ArticleMolecular and cellular biochemistry2015
Downregulation of PI3-K/Akt/PTEN pathway and activation of mitochondrial intrinsic apoptosis by Diclofenac and Curcumin in colon cancer.
Article in Molecular and cellular biochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
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- Advances in Diclofenac Derivatives: Exploring Carborane-Substituted N-Methyl and Nitrile Analogs for Anticancer Therapy.ChemMedChem · 2025Article
- Synthesis and antitumor evaluation of amino acid conjugates of monocarbonyl curcumin in hepatocellular carcinoma cell.Scientific reports · 2025Article
- Prominent Naturally Derived Oxidative-Stress-Targeting Drugs and Their Applications in Cancer Treatment.Antioxidants (Basel, Switzerland) · 2025Review
- Discovery of Novel Mono-Carbonyl Curcumin Derivatives as Potential Anti-Hepatoma Agents.Molecules (Basel, Switzerland) · 2023Article
- Resveratrol and Its Role in the Management of B-Cell Malignancies-A Recent Update.Biomedicines · 2023Review
- Curcumin Nanodiscs Improve Solubility and Serve as Radiological Protectants against Ionizing Radiation Exposures in a Cell-Cycle Dependent Manner.Nanomaterials (Basel, Switzerland) · 2022Article
- Combination Therapy Using Polyphenols: An Efficient Way to Improve Antitumoral Activity and Reduce Resistance.International journal of molecular sciences · 2022Review
- Unboxing the molecular modalities of mutagens in cancer.Environmental science and pollution research international · 2022Review
- Design, Synthesis, and Antitumor Evaluation of Novel Mono-Carbonyl Curcumin Analogs in Hepatocellular Carcinoma Cell.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Can dietary flavonoids be useful in the personalized treatment of colorectal cancer?World journal of gastrointestinal oncology · 2022Review
- Berberine protects against diclofenac sodium-induced testicular impairment in mice by its anti-oxidant and anti-apoptotic activities.Iranian journal of basic medical sciences · 2022Article
- Curcumin induces apoptosis through caspase dependent pathway in human colon carcinoma cells.Molecular biology reports · 2022Article
- Curcumin against gastrointestinal cancer: A review of the pharmacological mechanisms underlying its antitumor activity.Frontiers in pharmacology · 2022Review
- Cadmium induces the thymus apoptosis of pigs through ROS-dependent PTEN/PI3K/AKT signaling pathway.Environmental science and pollution research international · 2021Article
- Anti-cancer properties ofIranian journal of basic medical sciences · 2020Article
- Turmeric and Its Major Compound Curcumin on Health: Bioactive Effects and Safety Profiles for Food, Pharmaceutical, Biotechnological and Medicinal Applications.Frontiers in pharmacology · 2020Review
- Curcumin inhibits proliferation of hepatocellular carcinoma cells through down regulation of DJ-1.Cancer biomarkers : section A of Disease markers · 2020Article
- Edaravone reduces oxidative stress and intestinal cell apoptosis after burn through up-regulating miR-320 expression.Molecular medicine (Cambridge, Mass.) · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphatidylinositol 3-kinase (PI3-K)/PTEN/Akt signaling is over activated in various tumors including colon cancer. Activation of this pathway regulates multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth that underlie the biology of a cancer cell. In the present study, the chemopreventive effects have been observed of Diclofenac, a preferential COX-2 inhibitory non-steroidal anti-inflammatory drugs, and Curcumin, a natural anti-inflammatory agent, in the early stage of colorectal carcinogenesis induced by 1,2-dimethylhydrazine dihydrochloride in rats. The tumor-promoting role of PI3-K/Akt/PTEN signal transduction pathway and its association with anti-apoptotic family of proteins are also observed. Both Diclofenac and Curcumin downregulated the PI3-K and Akt expression while promoting the apoptotic mechanism. Diclofenac and Curcumin administration significantly increased the expression of pro-apoptotic Bcl-2 family members (Bad and Bax) while decreasing the anti-apoptotic Bcl-2 protein. An up-regulation of cysteine protease family apoptosis executioner, such as caspase-3 and -9, is seen. Diclofenac and Curcumin inhibited the Bcl-2 protein by directly interacting at the active site by multiple hydrogen bonding, as also evident by negative glide score of Bcl-2. These drugs stimulated apoptosis by increasing reactive oxygen species (ROS) generation and simultaneously decreasing the mitochondrial membrane potential (ΔΨ M). Diclofenac and Curcumin showed anti-neoplastic effects by downregulating PI3-K/Akt/PTEN pathway, inducing apoptosis, increasing ROS generation, and decreasing ΔΨ M. The anti-neoplastic and apoptotic effects were found enhanced when both Diclofenac and Curcumin were administered together, rather than individually.
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