Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling

Chen, San‐Yuan; Lin, Chun‐Hsiang; Lin, Jiun‐Tsai; Cheng, Yingying; Chen, Han-Min; Kao, Shao‐Hsuan

doi:10.3892/ol.2017.6890

Cited by 10 publications

(20 citation statements)

References 32 publications

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“…In contrast, supplementing the diet of adult APRT mutants with adenine, restored the AMP : ATP ratio to that of control flies and abolished the effect on longevity. As the authors note, these results are counterintuitive to the mutations, and are in direct contrast to the results obtained in human cell models . Although, as assessed in the section on ADSL and AdSS, this surprising result might be explained by assuming a peculiar adenine nucleotide metabolism in Drosophila , it is impossible to apply these results to the set‐up of potential therapeutic and dietary interventions that may extend the lifespan and improve the health span of humans.…”

Section: Enzymes Participating In Adenylate Metabolismmentioning

confidence: 81%

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Camici¹,

Allegrini²,

Tozzi³

2018

The FEBS Journal

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Purine nucleotides are involved in a variety of cellular functions, such as energy storage and transfer, and signalling, in addition to being the precursors of nucleic acids and cofactors of many biochemical reactions. They can be generated through two separate pathways, the de novo biosynthesis pathway and the salvage pathway. De novo purine biosynthesis leads to the formation of IMP, from which the adenylate and guanylate pools are generated by two additional steps. The salvage pathways utilize hypoxanthine, guanine and adenine to generate the corresponding mononucleotides. Despite several decades of research on the subject, new and surprising findings on purine metabolism are constantly being reported, and some aspects still need to be elucidated. Recently, purine biosynthesis has been linked to the metabolic pathways regulated by AMP-activated protein kinase (AMPK). AMPK is the master regulator of cellular energy homeostasis, and its activity depends on the AMP : ATP ratio. The cellular energy status and AMPK activation are connected by AMP, an allosteric activator of AMPK. Hence, an indirect strategy to affect AMPK activity would be to target the pathways that generate AMP in the cell. Herein, we report an up-to-date review of the interplay between AMPK and adenylate metabolizing enzymes. Some aspects of inborn errors of purine metabolism are also discussed.

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Section: Enzymes Participating In Adenylate Metabolismmentioning

confidence: 81%

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Camici¹,

Allegrini²,

Tozzi³

2018

The FEBS Journal

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“…A number of previous studies demonstrated that cell cycle arrest and apoptosis may be directly associated (32)(33)(34). For instance, the apoptotic cascade may be inhibited or induced via cell cycle manipulation depending on the cellular circumstance (35).…”

Section: Discussionmentioning

confidence: 99%

Bergapten induces G1 arrest of non‑small cell lung cancer cells, associated with the p53‑mediated cascade

Chiang

Lin

et al. 2019

Mol Med Report

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The pr incipal subtype of lung cancer, non-small cell lung cancer (NSCLC) is a life-threatening malignancy that causes high mortality rates. Bergapten (5-methoxypsoralen) has been identified to possess anticancer activity against a number of carcinomas. In the present study, the effects of bergapten on NSCLC cells were investigated. The cell viability was determined by MTT assay. Cell cycle distribution was analyzed using flow cytometry. Protein expression and kinase cascade were demonstrated using western blot analysis. The results demonstrated that treatment with bergapten (50 µM for 48 h) inhibited the viability of A549 and NCI-H460 NSCLC cells to 79.1±2.8% and 74.5±3.1%, respectively, compared with the controls. It was identified that bergapten induced G1 phase accumulation in A549 and NCI-H460 cells between ~58 and 75% (P<0.01). In addition, bergapten significantly increased the sub-G1 phase ratio to ~9% (P<0.05) in the two cell types. Further investigation demonstrated that bergapten upregulated the expression of cellular tumor antigen p53 (p53) and its downstream proteins cyclin-dependent kinase inhibitor 1 and cyclin-dependent kinase inhibitor 1B, whereas, it downregulated the expression of cyclin D1 and CDK4. Overall, these results suggested that bergapten may inhibit cell viability and trigger G1 arrest and apoptosis in A549 and NCI-H460 cells, which may be attributed to the activation of p53-mediated cascades. Therefore, bergapten may be beneficial for NSCLC treatment.

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“…In addition to energy regulation, AMPK also governs the important cellular physiological activities including cell proliferation, cell growth, and autophagy (18,19). Accordingly, AMPK has been recognized as an important anticancer target in suppressing the growth of different carcinoma cells such as 786-O (10), K562 (11), and HT29 (20). Similarly, we also observe that adenine-induced AMPK activation play an important role in the growth inhibition of HepG2 and SK-Hep-1 cells which express wild-type p53.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous studies have demonstrated that adenine exerts its anticancer activity by activating AMPK and the associating signaling (10,11). As a result, the role of AMPK activation in adenineinduced apoptotic signals in HepG2 cells was then investigated.…”

Section: Adenine Induced Activation Of Ampk To Trigger P53-mediated Amentioning

confidence: 99%

“…For example, adenosine nucleoside plays a pivotal role in governing cell differentiation, cardiac function, and neurotransmission (6)(7)(8). In parallel, adenine, a purine nucleobase, has also shown various bioactivities through adenosine monophosphate-activated protein kinase (AMPK) signaling, including anti-inflammation and anti-cancer activities in our previous studies (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

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Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade

Huang

Chen

et al. 2020

Int. J. Med. Sci.

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Background: Adenine exhibits potential anticancer activity against several types of malignancies. However, whether adenine has anticancer effects on hepatocellular carcinoma (HCC) cells is incompletely explored. Methods: Human HCC cell lines HepG2 and SK-Hep-1 (p53-wild type) and Hep3B (p53-deficient) were used as cell model. Cell growth and cell cycle distribution were determined using MTT assay and flow cytometric analysis, respectively. Protein expression and phosphorylation were assessed by Western blot. Involvement of AMP-activated protein kinase (AMPK) was evaluated using specific inhibitor and small inhibitory RNA (siRNA). Results: Adenine treatments (0.5 -2 mM) clearly decreased the cell growth of Hep G2 and SK-Hep-1 cells to 72.5 ± 3.4% and 71.3 ± 4.6% of control, respectively. In parallel, adenine also induced sub-G1 and S phase accumulation in both HCC cells. However, adenine did not affect the cell growth and cell cycle distribution of Hep3B cell. Western blot analysis showed that adenine reduced expression of cyclin A/D1 and cyclin-dependent kinase (CDK)2 and upregulated p53, p21, Bax, PUMA, and NOXA in HepG2 cell. Moreover, adenine induced AMPK activation that was involved in the p53-associated apoptotic cascade in HepG2 cells. Inhibition of AMPK activation or knockdown of AMPK restored the decreased cell growth of HepG2 and SK-Hep-1 cells in response to adenine. Conclusions: These findings reveal that adenine reduces the cell growth of HepG2 and SK-Hep-1 but not Hep3B cells, attributing to the AMPK/p53-mediated S phase arrest and apoptosis. It suggests that adenine has anticancer potential against p53-wild type HCC cells and may be beneficial as an adjuvant for HCC treatment.

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Adenine causes cell cycle arrest and autophagy of chronic myelogenous leukemia K562 cells via AMP-activated protein kinase signaling

Cited by 10 publications

References 32 publications

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Interplay between adenylate metabolizing enzymes and AMP‐activated protein kinase

Bergapten induces G1 arrest of non‑small cell lung cancer cells, associated with the p53‑mediated cascade

Adenine inhibits growth of hepatocellular carcinoma cells via AMPK-mediated S phase arrest and apoptotic cascade

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