Targeting Autophagy in Breast Cancer

Cocco, Stefania; Leone, Alessandra; Piezzo, Michela; Caputo, Roberta; Lauro, Vincenzo Di; Rella, Francesca Di; Fusco, Giuseppina; Capozzi, Monica; Gioia, Germira Di; Budillon, Alfredo; Laurentiis, Michelino De

doi:10.3390/ijms21217836

Cited by 64 publications

(54 citation statements)

References 185 publications

(213 reference statements)

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“…The PI3K/Akt/mTOR pathway plays an important role in the regulation of the cells’ cycle; it impacts the development and differentiation of cells [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. The PI3K/Akt/mTOR signaling pathway plays an important role in the processes of tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study

Kołodziej

Nicoś

Krawczyk

et al. 2021

IJMS

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There is an urgent need to seek new molecular biomarkers helpful in diagnosing and treating breast cancer. In this elaboration, we performed a molecular analysis of mutations and expression of genes within the PI3K/Akt/mTOR pathway in patients with ductal breast cancer of various malignancy levels. We recognized significant correlations between the expression levels of the studied genes. We also performed a bioinformatics analysis of the data available on the international database TCGA and compared them with our own research. Studies on mutations and expression of genes were conducted using High-Resolution Melt PCR (HRM-PCR), Allele-Specific-quantitative PCR (ASP-qPCR), Real-Time PCR molecular methods in a group of women with ductal breast cancer. Bioinformatics analysis was carried out using web source Ualcan and bc-GenExMiner. In the studied group of women, it was observed that the prevalence of mutations in the studied PIK3CA and AKT1 genes was 29.63%. It was stated that the average expression level of the PIK3CA, PIK3R1, PTEN genes in the group of breast cancer patients is lower in comparison to the control group, while the average expression level of the AKT1 and mTOR genes in the studied group was higher in comparison to the control group. It was also indicated that in the group of patients with mutations in the area of the PIK3CA and AKT1 genes, the PIK3CA gene expression level is statistically significantly lower than in the group without mutations. According to our knowledge, we demonstrate, for the first time, that there is a very strong positive correlation between the levels of AKT1 and mTOR gene expression in the case of patients with mutations and without mutations.

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Section: Introductionmentioning

confidence: 99%

The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study

Kołodziej

Nicoś

Krawczyk

et al. 2021

IJMS

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“…Microtubule-associated protein light chain 3 LC3 and p62 are critical proteins in autophagy. In particular, cytoplasmic soluble LC3 (LC3I) is hydrolyzed during the autophagic process to form the membrane-bound LC3 (LC3II), with the increase in LC3II/I thus being indicative of enhancement of autophagy [33,34]. P62 binds to ubiquitinated proteins and interacts with LC3, mediating ubiquitinated protein transport in the autophagic progress [35].…”

Section: Discussionmentioning

confidence: 99%

Kaempferol alleviates corneal transplantation rejection by inhibiting NLRP3 inflammasome activation and macrophage M1 polarization via promoting autophagy

Tian

Lin

et al. 2021

Experimental Eye Research

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Corneal transplantation rejection remains a major threat to the success rate in high-risk patients. Given the many side effects presented by traditional immunosuppressants, there is an urgency to clarify the mechanism of corneal transplantation rejection and to identify new therapeutic targets. Kaempferol is a natural avonoid that has been proven in various studies to possess anti-in ammatory, antioxidant, anticancer, and neuroprotective properties. However, the relationship between kaempferol and corneal transplantation remains largely unexplored. To address this, both in vivo and in vitro, we established a model of corneal allograft transplantation in Wistar rats and an LPS-induced in ammatory model in THP-1 derived human macrophages. In the transplantation experiments, we observed an enhancement in the NLRP3 / IL-1 β axis and in M1 macrophage polarization post-operation. In groups to which kaempferol intraperitoneal injections were administered, this response was effectively reduced. However, the effect of kaempferol was reversed after the application of autophagy inhibitors. Similarly, in the in ammatory model, we found that different concentrations of kaempferol can reduce the LPS-induced M1 polarization and NLRP3 in ammasome activation. Moreover, we con rmed that kaempferol induced autophagy and that autophagy inhibitors reversed the effect in macrophages. In conclusion, we found that kaempferol can inhibit the activation of the NLRP3 in ammasomes by inducing autophagy, thus inhibiting macrophage polarization, and ultimately alleviating corneal transplantation rejection. Thus, our study suggests that kaempferol could be used as a potential therapeutic agent in the treatment of allograft rejection.

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“…It is highly indicative that expression of the LC3B autophagosome marker was found to be higher in node-positive vs. node-negative primary breast tumors and associated with an increased nuclear grade and shortened survival, and that higher expression of the autophagy-promoting factor Beclin-1 in triple-negative breast cancers (TNBCs) was correlated with an increase of lymph node and distant metastases in patients [7,8]. On the other hand, a number of autophagy-restraining isolated compounds and secretomes, including the histone deacetylase inhibitors and conditioned media which were examined in [9][10][11][12], have been shown to restore the inhibition of survival, the impairment of cell cycle progression, and the induction of cell death programs in breast cancer cell cultures [13][14][15]. Thus, with the warning to take the specific breast cancer subtype and treatment used into consideration, nevertheless, the cumulative preclinical data obtained prompt the development of novel autophagy-targeting agents as a valuable strategy to improve the efficacy of anticancer interventions.…”

Section: A Brief Insight Into Autophagy and Breast Cancer Cellsmentioning

confidence: 99%

“…This organism proved to be a good source of araguspongine/xestospongine alkaloids, dimeric 2,9-disubstituted 1-oxaquinolizidines that have been shown to possess a variety of pharmacological activities [51,52]. In 2015, Akl et al [53] reported that araguspongine C ((1R,8R,10S,15R,22R,29S)-9,30-dioxa-11,25-diazapentacyclo[20.6.2.2 8,11 .0 10,15 .0 25,29 ]dotriacontane-1,15-diol; Figure 8) exerted an antiproliferative effect on a panel of breast cancer cell lines in culture. More detailed analyses aimed at identifying the cause of the accumulation of vacuoles in BT-474 breast tumor cells revealed the dose-dependent ability of araguspongine C to stimulate autophagy, as revealed by the increase in the accumulation of fluorescent autophagosomes and the upregulation of the total protein levels of LC3, Beclin-1, and ATG-5, -7, and -16L1.…”

Section: Autophagy Modulators From Poriferamentioning

confidence: 99%

Marine Animal-Derived Compounds and Autophagy Modulation in Breast Cancer Cells

Luparello

2021

Foundations

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It is known that in breast cancer biology, autophagy mainly plays a cytoprotective and anti-apoptotic role in vitro, being conceivably responsible for cell resistance to drug exposure and a higher metastatic attitude in vivo. Thus, the development of novel autophagy-targeting agents represents a valuable strategy to improve the efficacy of anticancer interventions. It is widely acknowledged that the enormous biodiversity of marine organisms represents a highly promising reserve for the isolation of bioactive primary and secondary metabolites targeting one or several specific molecular pathways and displaying active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of marine animal-derived extracts or isolated compounds which exert a modulatory effect on the autophagic process in breast cancer cells and list them with respect to the taxonomical hierarchy of the producing species. Where available, the molecular and biochemical aspects associated with the molecules or extracts under discussion will be also summarized.

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Targeting Autophagy in Breast Cancer

Cited by 64 publications

References 185 publications

The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study

The Correlation of Mutations and Expressions of Genes within the PI3K/Akt/mTOR Pathway in Breast Cancer—A Preliminary Study

Kaempferol alleviates corneal transplantation rejection by inhibiting NLRP3 inflammasome activation and macrophage M1 polarization via promoting autophagy

Marine Animal-Derived Compounds and Autophagy Modulation in Breast Cancer Cells

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