Autophagy in Cancer Cell Death

Linder, Benedikt; Kögel, Donat

doi:10.3390/biology8040082

Cited by 77 publications

(60 citation statements)

References 92 publications

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“…[ 228 , 229 ]. Autophagic cell death is important in reducing the viability of cancer cells [ 230 , 231 ]. Chrysin enhances levels of light chain-3 II (LC-3II) to induce autophagy.…”

Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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Pharmacological profile of phytochemicals has attracted much attention to their use in disease therapy. Since cancer is a major problem for public health with high mortality and morbidity worldwide, experiments have focused on revealing the anti-tumor activity of natural products. Flavonoids comprise a large family of natural products with different categories. Chrysin is a hydroxylated flavonoid belonging to the flavone category. Chrysin has demonstrated great potential in treating different disorders, due to possessing biological and therapeutic activities, such as antioxidant, anti-inflammatory, hepatoprotective, neuroprotective, etc. Over recent years, the anti-tumor activity of chrysin has been investigated, and in the present review, we provide a mechanistic discussion of the inhibitory effect of chrysin on proliferation and invasion of different cancer cells. Molecular pathways, such as Notch1, microRNAs, signal transducer and activator of transcription 3 (STAT3), nuclear factor-kappaB (NF-κB), PI3K/Akt, MAPK, etc., as targets of chrysin are discussed. The efficiency of chrysin in promoting anti-tumor activity of chemotherapeutic agents and suppressing drug resistance is described. Moreover, poor bioavailability, as one of the drawbacks of chrysin, is improved using various nanocarriers, such as micelles, polymeric nanoparticles, etc. This updated review will provide a direction for further studies in evaluating the anti-tumor activity of chrysin.

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“…[ 228 , 229 ]. Autophagic cell death is important in reducing the viability of cancer cells [ 230 , 231 ]. Chrysin enhances levels of light chain-3 II (LC-3II) to induce autophagy.…”

Section: Chrysin and Cancermentioning

confidence: 99%

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

et al. 2020

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“…Autophagy can have dual roles in the context of cancer as mentioned above it may have prosurvival effects and on the other hand it is also recognized as a cell death pathway. Long-lasting activation of the autophagosomal/lysosomal pathway can lead to autophagic cell death [ 25 ]. In vitro experiments show that high doses of DNA damaging cytostatics induce autophagic cell death [ 26 ].…”

Section: Lysosomes V-atpases and Cancermentioning

confidence: 99%

Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition

Hraběta

Belhajová

Šubrtová

et al. 2020

IJMS

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Resistance to chemotherapeutics and targeted drugs is one of the main problems in successful cancer therapy. Various mechanisms have been identified to contribute to drug resistance. One of those mechanisms is lysosome-mediated drug resistance. Lysosomes have been shown to trap certain hydrophobic weak base chemotherapeutics, as well as some tyrosine kinase inhibitors, thereby being sequestered away from their intracellular target site. Lysosomal sequestration is in most cases followed by the release of their content from the cell by exocytosis. Lysosomal accumulation of anticancer drugs is caused mainly by ion-trapping, but active transport of certain drugs into lysosomes was also described. Lysosomal low pH, which is necessary for ion-trapping is achieved by the activity of the V-ATPase. This sequestration can be successfully inhibited by lysosomotropic agents and V-ATPase inhibitors in experimental conditions. Clinical trials have been performed only with lysosomotropic drug chloroquine and their results were less successful. The aim of this review is to give an overview of lysosomal sequestration and expression of acidifying enzymes as yet not well known mechanism of cancer cell chemoresistance and about possibilities how to overcome this form of resistance.

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“…Some authors have actually observed that the depletion of autophagy decreased the viability of chronic myeloid leukemia CD34+ progenitor cells, whereas its inhibition in hematopoietic stem cells (HSC) has favored the development of hematopoietic diseases (Auberger and Puissant, 2017;Levine and Kroemer, 2019). On the other hand, after treatment with synthetic or natural compounds, there are some evidences that when the autophagosomal/lysosomal pathway is over activated for a prolonged time the autophagic cell death (ACD, type II cell death) can occur (Liao et al, 2019;Linder and Kögel, 2019). Arsenic trioxide (ATO) has been proved to induce ACD in several cancer cells.…”

Section: Autophagy In Cancermentioning

confidence: 99%

The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance

Condello¹,

Mancini

Meschini³

2020

Front. Pharmacol.

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Autophagy is a mechanism involved in many human diseases and in cancers can have a cytotoxic/cytostatic or protective action, being in the latter case involved in multidrug resistance. Understanding which of these roles autophagy has in cancer is thus fundamental for therapeutical decisions because it permits to optimize the therapeutical approach by activating or inhibiting autophagy according to the progression of the disease. However, a serious drawback of cancer treatment is often the scarce availability of drugs and autophagy modulators at the sites of interest. In the recent years, several nanocarriers have been developed and investigated to improve the solubility, bioavailability, controlled release of therapeutics and increase their cytotoxic effect on cancer cell. Here we have reviewed only liposomes as carriers of chemotherapeutics and autophagy inhibitors because they have low toxicity and immunogenicity and they are biodegradable and versatile. In this review after the analysis of the dual role of autophagy, of the main autophagic pathways, and of the role of autophagy in multidrug resistance, we will focus on the most effective liposomal formulations, thus highlighting the great potential of these targeting systems to defeat cancer diseases.

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Autophagy in Cancer Cell Death

Cited by 77 publications

References 92 publications

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Broad-Spectrum Preclinical Antitumor Activity of Chrysin: Current Trends and Future Perspectives

Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition

The Exploitation of Liposomes in the Inhibition of Autophagy to Defeat Drug Resistance

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