Subject    :    [2015 Dec;39(6)] Metformin Promotes Apoptosis but Suppresses Autophagy in Glucose-Deprived H4IIE Hepatocellular Carcinoma Cells
Writer KDA
Date 2016-01-07 15:55:49 Hit 6,566
Diabetes Metab J. 2015 Dec;39(6):518-527. English. Published online Dec 11, 2015.  http://dx.doi.org/10.4093/dmj.2015.39.6.518 
Copyright © 2015 Korean Diabetes Association
   
Metformin Promotes Apoptosis but Suppresses Autophagy in Glucose-Deprived H4IIE Hepatocellular Carcinoma Cells
Deok-Bae Park
Department of Histology and Institute of Medical Science, Jeju National University School of Medicine, Jeju, Korea.
Corresponding author: Deok-Bae Park. Department of Histology and Institute of Medical Science, Jeju National University School of Medicine, 102 Jejudaehang-ro, Jeju 54987, Korea. Email:parkdb@jejunu.ac.kr 
 
Received November 17, 2014; Accepted February 26, 2015.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

 
Abstract
Background

Metformin, a well-known anti-diabetic drug, has gained interest due to its association with the reduction of the prevalence of cancer in patients with type 2 diabetes and the anti-proliferative effect of metformin in several cancer cells. Here, we investigated the anti-proliferative effect of metformin with respect to apoptosis and autophagy in H4IIE hepatocellular carcinoma cells.

Methods

H4IIE rat cells were treated with metformin in glucose-free medium for 24 hours and were then subjected to experiments examining the onset of apoptosis and/or autophagy as well as the related signaling pathways.

Results

When H4IIE cells were incubated in glucose-free media for 24 hours, metformin and 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) reduced the viability of cells. Inhibition of AMP-activated protein kinase (AMPK) by compound C significantly blocked cell death induced by metformin or AICAR. Pro-apoptotic events (nuclear condensation, hydrolysis of intact poly ADP ribose polymerase and caspase-3) were stimulated by metformin and then suppressed by compound C. Interestingly, the formation of acidic intracellular vesicles, a marker of autophagy, was stimulated by compound C. Although the deprivation of amino acids in culture media also induced apoptosis, neither metformin nor compound C affected cell viability. The expression levels of all of the autophagy-related proteins examined decreased with metformin, and two proteins (light chain 3 and beclin-1) were sensitive to compound C. Among the tested inhibitors against MAP kinases and phosphatidylinositol-3-kinase/mammalian target of rapamycin, SB202190 (against p38MAP kinase) significantly interrupted the effects of metformin.

Conclusion

Our data suggest that metformin induces apoptosis, but suppresses autophagy, in hepatocellular carcinoma cells via signaling pathways, including AMPK and p38 mitogen-activated protein kinase.

   

Keywords: Apoptosis; Autophagy; H4IIE hepatocellular carcinoma cells; Metformin

Articles - Reviews in DMJ
No. Subject Date Hit ↑
Notice : [2019 Aug;43(4)] Glycosylated Hemoglobin in Subjects Affected by Iron-Deficiency Anemia [2019 Aug;43(4)] Glycosylated Hemoglobin in Subjects Affected by Iro... 2019-10-10 289
Notice : [2019 Aug;43(4)] Impact of Longitudinal Changes in Metabolic Syndrome Status over 2 Years on 10-Year Incident Diabetes Mellitus [2019 Aug;43(4)] Impact of Longitudinal Changes in Metabolic Syndrom... 2019-10-10 285
Notice : [2019 Aug;43(4)] Increased Serum Angiopoietin-Like 6 Ahead of Metabolic Syndrome in a Prospective Cohort Study [2019 Aug;43(4)] Increased Serum Angiopoietin-Like 6 Ahead of Metabo... 2019-10-10 298
Notice : [2019 Aug;43(4)] The Protective Effects of Increasing Serum Uric Acid Level on Development of Metabolic Syndrome [2019 Aug;43(4)] The Protective Effects of Increasing Serum Uric Aci... 2019-10-10 284
Notice : [2019 Aug;43(4)] Factors Related to Blood Intact Incretin Levels in Patients with Type 2 Diabetes Mellitus [2019 Aug;43(4)] Factors Related to Blood Intact Incretin Levels in ... 2019-10-10 285
Notice : [2019 Aug;43(4)] Diabetes Fact Sheets in Korea, 2018: An Appraisal of Current Status [2019 Aug;43(4)] Diabetes Fact Sheets in Korea, 2018: An Appraisal o... 2019-10-10 279
Notice : [2019 Aug;43(4)] Plasma Fetuin-A Levels and Risk of Type 2 Diabetes Mellitus in A Chinese Population: A Nested Case-Control Study [2019 Aug;43(4)] Plasma Fetuin-A Levels and Risk of Type 2 Diabetes ... 2019-10-10 282
Notice : [2019 Aug;43(4)] Lower Leg Fat Depots Are Associated with Albuminuria Independently of Obesity, Insulin Resistance, and Metabolic Syndrome (Korea National Health and Nutrition Examination Surveys 2008 to 2011) [2019 Aug;43(4)] Lower Leg Fat Depots Are Associated with Albuminuri... 2019-10-10 289
Notice : [2019 Aug;43(4)] Association between Serum Selenium Level and the Presence of Diabetes Mellitus: A Meta-Analysis of Observational Studies [2019 Aug;43(4)] Association between Serum Selenium Level and the Pr... 2019-10-10 278
Notice : [2019 Aug;43(4)] Effectiveness and Safety of Adding Basal Insulin Glargine in Patients with Type 2 Diabetes Mellitus Exhibiting Inadequate Response to Metformin and DPP-4 Inhibitors with or without Sulfonylurea [2019 Aug;43(4)] Effectiveness and Safety of Adding Basal Insulin Gl... 2019-10-10 273
Notice : [2019 Aug;43(4)] Additional Effect of Dietary Fiber in Patients with Type 2 Diabetes Mellitus Using Metformin and Sulfonylurea: An Open-Label, Pilot Trial [2019 Aug;43(4)] Additional Effect of Dietary Fiber in Patients with... 2019-10-10 283
Notice : [2019 Aug;43(4)] Asian Subpopulations May Exhibit Greater Cardiovascular Benefit from Long-Acting Glucagon-Like Peptide 1 Receptor Agonists: A Meta-Analysis of Cardiovascular Outcome Trials [2019 Aug;43(4)] Asian Subpopulations May Exhibit Greater Cardiovasc... 2019-10-10 277
Notice : [2019 Aug;43(4)] 2019 Clinical Practice Guidelines for Type 2 Diabetes Mellitus in Korea [2019 Aug;43(4)] 2019 Clinical Practice Guidelines for Type 2 Diabet... 2019-10-10 274
Notice : [2019 Aug;43(4)] Continuous Glucose Monitoring Sensors for Diabetes Management: A Review of Technologies and Applications [2019 Aug;43(4)] Continuous Glucose Monitoring Sensors for Diabetes ... 2019-10-10 275
Notice : [2019 June;43(3)] Serum R-Spondin 1 Is a New Surrogate Marker for Obesity and Insulin Resistance [2019 June;43(3)] Serum R-Spondin 1 Is a New Surrogate Marker for Ob... 2019-06-28 1,530
Notice : [2019 June;43(3)] Association of Visit-to-Visit Variability of Blood Pressure with Cardiovascular Disease among Type 2 Diabetes Mellitus Patients: A Cohort Study [2019 June;43(3)] Association of Visit-to-Visit Variability of Blood... 2019-06-28 1,677
Notice : [2019 June;43(3)]  Oral Glucose Tolerance Testing Allows Better Prediction of Diabetes in Women with a History of Gestational Diabetes Mellitus [2019 June;43(3)] Oral Glucose Tolerance Testing Allows Better Pred... 2019-06-28 1,535
Notice : [2019 June;43(3)] Diabetes Mellitus and Cause-Specific Mortality: A Population-Based Study [2019 June;43(3)] Diabetes Mellitus and Cause-Specific Mortality: A ... 2019-06-28 1,520
Notice : [2019 June;43(3)]  Effectiveness of Exercise Intervention in Reducing Body Weight and Glycosylated Hemoglobin Levels in Patients with Type 2 Diabetes Mellitus in Korea: A Systematic Review and Meta-Analysis [2019 June;43(3)] Effectiveness of Exercise Intervention in Reducin... 2019-06-28 1,480
Notice : [2019 June;43(3)] Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study [2019 June;43(3)] Acarbose Add-on Therapy in Patients with Type 2 Di... 2019-06-28 1,908
Notice : [2019 June;43(3)] Efficacy and Safety of Voglibose Plus Metformin in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Trial [2019 June;43(3)] Efficacy and Safety of Voglibose Plus Metformin in... 2019-06-28 1,487
Notice : [2019 June;43(3)] Understanding Bile Acid Signaling in Diabetes: From Pathophysiology to Therapeutic Targets [2019 June;43(3)] Understanding Bile Acid Signaling in Diabetes: Fro... 2019-06-28 1,468
Notice : [2019 June;43(3)] Mitochondrial Dysfunction in Adipocytes as a Primary Cause of Adipose Tissue Inflammation [2019 June;43(3)] Mitochondrial Dysfunction in Adipocytes as a Prima... 2019-06-18 1,740
262 [2016 Dec;40(6)] Reduction of Sulfonylurea with the Initiation of Ba... 2017-01-02 6,767
261 [2016 Dec;40(6)] Risk Factors and Adverse Outcomes of Severe Hypogly... 2017-01-02 6,760
260 [2015 Dec;39(6)] Metformin Promotes Apoptosis but Suppresses Autopha... 2016-01-07 6,566
259 [2015 Oct;39(5)] Identification of Two Cases of Ciliopathy-Associate... 2015-12-08 6,520
258 [2015 Dec;39(6)] Maturity-Onset Diabetes of the Young: What Do Clini... 2016-01-07 6,516
257 [2015 Dec;39(6)] Non-Association between rs7903146 and rs12255372 Po... 2016-01-07 6,429
256 [2015 Oct;39(5)] The Association between Hypertension Comorbidity an... 2015-12-08 6,428
255 [2015 Dec;39(6)] Cardiovascular Disease Predicts Severe Hypoglycemia... 2016-01-07 6,413
254 [2015 Oct;39(5)] Perspective of Small-Molecule AdipoR Agonist for Ty... 2015-12-08 6,350
253 [2015 Dec;39(6)] Autophagy: A Novel Therapeutic Target for Diabetic ... 2016-01-07 6,332

목록

Gets the previous 5 pages.   Go to previous page.  1   2   3   [4]   5     Go to next page. Gets the next  5 pages.