Autophagy based cellular physiological strategies target oncogenic progression

Kumar, Prashant; Jagtap, Yuvraj Anandrao; Patwa, Som Mohanlal; Kinger, Sumit; Dubey, Ankur Rakesh; Prajapati, Vijay Kumar; Dhiman, Rohan; Poluri, Krishna Mohan; Mishra, Amit

doi:10.1002/jcp.30567

Cited by 6 publications

(3 citation statements)

References 241 publications

(327 reference statements)

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“…Autophagic degradation of various cell components has been reported to play vital roles in many pathological processes including stemness (Kumar et al, 2021). For example, nonsteroidal anti‐inflammatory drugs (NSAIDs) induced autophagy accompanied by the downregulation of CD44 and OCT4A in human chronic myeloid leukemia cells (Moon, Park, Lee, Kang, & Kim, 2019).…”

Section: Discussionmentioning

confidence: 99%

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Cheng

et al. 2022

Phytotherapy Research

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Capsaicin (CAP) is a well‐known anti‐cancer agent. Recently, we reported capsaicin‐induced apoptosis in anaplastic thyroid cancer (ATC) cells. It is well accepted that the generation of cancer stem cells (CSCs) is responsible for the dedifferentiation of ATC, the most lethal subtype of thyroid cancer with highly dedifferentiation status. Whether CAP inhibited the ATC growth through targeting CSCs needed further investigation. In the present study, CAP was found to induce autophagy in ATC cells through TRPV1 activation and subsequent calcium influx. Meanwhile, CAP dose‐dependently decreased the sphere formation capacity of ATC cells. The stemness‐inhibitory effect of CAP was further by extreme limiting dilution analysis (ELDA). CAP significantly decreased the protein level of OCT4A in both 8505C and FRO cells. Furthermore, CAP‐induced OCT4A degradation was reversed by autophagy inhibitors 3‐MA and chloroquine, BAPTA‐AM and capsazepine, but not proteasome inhibitor MG132. Collectively, our study firstly showed CAP suppressed the stemness of ATC cells partially via calcium‐dependent autophagic degradation of OCT4A. Our study lent credence to the feasible application of capsaicin in limiting ATC stemness.

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Section: Discussionmentioning

confidence: 99%

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Cheng

et al. 2022

Phytotherapy Research

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“…Autophagy removes damaged components of the cells and transfers harmful products to lysosomal degradation to prevent further cellular damage [ 8 ]. Autophagy also induces autophagic or programmed cell death to suppress cancer development [ 9 ]. Defects in autophagy can cause cellular damage to make genetically unstable cells, and initiate cancer development.…”

Section: An Overview Of Ulks In Autophagy and Cancersmentioning

confidence: 99%

Small Molecule Inhibitors for Unc-51-like Autophagy-Activating Kinase Targeting Autophagy in Cancer

Karmacharya

Jung

2023

IJMS

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Autophagy is a cellular process that removes damaged components of cells and recycles them as biochemical building blocks. Autophagy can also be induced to protect cells in response to intra- and extracellular stresses, including damage to cellular components, nutrient deprivation, hypoxia, and pathogenic invasion. Dysregulation of autophagy has been attributed to various diseases. In particular, autophagy protects cancer cells by supporting tumor cell survival and the development of drug resistance. Understanding the pathophysiological mechanisms of autophagy in cancer has stimulated the research on discovery and development of specific inhibitors targeting various stages of autophagy. In recent years, Unc-51-like autophagy-activating kinase (ULK) inhibitors have become an attractive strategy to treat cancer. This review summarizes recent discoveries and developments in small-molecule ULK inhibitors and their potential as anticancer agents. We focused on structural features, interactions with binding sites, and biological effects of these inhibitors. Overall, this review will provide guidance for using ULK inhibitors as chemical probes for autophagy in various cancers and developing improved ULK inhibitors that would enhance therapeutic benefits in the clinic.

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“…[ 2 ] To perform these functions, cancer cells depend on protein homeostasis and the necessary protein quality control (PQC) machinery; modulating them is an attractive therapeutic strategy. [ 3,4 ]…”

Section: Introductionmentioning

confidence: 99%

Valproate Mediated Proteasome Dysfunctions Induce Apoptosis

Kinger,

Jagtap,

Dubey

et al. 2024

Advanced Therapeutics

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Several studies suggest Valproate's (VPA) therapeutic use in treating seizures, epilepsy, and bipolar disorder. Valproate is a class I histone deacetylases (HDACs) inhibitor and an attractive chemotherapeutic agent for targeting cancer. Few reports suggest that Valproate can suppress cell growth and cell differentiation and is linked with anti‐tumor activity. However, Valproate‐associated anti‐tumoral function and intracellular signaling cascade‐mediated anti‐cellular proliferation activities still need to be better understood. This current study suggests that Valproate can elevate proteasomal dysfunctions, resulting in misfolded protein accumulation and abnormal mitochondrial functions that successively induce apoptosis. Present findings indicate that treatment of Valproate inhibits Proteasome activities and also aggravates accumulation of expanded polyglutamine proteins and other proteasomal substrates. Overall, the aggregation of aberrant proteins and mitochondrial dysfunctions are observed, such as cytochrome c release, and disturbed mitochondrial membrane potential. Treatment of Valproate induces apoptotic morphological changes and cell death. These observations suggest that Valproate can cause mitochondrial abnormalities associated with apoptosis. These findings can provide new possible insights and suggest molecular approaches for developing better and specific Proteasome inhibitors that can be better useful with other anti‐tumor drugs for treatment of cancer and other complex diseases.

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Autophagy based cellular physiological strategies target oncogenic progression

Cited by 6 publications

References 241 publications

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Capsaicin inhibits the stemness of anaplastic thyroid carcinoma cells by triggering autophagy‐lysosome mediated OCT4A degradation

Small Molecule Inhibitors for Unc-51-like Autophagy-Activating Kinase Targeting Autophagy in Cancer

Valproate Mediated Proteasome Dysfunctions Induce Apoptosis

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