protein (Hsps) superfamily, also known as molecular chaperones, are highly conserved and present in all living organisms and play vital roles in protein fate. The HspA1A (Hsp70‐1), ...called Hsp70 in this review, is expressed at low or undetectable levels in most unstressed normal cells, but numerous studies have shown that diverse types of tumor cells express Hsp70 at the plasma membrane that leads to resistance to programmed cell death and tumor progression. Hsp70 is released into the extracellular milieu in three forms including free soluble, complexed with cancer antigenic peptides, and exosome forms. Therefore, it seems to be a promising therapeutic target in human malignancies. However, a great number of studies have indicated that both intracellular and extracellular Hsp70 have a dual function. A line of evidence presented that intracellular Hsp70 has a cytoprotective function via suppression of apoptosis and lysosomal cell death (LCD) as well as that extracellular Hsp70 can promote tumorigenesis and angiogenesis. Other evidence showed intracellular Hsp70 can promote apoptosis and membrane‐associated/extracellular Hsp70 can elicit antitumor innate and adaptive immune responses. Given the contradictory functions, as a "double agent," could Hsp70 be a promising tool in the future of targeted cancer therapies? To answer this question, in this review, we will discuss the functions of Hsp70 in cancers besides inhibition and stimulation strategies for targeting Hsp70 along with their challenges.
The heat shock protein (Hsps) superfamily, also known as molecular chaperones, are highly conserved and present in all living organisms and play vital roles in protein fate. Given the contradictory functions, as a "double agent," could Hsp70 be a promising tool in the future of targeted cancer therapies? To answer this question, in this review, we will discuss the functions of Hsp70 in cancers besides the inhibition and stimulation strategies to target Hsp70 along with their challenges.
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•MicroRNAs in cancer cell metastasis by affecting various factors.•mir146a expression were associated with cancer cell metastasis as a dual role.•Therapeutic role of mircroRNAs ...through its effects on other gene expressions such as NF-kB, SIRT1, TNF- α and IL-1β..
MicroRNAs are ribonucleic acids that are single-stranded and endogenous non-coding acids that regulate gene expression in later stages of the translation process by binding to genomic regulatory sites. miR146a is mostly involved in the regulation of inflammatory systems and another process that role in the innate immune system. In the present review, we have focused on the recent acquisitions about the main role played by mir146a in the control of the immune system and tumorigenesis. The main purpose of this review article is to systematically investigate the mir146a and its role in regulating signaling pathways involved in cancer and the immune system as well as its involved therapeutic methods.
Systematic search of MEDLINE, Web of Science and Cochrane Library was conducted for all comparative studies from 2000 to 2019 with the limitations of the English language.
For a notable period of time, researchers have mainly focused on the therapeutic mechanisms of mir146a involved in the modulation of inflammatory and anti-inflammatory genes. We found that levels of mir146a expression were associated with cancer cell metastasis as a dual role (Inhibitory and stimulatory roles). The results of various studies also showed that this microRNA has a therapeutic role through its effects on other gene expressions such as NF-kB, SIRT1, TNF- α and IL-1β and leads to disease control.
Knowledge about alterations in mir146a regulation will give a better understanding of the molecular basis for various chronic inflammatory diseases and cancers.
Epigenetic mechanisms are gene regulatory processes that control gene expression and cellular identity. Epigenetic factors include the "writers", "readers", and "erasers" of epigenetic modifications ...such as DNA methylation. Accordingly, the nuclear protein Methyl-CpG-Binding Protein 2 (MeCP2) is a reader of DNA methylation with key roles in cellular identity and function. Research studies have linked altered DNA methylation, deregulation of MeCP2 levels, or
gene mutations to different types of human disease. Due to the high expression level of MeCP2 in the brain, many studies have focused on its role in neurological and neurodevelopmental disorders. However, it is becoming increasingly apparent that MeCP2 also participates in the tumorigenesis of different types of human cancer, with potential oncogenic properties. It is well documented that aberrant epigenetic regulation such as altered DNA methylation may lead to cancer and the process of tumorigenesis. However, direct involvement of MeCP2 with that of human cancer was not fully investigated until lately. In recent years, a multitude of research studies from independent groups have explored the molecular mechanisms involving MeCP2 in a vast array of human cancers that focus on the oncogenic characteristics of MeCP2. Here, we provide an overview of the proposed role of MeCP2 as an emerging oncogene in different types of human cancer.
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•Alantolactone increases the level of cellular ROS in cancer cells.•Alantolactone as a pharmacological agent, induced apoptosis in cancer cells.•Alantolactone suppresses cell cycle in ...cancer cells.•Alantolactone suppresses metastasis in cancer cells.
Cancer is considered as the main challenge of human communities, and it annually imposes a significant economic burden on society. Natural products have been used for treatment of many diseases including inflammation, infections, neurological disorders, atherosclerosis, asthma and cancer for many years. Sesquiterpene lactones (STLs) refers to a group of natural products with different biological activities. A type of STL that has recently attracted much attention is Alantolactone (ALT). In recent years, many studies have investigated the molecular mechanism of this compound affecting cancer cells and results suggest that this compound exerts its anticancer effects by providing free radicals and inhibiting some of the signaling pathways that are effective in progression of cancer cells. The present study is aimed to introduce the latest molecular mechanisms of ALT proposed by researchers in recent years.
Coronavirus disease 2019 or COVID-19, starting from Wuhan, China, in December 2019, is a pandemic situation affecting millions worldwide and has exerted a huge burden on healthcare infrastructure. ...Therefore, there is an urgent need to understand the molecular mechanisms underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and design novel effective therapeutic strategies for combating this pandemic. In this regard, special attention has been paid to the exosomes. These nanoparticles are extracellular vesicles with critical function in the pathogenesis of several diseases including viral sepsis. Therefore, they may be involved in the pathogenesis of COVID-19 infection and also may be a way for transferring viral components and infecting other neighbor cells. Exosomes also can be considered as a therapeutic strategy for treating COVID-19 patients or used as a carrier for delivering effective therapeutic agents. Therefore, in this review, we discussed the biogenesis and contents of exosomes, their function in viral infection, and their potential as a therapeutic candidate in treating COVID-19.
Introduction
P53, as a tumor suppressor gene, is believed to be one of the most mutated genes in cancer cells. The mutant forms of this protein often play a tumorigenic role in cancer cells. Recent ...evidence shows that p53 plays a critical role in the migration, metastasis, and invasion of cancer cells. The present article aims to investigate the molecular mechanism that induces metastasis in cancer cells generated by the mutant P53, and to highlight the compounds targeting mutant-p53 together with their clinical applications.
Methods
A detailed literature search was conducted to find information about the role of the mutant-p53 in the processes involved in metastasis in various databases.
Results
A growing body of evidence suggests that Mutant-p53 enhances tumor metastasis affecting the Epithelial-mesenchymal transition (EMT) process, cancer stem cells, angiogenesis, autophagy, anoikis, and any other mechanisms regarding metastasis.
Conclusions
Taken together, targeting mutant-p53 by altering the processes involved in metastasis could be a potential therapeutic strategy in the treatment of metastatic cancer.
Graphic abstract
Introduction
Cancer is the second major threat to human society and one of the main challenges facing healthcare systems. One of the main problems of cancer care is the metastases of cancer cells ...that cause 90% of deaths due to cancer. Multiple molecular mechanisms are involved in cancer cell metastasis. Therefore, a better understanding of these molecular mechanisms is necessary for designing restrictive strategies against cancer cell metastasis. Accumulating data suggests that MicroRNAs (miRNAs) are involved in metastasis and invasion of human tumors through regulating multiple genes expression levels that are involved in molecular mechanisms of metastasis. The goal of this review is to present the molecular pathways by which the miR 200 family manifests its effects on EMT, cancer stem cells, angiogenesis, anoikis, and the effects of tumor cell metastases.
Methods
A detailed literature search was conducted to find information about the role of the miR-200 family in the processes involved in metastasis in various databases.
Results
Numerous lines of evidence revealed an association between the mir-200 family and metastasis of human tumors by impressing processes such as cancer stem cells, EMT, angiogenesis, and anoikis.
Conclusions
Understanding the molecular mechanisms associated with metastasis in which the miR-200 family is involved can be effective in treating metastatic cancers.
Graphic abstract
Background and purpose: Ovarian cancer is one of the leading causes of cancer mortality in women. Despite the increase in cases of this cancer, the current therapeutic strategy is not effective. This ...study aimed to investigate the effect of cisplatin (Cis) with alantolactone (ALT) and ZnO nanoparticles (ZnONPs) in inducing apoptosis in SKOV3 ovarian cancer cells line.
Experimental approach: To evaluate the viability of SKOV3 cells and determine the IC50 of Cis, ALT, and ZnONPs, MTT assay was used. Real-time PCR and western blotting were used to evaluate the expression levels of genes (XIAP, cyclin D1, Bcl-2, Bax, and MDM2) and proteins (XIAP, cyclin D1, Bcl-2, Bax), respectively. Also, cellular ROS levels were assessed by fluorimetry.
Findings / Results: Our results showed that ALT and ZnONPs significantly increased the response to Cis in SKOV3 cells compared to the control and this response is remarkably increased in the triple combination (ALT-Cis-ZnONPs). The expression of XIAP, cyclin D1, and Bcl-2 genes and proteins in the groups treated with ALT, Cis, and ZnONPs as a single agent, double and triple combination were significantly reduced compared to the control, while Bax was generally shown an increase. Also, the level of intracellular ROS is higher in the treatment groups than in the control group and the highest increase was observed in the triple combination.
Conclusion and implications: Taken together, our data demonstrated the potential therapeutic approach of using ALT and ZnONPs that may enhance the apoptotic effects of Cis on the SKOV3 cells.
Mesenchymal stem cells (MSCs), as one of the leading cell-based therapy, have provided a strong link between clinical investigation and basic research. MSCs have been successfully employed in ...treating graft versus host disease (GvHD), autoimmune disease, and several other diseases, particularly with high immune activity. Recently, MSCs have attracted attention to treating untreatable viral infections such as severe coronavirus disease 2019 (COVID-19). Given that the Toll-like receptors (TLRs) are directly able to detect internal and external hazard signals, and their stimulation has an intense effect on the ability to grow, differentiate, migrate, and maintain MSCs, it seems stimulation of these receptors can have a direct impact on the interaction of MSCs and immune cells, altering the ability to modify immune system responses. Hence, this mini-review focused on TLRs’ critical roles in the polarization of MSCs for developing MSC-based therapy in viral infections. Consequently, according to the literature review, a polarization process, mediated by TLRs concerning anti-inflammatory and proinflammatory phenotype, may be considered for MSC-therapy against viral infections.
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