Withaferin A suppresses the up‐regulation of acetyl‐coA carboxylase 1 and skin tumor formation in a skin carcinogenesis mouse model

Li, Wenjuan; Zhang, Chunjing; Du, Hongwu; Huang, Vincent; Sun, Brandi; Harris, Jonathan; Richardson, Quitin; Shen, Xinggui; Jin, Rong; Li, Guohong; Kevil, Christopher G.; Gu, Xia; Shi, Runhua; Zhao, Yunfeng

doi:10.1002/mc.22423

Cited by 40 publications

(26 citation statements)

References 27 publications

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“…Enhanced lipogenesis provides an important source of material and energy for the growth of tumors [49]. This lipogenic conversion induces high expression and activity of key enzymes involved in the fatty acid synthesis in tumor cell, such as acetyl coenzyme A carboxylase (acetyl-CoA carboxylation, ACC) and fatty acid synthase (FAS) [50–53], which in turn promotes cancer cell proliferation and survival.…”

Section: Main Textmentioning

confidence: 99%

The role of YAP/TAZ activity in cancer metabolic reprogramming

et al. 2018

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In contrast to normal cells, which use the aerobic oxidation of glucose as their main energy production method, cancer cells prefer to use anaerobic glycolysis to maintain their growth and survival, even under normoxic conditions. Such tumor cell metabolic reprogramming is regulated by factors such as hypoxia and the tumor microenvironment. In addition, dysregulation of certain signaling pathways also contributes to cancer metabolic reprogramming. Among them, the Hippo signaling pathway is a highly conserved tumor suppressor pathway. The core oncosuppressive kinase cascade of Hippo pathway inhibits the nuclear transcriptional co-activators YAP and TAZ, which are the downstream effectors of Hippo pathway and oncogenic factors in many solid cancers. YAP/TAZ function as key nodes of multiple signaling pathways and play multiple regulatory roles in cancer cells. However, their roles in cancer metabolic reprograming are less clear. In the present review, we examine progress in research into the regulatory mechanisms of YAP/TAZ on glucose metabolism, fatty acid metabolism, mevalonate metabolism, and glutamine metabolism in cancer cells. Determining the roles of YAP/TAZ in tumor energy metabolism, particularly in relation to the tumor microenvironment, will provide new strategies and targets for the selective therapy of metabolism-related cancers.

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Section: Main Textmentioning

confidence: 99%

The role of YAP/TAZ activity in cancer metabolic reprogramming

et al. 2018

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“…To this end, overexpression of phosphorylated ACC1 has been detected among diverse malignancies, including prostate cancer and breast cancer [148]. Furthermore, ACC1 is responsible for malignant transformation of skin epithelial cells, whose depletion greatly suppresses tumor burden and progression [149]. Moreover, the TNF-α-AMPK-ACC1 axis is aberrantly activated among pancreatic cancer models, implying the ACC1 involvement in inflammation-induced tumorigenesis [150].…”

Section: Functions Of Ampk Signaling Components In Tumorigenesismentioning

confidence: 99%

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Cheng

Zhang

et al. 2016

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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AMP-activated protein kinase (AMPK) is a ubiquitously expressed metabolic sensor among various species. Specifically, cellular AMPK is phosphorylated and activated under certain stressful conditions, such as energy deprivation, in turn to activate diversified downstream substrates to modulate the adaptive changes and maintain metabolic homeostasis. Recently, emerging evidences have implicated the potential roles of AMPK signaling in tumor initiation and progression. Nevertheless, a comprehensive description on such topic is still in scarcity, especially in combination of its biochemical features with mouse modeling results to elucidate the physiological role of AMPK signaling in tumorigenesis. Hence, we performed this thorough review by summarizing the tumorigenic role of each component along the AMPK signaling, comprising of both its upstream and downstream effectors. Moreover, their functional interplay with the AMPK heterotrimer and exclusive efficacies in carcinogenesis were chiefly explained among genetically altered mice models. Importantly, the pharmaceutical investigations of AMPK relevant medications have also been highlighted. In summary, in this review, we not only elucidate the potential functions of AMPK signaling pathway in governing tumorigenesis, but also potentiate the future targeted strategy aiming for better treatment of aberrant metabolism-associated diseases, including cancer.

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“…Out of the dozens of withanolides isolated from the WS plant, Withaferin A (WA) has been shown to be the most potent and the most abundant withanolide in WS roots. WA is effective as a cancer preventive [3] [4] [5] and therapeutic [6] [7] [8] agent in in vivo experimental models suggesting a potential to be developed as an anti-cancer compound in humans. While several molecular targets of WA have been identified, the mechanism underlying its cytoprotective responses remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms

Palliyaguru

Chartoumpekis

Wakabayashi

et al. 2016

Free Radical Biology and Medicine

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Small molecules of plant origin offer presumptively safe opportunities to prevent carcinogenesis, mutagenesis and other forms of toxicity in humans. However, the mechanisms of action of such plant-based agents remain largely unknown. In recent years the stress responsive transcription factor Nrf2 has been validated as a target for disease chemoprevention. Withania somnifera (WS) is a herb used in Ayurveda (an ancient form of medicine in South Asia). In the recent past, withanolides isolated from WS, such as Withaferin A (WA) have been demonstrated to be preventive and therapeutic against multiple diseases in experimental models. The goals of this study are to evaluate withanolides such as WA as well as Withania somnifera root extract as inducers of Nrf2 signaling, to probe the underlying signaling mechanism of WA and to determine whether prevention of acetaminophen (APAP)-induced hepatic toxicity in mice by WA occurs in an Nrf2-dependent manner. We observed that WA profoundly protects wild-type mice but not Nrf2-disrupted mice against APAP hepatotoxicity. WA is a potent inducer of Nrf2-dependent cytoprotective enzyme expression both in vivo and in vitro. Unexpectedly, WA induces Nrf2 signaling at least in part, in a Keap1-independent, Pten/Pi3k/Akt-dependent manner in comparison to prototypical Nrf2 inducers, sulforaphane and CDDO-Im. The identification of WA as an Nrf2 inducer that can signal through a non-canonical, Keap1-independent pathway provides an opportunity to evaluate the role of other regulatory partners of Nrf2 in the dietary and pharmacological induction of Nrf2-mediated cytoprotection.

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Withaferin A suppresses the up‐regulation of acetyl‐coA carboxylase 1 and skin tumor formation in a skin carcinogenesis mouse model

Cited by 40 publications

References 27 publications

The role of YAP/TAZ activity in cancer metabolic reprogramming

The role of YAP/TAZ activity in cancer metabolic reprogramming

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

Withaferin A induces Nrf2-dependent protection against liver injury: Role of Keap1-independent mechanisms

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