Expression of p21Waf1/Cip1 and Cyclin D1 Is Increased in Butyrate-resistant HeLa Cells

Derjuga, Anna; Richard, Caroline; Crosato, Milena; Wright, Paul S.; Chalifour, Lorraine E.; Valdez, J.G.; Barraso, A; Crissman, Harry A.; Nishioka, Walter K.; Bradbury, E. Morton; Th'ng, John P.H.

doi:10.1074/jbc.m104735200

Cited by 15 publications

(3 citation statements)

References 47 publications

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“…Upregulation of cyclin D1 and downregulation of p21 and Bax are also involved in BR human CRC cells, HCT116, HT29 and SW480 [ 35 ]. HeLa human cervical cancer cells have also been reported to develop resistance to butyrate via upregulation of cyclin D1 [ 43 ]. Tamoxifen-resistant breast cancer cells, MCF7 and T47D, have been reported to overexpress cyclin D1 owing to the inhibition of cyclin D1 degradation [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Role of AMPK in Regulation of Oxaliplatin-Resistant Human Colorectal Cancer

et al. 2022

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Oxaliplatin is a platinum analog that can interfere with DNA replication and transcription. Continuous exposure to oxaliplatin results in chemoresistance; however, this mechanism is not well known. In this study, oxaliplatin-resistant (OR) colorectal cancer (CRC) cells of HCT116, HT29, SW480 and SW620 were established by gradually increasing the drug concentration to 2.5 µM. The inhibitory concentrations of cell growth by 50% (IC50) of oxaliplatin were 4.40–12.7-fold significantly higher in OR CRC cells as compared to their respective parental (PT) CRC cells. Phospho-Akt and phospho-mammalian target of rapamycin (mTOR) decreased in PT CRC cells but was overexpressed in OR CRC cells in response to oxaliplatin. In addition, an oxaliplatin-mediated decrease in phospho-AMP-activated protein kinase (AMPK) in PT CRC cells induced autophagy. Contrastingly, an increased phospho-AMPK in OR CRC cells was accompanied by a decrease in LC3B, further inducing the activity of glycolytic enzymes, such as glucose transporter 1 (GLUT1), 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) and phosphofructokinase 1 (PFK1), to mediate cell survival. Inhibition of AMPK in OR CRC cells induced autophagy through inactivation of Akt/mTOR pathway and a decrease in GLUT1, PFKFB3, and PFK1. Collectively, targeting AMPK may provide solutions to overcome chemoresistance in OR CRC cells and restore chemosensitivity to anticancer drugs.

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Section: Discussionmentioning

confidence: 99%

Role of AMPK in Regulation of Oxaliplatin-Resistant Human Colorectal Cancer

et al. 2022

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“…Activation of Bcl-2 is also involved in protective autophagy in cancer stem cells via EGFR signaling [ 30 , 31 ]. HeLa human cervical cancer cells also show resistance to butyrate via upregulation of cyclin D1 [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…However, when colon cancer cells are continuously exposed to butyrate, anticancer activity is lost as the cells become resistant to butyrate [ 17 , 18 ] and eventually become resistant to butyrate [ 18 ]. BCS-TC2 human colon adenocarcinoma cells [ 19 ] and HeLa human cervical cancer cells [ 20 ] also showed resistance to butyrate.…”

Section: Introductionmentioning

confidence: 99%

Regulation of Butyrate-Induced Resistance through AMPK Signaling Pathway in Human Colon Cancer Cells

et al. 2021

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Butyrates inhibit cell growth in colon cancer cells by inhibiting histone deacetylases. However, chronic exposure to butyrates induces butyrate resistance in colon cancer cells. The mechanism underlying the acquisition of resistance is not yet fully understood. Here, butyrate-resistant (BR) colon cancer cells were developed in HCT116, HT29, and SW480 human colon cancer cells and were confirmed by the increase in the inhibitory concentrations of cell growth by 50% (IC50) compared to their respective parental (PT) cells. Chronic exposure to butyrate induced autophagy via higher expression of Beclin-1 and LC3B-II. The AMP-activated protein kinase (AMPK) was downregulated along with the activation of Akt and mammalian target of rapamycin (mTOR) and decrease in acetyl-CoA carboxylase (ACC) in BR colon cancer cells compared to those in their respective PT cells. Activation of AMPK by AICAR treatment in BR colon cancer cells suppressed cell proliferation by inhibiting Akt and mTOR and activating ACC. Taken together, chronic exposure to butyrate increased butyrate resistance in human colon cancer by inducing protective autophagy through the downregulation of AMPK/ACC and activation of Akt/mTOR signaling. Activation of AMPK restored sensitivity to butyrate by the inhibition of Akt/mTOR, suggesting that AMPK could be a therapeutic target for BR colon cancers.

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Involvement of the tumor necrosis factor (TNF)/TNF receptor system in leukemic cell apoptosis induced by histone deacetylase inhibitor depsipeptide (FK228)

Sutheesophon

Nishimura

Kobayashi

et al. 2004

Journal Cellular Physiology

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Inhibition of histone deacetylase (HDAC) is a novel strategy for the treatment of leukemias via restoration of aberrantly silenced genes. In this study, we conducted a detailed analysis of anti-leukemic effects of an HDAC inhibitor (HDI), depsipeptide (FK228), using myeloid leukemia cell lines HL-60 and K562. DNA chip analysis revealed upregulation of TNF-alpha mRNA and a number of molecules involved in TNF-signaling such as TRAF-6, caspases-10, and -7 in depsipeptide-treated HL-60 cells, which prompted us to examine the involvement of the TNF/TNF receptor system in the anti-leukemic effects of the drug. Upregulation of TNF-alpha was induced by depsipeptide in HL-60 and K562 cells, which expressed type I TNF receptors (TNF-RI). Depsipeptide activated caspases-8 and -10, which in turn cleave caspases-3 and -7, leading to apoptotic cell death in both cell lines. Anti-TNF-alpha neutralizing antibody and short interfering RNA (siRNA) against TNF-RI alleviated the activation of the caspase cascade and the induction of apoptosis, indicating the presence of an autocrine loop. Finally, we demonstrated that the enhanced production of TNF-alpha by depsipeptide was due to transcriptional activation of the TNF-alpha gene through hyperacetylation of histones H3 and H4 in its promoter region (-208 to +35). These results suggest that autocrine production of TNF-alpha plays a role in the cytotoxicity of depsipeptide against a subset of leukemias.

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Expression of p21Waf1/Cip1 and Cyclin D1 Is Increased in Butyrate-resistant HeLa Cells

Cited by 15 publications

References 47 publications

Role of AMPK in Regulation of Oxaliplatin-Resistant Human Colorectal Cancer

Role of AMPK in Regulation of Oxaliplatin-Resistant Human Colorectal Cancer

Regulation of Butyrate-Induced Resistance through AMPK Signaling Pathway in Human Colon Cancer Cells

Involvement of the tumor necrosis factor (TNF)/TNF receptor system in leukemic cell apoptosis induced by histone deacetylase inhibitor depsipeptide (FK228)

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