Dual Roles of Autophagy and Their Potential Drugs for Improving Cancer Therapeutics

Shin, Dong Wook

doi:10.4062/biomolther.2020.155

Cited by 18 publications

(21 citation statements)

References 99 publications

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“…Autophagy is one of the mechanisms that has not yet been fully elucidated, but it is known to play a dual role in tumorigenesis and progression. Autophagic cell death can be effectively used as an alternative in the treatment of tumors that are resistant to apoptosis [ 159 ]. One of the best-studied regulators of autophagy is the PI3K/Akt/mTOR signaling pathway, a key cascade that connects mitogenic stimuli from the external environment with the intracellular signaling pathways and plays a key role in controlling cell growth and survival, and the cell cycle.…”

Section: Induction Of Cell Deathmentioning

confidence: 99%

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Michalková¹,

Mirossay²,

Gazdova³

et al. 2021

Cancers

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Although great progress has been made in the treatment of cancer, the search for new promising molecules with antitumor activity is still one of the greatest challenges in the fight against cancer due to the increasing number of new cases each year. Chalcones (1,3-diphenyl-2-propen-1-one), the precursors of flavonoid synthesis in higher plants, possess a wide spectrum of biological activities including antimicrobial, anti-inflammatory, antioxidant, and anticancer. A plethora of molecular mechanisms of action have been documented, including induction of apoptosis, autophagy, or other types of cell death, cell cycle changes, and modulation of several signaling pathways associated with cell survival or death. In addition, blockade of several steps of angiogenesis and proteasome inhibition has also been documented. This review summarizes the basic molecular mechanisms related to the antiproliferative effects of chalcones, focusing on research articles from the years January 2015–February 2021.

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Section: Induction Of Cell Deathmentioning

confidence: 99%

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Michalková¹,

Mirossay²,

Gazdova³

et al. 2021

Cancers

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“…P62 binds to ubiquitinated proteins and interacts with LC3, mediating ubiquitinated protein transport in the autophagic progress [35]. Autophagy plays an important role in the regulation of the in ammatory response [36,37]. The decrease in autophagy leads to a large number of depolarized mitochondria and leaked substances, including mitochondrial DNA and ROS [38,39].…”

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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“…Indeed, the amount of intracellular p62 decreases when autophagy is induced. On the contrary, a corresponding accumulation of the protein could be observed when autophagy is inhibited [29][30][31]. Atg7 is an essential protein for cell degradation.…”

Section: Adomet Inhibited 5-fu-induced Autophagy In Hct 116 P53+/+ and Lovo Colorectal Cancer Cellsmentioning

confidence: 99%

“…Atg7 is an essential protein for cell degradation. During the initiation of autophagy Atg7 functions as an E1-like ligase for ubiquitin-like proteins such as Atg8 and Atg12, which are needed for the autophagic vacuole formation [29][30][31]. Finally, LC3B is the main marker of autophagy, and its amount correlates with the extent of autophagosome formation.…”

Section: Adomet Inhibited 5-fu-induced Autophagy In Hct 116 P53+/+ and Lovo Colorectal Cancer Cellsmentioning

confidence: 99%

S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation

Mosca

Pagano

Borzacchiello

et al. 2021

IJMS

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Colorectal cancer (CRC) is the second deadliest cancer worldwide despite significant advances in both diagnosis and therapy. The high incidence of CRC and its poor prognosis, partially attributed to multi-drug resistance and antiapoptotic activity of cancer cells, arouse strong interest in the identification and development of new treatments. S-Adenosylmethionine (AdoMet), a natural compound and a nutritional supplement, is well known for its antiproliferative and proapoptotic effects as well as for its potential in overcoming drug resistance in many kinds of human tumors. Here, we report that AdoMet enhanced the antitumor activity of 5-Fluorouracil (5-FU) in HCT 116p53+/+ and in LoVo CRC cells through the inhibition of autophagy, induced by 5-FU as a cell defense mechanism to escape the drug cytotoxicity. Multiple drug resistance is mainly due to the overexpression of drug efflux pumps, such as P-glycoprotein (P-gp). We demonstrate here that AdoMet was able to revert the 5-FU-induced upregulation of P-gp expression and to decrease levels of acetylated NF-κB, the activated form of NF-κB, the major antiapoptotic factor involved in P-gp-related chemoresistance. Overall, our data show that AdoMet, was able to overcome 5-FU chemoresistance in CRC cells by targeting multiple pathways such as autophagy, P-gp expression, and NF-κB signaling activation and provided important implications for the development of new adjuvant therapies to improve CRC treatment and patient outcomes.

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Dual Roles of Autophagy and Their Potential Drugs for Improving Cancer Therapeutics

Cited by 18 publications

References 99 publications

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

Molecular Mechanisms of Antiproliferative Effects of Natural Chalcones

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

S-Adenosylmethionine Increases the Sensitivity of Human Colorectal Cancer Cells to 5-Fluorouracil by Inhibiting P-Glycoprotein Expression and NF-κB Activation

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