Advances in the Research of AMPK and its Subunit Genes

Liu, Wuyi; Jiang, Ruizhi

doi:10.3923/pjbs.2013.1459.1468

Cited by 20 publications

(15 citation statements)

References 55 publications

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“…The activation of the enzyme adenylyl cyclase catalyzes the conversion of ATP into cAMP (24). We investigated whether fisetin treatment by affecting cellular bioenergetics resulted in a decrease in ATP-cAMP ratio.…”

Section: Resultsmentioning

confidence: 99%

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Syed

Lall

Chamcheu

et al. 2014

Archives of Biochemistry and Biophysics

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The prognosis of malignant melanoma remains poor in spite of recent advances in therapeutic strategies for the deadly disease. Fisetin, a dietary flavonoid is currently being investigated for its growth inhibitory properties in various cancer models. We previously showed that fisetin inhibited melanoma growth in vitro and in vivo. Here, we evaluated the molecular basis of fisetin induced cytoxicity in metastatic human melanoma cells. Fisetin treatment induced endoplasmic reticulum (ER) stress in highly aggressive A375 and 451Lu human melanoma cells, as revealed by up- regulation of ER stress markers including IRE1α, XBP1s, ATF4 and GRP78. Time course analysis indicated that the ER stress was associated with activation of the extrinsic and intrinsic apoptotic pathways. Fisetin treated 2-D melanoma cultures displayed autophagic response concomitant with induction of apoptosis. Prolonged treatment (16 days) with fisetin in a 3-D reconstituted melanoma model resulted in inhibition of melanoma progression with significant apoptosis, as evidenced by increased staining of cleaved Caspase-3 in the treated constructs. However, no difference in the expression of autophagic marker LC-3 was noted between treated and control groups. Fisetin treatment to 2-D melanoma cultures resulted in phosphorylation and activation of the multifunctional AMPK-activated protein kinase (AMPK) involved in the regulation of diverse cellular processes, including autophagy and apoptosis. Silencing of AMPK failed to prevent cell death indicating that fisetin induced cytotoxicity is mediated through both AMPK-dependent and -independent mechanisms. Taken together, our studies confirm apoptosis as the primary mechanism through which fisetin inhibits melanoma cell growth and that activation of both extrinsic and intrinsic pathways contributes to fisetin induced cytotoxicity.

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Section: Resultsmentioning

confidence: 99%

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Syed

Lall

Chamcheu

et al. 2014

Archives of Biochemistry and Biophysics

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“…It was reported that chemotherapeutic agents induced necrotic or apoptotic cell death in cancer cells via the generation of ROS (41). But another report showed that fisetin treatment of A375.S2 melanoma cells resulted in a significant decrease in ROS level (28), while another reported that fisetin stimulated generation of ROS in U266 multiple myeloma cells and induced apoptosis through activation of AMP-activated protein kinase pathways in a ROS-dependent manner (42). Thus, based on these observations, fisetininduced modulation of ROS may be cell type-dependent.…”

Section: Discussionmentioning

confidence: 99%

Fisetin Induces Apoptosis of HSC3 Human Oral Cancer Cells Through Endoplasmic Reticulum Stress and Dysfunction of Mitochondria-mediated Signaling Pathways

Shih

Hung

Lee

et al. 2017

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Abstract. Background Western blotting was used to examine the levels of apoptotic-associated protein and results indicated that fisetin increased expression of pro-apoptotic proteins such as B-cell lymphoma 2 (BCL2) antagonist/killer (BAK) and BCL2-associated X (BAX) but reduced that of anti-apoptotic protein such as BCL2 and BCL-x, and increased the cleaved forms of caspase-3, -8 and -9, and cytochrome c, apoptosis-inducing factor (AIF) and endonuclease G (ENDO G) in HSC3 cells. Confocal microscopy showed that fisetin increased the release of cytochrome c, AIF and ENDO G from mitochondria into the cytoplasm. Conclusion: Based on these observations, we suggest that fisetin induces apoptotic cell death through endoplasmic reticulum stress-and mitochondria-dependent pathways.Oral cancer is a subtype of head and neck squamous cell carcinoma. Oral squamous cell carcinoma (OSCC) comprises of a large proportion of head and neck SCC (1). In men, oral cancer constitutes approximately 3% of all malignant 1103

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“…Similar to the α subunit, there are two isomers of β subunit, AMPKβ1 and AMPKβ2, each with specific tissue distributions. Specifically, liver is the main habitat of AMPKβ1, while AMPKβ2 is primarily expressed in skeletal muscles [25]. …”

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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Advances in the Research of AMPK and its Subunit Genes

Cited by 20 publications

References 55 publications

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Involvement of ER stress and activation of apoptotic pathways in fisetin induced cytotoxicity in human melanoma

Fisetin Induces Apoptosis of HSC3 Human Oral Cancer Cells Through Endoplasmic Reticulum Stress and Dysfunction of Mitochondria-mediated Signaling Pathways

Functional characterization of AMP-activated protein kinase signaling in tumorigenesis

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