The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy

Yun, Chul Won; Jeon, Juhee; Go, Gyeongyun; Lee, Jun Hee; Lee, Sang Hun

doi:10.3390/ijms22010179

Cited by 106 publications

(72 citation statements)

References 188 publications

(214 reference statements)

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“…p53, Bcl-2/Beclin 1, Atg proteins, p62 or caspases are the key factors connecting apoptosis and autophagy. As it was mentioned above caspases are engaged in both extrinsic and intrinsic apoptotic pathways, but also affect the autophagy process [ 47 ]. Oral et al demonstrated that overexpression of caspase-8 promotes the degradation of Atg3 protein and finally inhibits its pro-autophagic activity [ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Anti-HER2 monoclonal antibodies intensify the susceptibility of human gastric cancer cells to etoposide by promoting apoptosis, but not autophagy

et al. 2021

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Background Gastric cancer (GC) is a multifactorial disease with high mortality. Anti-HER2 therapy is a promising strategy in GC treatment and trastuzumab was approved by FDA (Food and Drug Administration) as the first and the second line of treatment of the disease. Purpose The aim of the study was to examine the effectiveness of a combination of etoposide with trastuzumab or pertuzumab in AGS gastric cancer cells and breast cancer cells such as MCF-7, MDA-MB-231 and HCC1954. Methods and findings The cytotoxic effects of the tested compounds against gastric and breast cancer cells were checked by MTT (3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide) assay. The anti-proliferative potential was analyzed by the incorporation of [3H]-thymidine into DNA. Fluorescent microscopy and flow cytometry was used to demonstrate the effect of the compounds on apoptosis. The mitochondrial membrane potential, and the activity of caspase-8 and caspase-9 were assessed. Autophagosomes and autolysosomes formation was checked by flow cytometry. The concentrations of Beclin-1, LC3A and LC3B were performed using ELISA. The expression of LC3A/B was also determined. The results from our study proved that the combination of etoposide with anti-HER2 antibodies was not cytotoxic against breast cancer cells, whereas the combination of etoposide with anti-HER2 antibodies decreased viability and DNA biosynthesis in gastric cancer cells. The interaction of etoposide with pertuzumab or trastuzumab induced programmed cell death via extrinsic and intrinsic apoptotic pathways in AGS gastric cancer cells, but did not affect autophagy, where a decrease of Beclin-1, LC3A and LC3B was observed in comparison with the untreated control. Conclusions The study demonstrated that etoposide (12.5 μM) with pertuzumab represent a promising strategy in gastric cancer treatment, but further in vivo examinations are also required.

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Section: Discussionmentioning

confidence: 99%

Anti-HER2 monoclonal antibodies intensify the susceptibility of human gastric cancer cells to etoposide by promoting apoptosis, but not autophagy

et al. 2021

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“…Autophagy has dichotomous roles in tumor promotion and suppression. In the early stages of cancer progression, autophagy acts as a tumor suppressor by removing damaged proteins and organelles, inhibiting inflammation, limiting genomic instability, inducing stress, and suppressing ROS production by the mitochondria (Lim and Murthy, 2020;Yun et al, 2020). In contrast, when tumors are already established, autophagy promotes cancer cell survival and growth by reprogramming metabolism, promoting angiogenesis, and promoting hypoxia and oxidative stress (Das et al, 2018;Thomas et al, 2018).…”

Section: Autophagy Triggeringmentioning

confidence: 99%

Icariside II: Anticancer Potential and Molecular Targets in Solid Cancers

et al. 2021

Front. Pharmacol.

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Icariside II, an active flavonoid, is extracted from the traditional Chinese medicinal herb Epimedii. It possesses multiple biological and pharmacological properties, including anti-inflammatory, anticancer, and anti-osteoporotic properties. In recent years, apoptosis has become the hot spot in anticancer therapies. Icariside II exerts positive effects on inducing apoptosis and inhibiting proliferation in various cancers. The antitumorigenic activity of Icariside II was also proven through cell cycle arrest, triggering autophagy, reducing cellular metabolism, and inhibiting cancer metastasis and tumor-associated angiogenesis. Additionally, Icariside II, as a natural product, contributed to a synergistic effect alongside chemotherapeutic drugs. Due to its poor aqueous solubility and permeability, more strategies were developed to improve its therapeutic effects. This review aimed to summarize the chemopreventive properties of Icariside II in solid tumors and reveal its underlying molecular mechanisms.

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“…Autophagy, as a ubiquitous survival pathway in cells, is closely linked with cancer, in which it plays a dual role as either a tumor suppressor or a tumor promoter ( Yun et al, 2021 ). In the early stage of tumorigenesis, autophagy maintains cellular homeostasis through protein and organelle quality control mechanisms ( Li et al, 2020 ).…”

Section: The Physiological Roles Of Autophagy In Different Adult Stem Cells and Related Diseasesmentioning

confidence: 99%

Role of Autophagy in the Maintenance of Stemness in Adult Stem Cells: A Disease-Relevant Mechanism of Action

Chen

Wang

Tan

et al. 2021

Front. Cell Dev. Biol.

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Autophagy is an intracellular scavenging mechanism induced to eliminate damaged, denatured, or senescent macromolecular substances and organelles in the body. The regulation of autophagy plays essential roles in the processes of cellular homeostasis and senescence. Dysregulated autophagy is a common feature of several human diseases, including cancers and neurodegenerative disorders. The initiation and development of these disorders have been shown to be associated with the maintenance of disease-specific stem cell compartments. In this review, we summarize recent advances in our understanding of the role of autophagy in the maintenance of stemness. Specifically, we focus on the intersection between autophagy and adult stem cells in the initiation and progression of specific diseases. Accordingly, this review highlights the role of autophagy in stemness maintenance from the perspective of disease-associated mechanisms, which may be fundamental to our understanding of the pathogeneses of human diseases and the development of effective therapies.

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The Dual Role of Autophagy in Cancer Development and a Therapeutic Strategy for Cancer by Targeting Autophagy

Cited by 106 publications

References 188 publications

Anti-HER2 monoclonal antibodies intensify the susceptibility of human gastric cancer cells to etoposide by promoting apoptosis, but not autophagy

Anti-HER2 monoclonal antibodies intensify the susceptibility of human gastric cancer cells to etoposide by promoting apoptosis, but not autophagy

Icariside II: Anticancer Potential and Molecular Targets in Solid Cancers

Role of Autophagy in the Maintenance of Stemness in Adult Stem Cells: A Disease-Relevant Mechanism of Action

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