ArticleCancer science2015
Activation of AMP-activated protein kinase by retinoic acid sensitizes hepatocellular carcinoma cells to apoptosis induced by sorafenib.
Article in Cancer science, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Putative molecular targets for vitamin A in neutralizing oxidative stress in acute and chronic pancreatitis - a systematic review.Naunyn-Schmiedeberg's archives of pharmacology · 2023Pooled it
- Serum Retinol and Risk of Overall and Site-Specific Cancer in the ATBC Study.American journal of epidemiology · 2020Trial
- Metabolic sensor AMPK licenses intestinal CD103Science advances · 2026Article
- Psammaplysene D overcomes sorafenib resistance in liver cancer by targeting FGFR4/CYP26A1-retinoic acid axis to drive ferroptosis.Journal of experimental & clinical cancer research : CR · 2026Article
- Article
- Combination of cellular retinoic acid-binding protein 2 overexpression and all-trans retinoic acid synergistically inhibits oesophageal squamous cell carcinoma progression.Discover oncology · 2025Article
- Retinoic Acid-Mediated Control of Energy Metabolism Is Essential for Lung Branching Morphogenesis.International journal of molecular sciences · 2024Article
- SIRT1 as a potential key regulator for mediating apoptosis in oropharyngeal cancer using cyclophosphamide and all-trans retinoic acid.Scientific reports · 2024Article
- A Novel Combinatorial Regimen Using Sorafenib and Uttroside B, A US FDA-designated 'Orphan Drug', for the Treatment of Hepatocellular Carcinoma.Anti-cancer agents in medicinal chemistry · 2024Article
- Breaking the Barriers of Therapy Resistance: Harnessing Ferroptosis for Effective Hepatocellular Carcinoma Therapy.Journal of hepatocellular carcinoma · 2024Review
- Potential antitumour effect of all-trans retinoic acid on regorafenib-treated human colon cancer cell lines.Contemporary oncology (Poznan, Poland) · 2023Article
- Intracellular alpha-fetoprotein interferes with all-trans retinoic acid induced ATG7 expression and autophagy in hepatocellular carcinoma cells.Scientific reports · 2021Article
- Carotenoids in Cancer Apoptosis-The RoadCancers · 2020Review
- Adiponectin and Cognitive Decline.International journal of molecular sciences · 2020Review
- LncRNA NBR2 Inhibits the Malignancy of Thyroid Cancer, Associated With Enhancing the AMPK Signaling.Frontiers in oncology · 2020Article
- Is the era of sorafenib over? A review of the literature.Therapeutic advances in medical oncology · 2020Review
- Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Is Reversed by SIRT1.International journal of molecular sciences · 2019Article
- Single-Cell Analysis Reveals Regional Reprogramming During Adaptation to Massive Small Bowel Resection in Mice.Cellular and molecular gastroenterology and hepatology · 2019Article
- All-Frontiers in pharmacology · 2019Article
- Sestrin 2 confers primary resistance to sorafenib by simultaneously activating AKT and AMPK in hepatocellular carcinoma.Cancer medicine · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To improve the outcome of cancer chemotherapy, strategies to enhance the efficacy of anticancer drugs are required. Sorafenib is the only drug to prolong overall survival of the patients with hepatocellular carcinoma (HCC), however, the outcome is still not satisfactory. Retinoids, vitamin A derivatives, have been known to exhibit inhibitory effects on various cancers including HCC. In this study, we investigated the effects of combined treatment using sorafenib and retinoids including all-trans retinoic acid (ATRA), NIK-333, and Am80 on HCC cells. Cell viability assays in six HCC cell lines, HepG2, PLC/PRF/5, HuH6, HLE, HLF, and Hep3B, revealed that 5 and 10 μM ATRA, concentrations that do not exert cytotoxic effects, enhanced the cytotoxicity of sorafenib, being much more effective than NIK-333 and Am80. We found that ATRA induced AMP-activated protein kinase activation, which was followed by reduced intracellular ATP level. Gene expression analysis revealed that ATRA decreased the expression of glycolytic genes such as GLUT-1 and LDHA. In the combination treatment using ATRA and sorafenib, increased apoptosis, followed by the activation of p38 MAPK and JNK, the upregulation and translocation of Bax to mitochondria, and the activation of caspase-3, was observed. Suppression of AMP-activated protein kinase by siRNA restored the viability of the cells treated with ATRA and sorafenib. Our results thus indicate that ATRA is useful for enhancing the cytotoxicity of sorafenib against HCC cells by regulating the energy metabolism of HCC cells.
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