Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer

Lee, Jennifer J.; Jain, Veena; Amaravadi, Ravi K.

doi:10.3390/ijms222212402

Cited by 11 publications

(11 citation statements)

References 79 publications

(120 reference statements)

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“…ERK is one of the classical signal transduction components of the MAPK family, and it can directly induce autophagy by upregulation of the expression of autophagy-related proteins such as LC3 and p62 (99). Rekha et al found that treatment with low doses of glucocorticoids increased oxidative stress levels and basal autophagy levels in osteocytes without increasing osteocyte apoptosis, whereas high doses of glucocorticoids enhanced osteocyte apoptosis.…”

Section: Ros/mapk/erkmentioning

confidence: 99%

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Autophagy in Bone Remodeling: A Regulator of Oxidative Stress

et al. 2022

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Bone homeostasis involves bone formation and bone resorption, which are processes that maintain skeletal health. Oxidative stress is an independent risk factor, causing the dysfunction of bone homeostasis including osteoblast-induced osteogenesis and osteoclast-induced osteoclastogenesis, thereby leading to bone-related diseases, especially osteoporosis. Autophagy is the main cellular stress response system for the limination of damaged organelles and proteins, and it plays a critical role in the differentiation, apoptosis, and survival of bone cells, including bone marrow stem cells (BMSCs), osteoblasts, osteoclasts, and osteocytes. High evels of reactive oxygen species (ROS) induced by oxidative stress induce autophagy to protect against cell damage or even apoptosis. Additionally, pathways such as ROS/FOXO3, ROS/AMPK, ROS/Akt/mTOR, and ROS/JNK/c-Jun are involved in the regulation of oxidative stress-induced autophagy in bone cells, including osteoblasts, osteocytes and osteoclasts. This review discusses how autophagy regulates bone formation and bone resorption following oxidative stress and summarizes the potential protective mechanisms exerted by autophagy, thereby providing new insights regarding bone remodeling and potential therapeutic targets for osteoporosis.

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Section: Ros/mapk/erkmentioning

confidence: 99%

Section: Regulation Of Autophagy In Oxidative Stressmentioning

confidence: 99%

Autophagy in Bone Remodeling: A Regulator of Oxidative Stress

et al. 2022

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“…As matrix metalloproteinases (MMPs) were correlated with tumor invasion via MAPK, MMPs were reduced upon the treatment with EGCG to revoke the activation of ERK and JNK, which prevented fibrosis, invasion, and migration of cancer cells ( Kim et al, 2004 ; Zhen et al, 2006 ; Ho et al, 2007 ; Zeng and Harris, 2014 ). Autophagy acts as an adaptive resistance mechanism upon the inhibition of MAPK ( Lee et al, 2021 ). MAPK signaling pathway did not solely regulate autophagy ( Raufi et al, 2021 ).…”

Section: Regulation Of Autophagy By Egcg and Green Tea Catechins In R...mentioning

confidence: 99%

Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer

Hung

Chen

et al. 2022

Front. Pharmacol.

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With a rich abundance of natural polyphenols, green tea has become one of the most popular and healthiest nonalcoholic beverages being consumed worldwide. Epigallocatechin-3-gallate (EGCG) is the predominant catechin found in green tea, which has been shown to promote numerous health benefits, including metabolic regulation, antioxidant, anti-inflammatory, and anticancer. Clinical studies have also shown the inhibitory effects of EGCG on cancers of the male and female reproductive system, including ovarian, cervical, endometrial, breast, testicular, and prostate cancers. Autophagy is a natural, self-degradation process that serves important functions in both tumor suppression and tumor cell survival. Naturally derived products have the potential to be an effective and safe alternative in balancing autophagy and maintaining homeostasis during tumor development. Although EGCG has been shown to play a critical role in the suppression of multiple cancers, its role as autophagy modulator in cancers of the male and female reproductive system remains to be fully discussed. Herein, we aim to provide an overview of the current knowledge of EGCG in targeting autophagy and its related signaling mechanism in reproductive cancers. Effects of EGCG on regulating autophagy toward reproductive cancers as a single therapy or cotreatment with other chemotherapies will be reviewed and compared. Additionally, the underlying mechanisms and crosstalk of EGCG between autophagy and other cellular processes, such as reactive oxidative stress, ER stress, angiogenesis, and apoptosis, will be summarized. The present review will help to shed light on the significance of green tea as a potential therapeutic treatment for reproductive cancers through regulating autophagy.

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“…Our results showed that the knockdown of RPIA in shRPIA#1 and shRPIA#2 A549 cells significantly diminished the cell proliferation ability, compared to the control cells (Figure 3c). [41][42][43]. Our previous studies indicated that the knockdown of RPIA can reduce cell proliferation and colony formation ability in liver cancer cells by modulating ERK signaling [15].…”

Section: Knockdown Of Rpia Decreases Colony Formation Ability and Cel...mentioning

confidence: 99%

Suppression of Ribose-5-Phosphate Isomerase a Induces ROS to Activate Autophagy, Apoptosis, and Cellular Senescence in Lung Cancer

Nieh

Chou

Wang

et al. 2022

IJMS

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Ribose-5-phosphate isomerase A (RPIA) regulates tumorigenesis in liver and colorectal cancer. However, the role of RPIA in lung cancer remains obscure. Here we report that the suppression of RPIA diminishes cellular proliferation and activates autophagy, apoptosis, and cellular senescence in lung cancer cells. First, we detected that RPIA protein was increased in the human lung cancer versus adjust normal tissue via tissue array. Next, the knockdown of RPIA in lung cancer cells displayed autophagic vacuoles, enhanced acridine orange staining, GFP-LC3 punctae, accumulated autophagosomes, and showed elevated levels of LC3-II and reduced levels of p62, together suggesting that the suppression of RPIA stimulates autophagy in lung cancer cells. In addition, decreased RPIA expression induced apoptosis by increasing levels of Bax, cleaved PARP and caspase-3 and apoptotic cells. Moreover, RPIA knockdown triggered cellular senescence and increased p53 and p21 levels in lung cancer cells. Importantly, RPIA knockdown elevated reactive oxygen species (ROS) levels. Treatment of ROS scavenger N-acetyl-L-cysteine (NAC) reverts the activation of autophagy, apoptosis and cellular senescence by RPIA knockdown in lung cancer cells. In conclusion, RPIA knockdown induces ROS levels to activate autophagy, apoptosis, and cellular senescence in lung cancer cells. Our study sheds new light on RPIA suppression in lung cancer therapy.

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Clinical Translation of Combined MAPK and Autophagy Inhibition in RAS Mutant Cancer

Cited by 11 publications

References 79 publications

Autophagy in Bone Remodeling: A Regulator of Oxidative Stress

Autophagy in Bone Remodeling: A Regulator of Oxidative Stress

Green Tea Epigallocatechin-3-Gallate Regulates Autophagy in Male and Female Reproductive Cancer

Suppression of Ribose-5-Phosphate Isomerase a Induces ROS to Activate Autophagy, Apoptosis, and Cellular Senescence in Lung Cancer

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