ArticleMolecular biology reports2020
Reactive oxygen species generation and mitochondrial dysfunction for the initiation of apoptotic cell death in human hepatocellular carcinoma HepG2 cells by a cyclic dipeptide Cyclo(-Pro-Tyr).
Article in Molecular biology reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 51 citations in OpenAlex.
- Toxicological Assessment of the Marine-Derived Cyclic Dipeptide Cyclo(Pro-Tyr) Using In Vitro, Zebrafish Embryo, and BALB/c Mouse Models.Journal of xenobiotics · 2026Article
- Synergistic modulation of ABC transporter-mediated multidrug resistance byRSC advances · 2026Article
- A therapeutic approach of LC-MS characterised MFER-Mc against alcohol and NDEA induced hepatocellular carcinoma activity through LXR-α, LXR-β and HMG-CoA pathway: an in-silico, in-vitro and in-vivo study.Medical oncology (Northwood, London, England) · 2025Article
- Development and Evaluation of Indian Mustard Honey-Loaded Fast Dissolving PVA/AG Nanofibers for Enhanced Neuroprotection.ACS omega · 2025Article
- Progress in Preparation Technology and Functional Research On Marine Bioactive Peptides.Marine biotechnology (New York, N.Y.) · 2025Review
- Article
- The Suppression of Signal Transducer and Activator of Transcription-3 in A549 human Lung Carcinoma Cells Induced by Marine SpongeJournal of experimental pharmacology · 2025Article
- Antimicrobial Cyclic Dipeptides from Japanese Quail (Journal of microbiology and biotechnology · 2024Article
- From Beach to the Bedside: Harnessing Mitochondrial Function in Human Diseases Using New Marine-Derived Strategies.International journal of molecular sciences · 2024Review
- Development and Challenges of Cyclic Peptides for Immunomodulation.Current protein & peptide science · 2024Review
- Article
- Aquatic Peptide: The Potential Anti-Cancer and Anti-Microbial Activity of GE18 Derived from Pathogenic FungusMolecules (Basel, Switzerland) · 2023Article
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- Anti-Cancer and Anti-Inflammatory Activities of a Short Molecule, PS14 Derived from the Virulent Cellulose Binding Domain ofMolecules (Basel, Switzerland) · 2022Article
- Analysis of the Antioxidant Composition of Low Molecular Weight Metabolites from the Agarolytic BacteriumAntioxidants (Basel, Switzerland) · 2022Article
- Marine Compounds, Mitochondria, and Malignancy: A Therapeutic Nexus.Marine drugs · 2022Review
- Antitumor Effects of a Sesquiterpene Derivative from Marine Sponge in Human Breast Cancer Cells.Marine drugs · 2021Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Cyclic dipeptides are increasingly gaining importance as considering its significant biological and pharmacological activities. This study was aimed to investigate the anticancer activity of a dipeptide Cyclo(-Pro-Tyr) (DP) identified from marine sponge Callyspongia fistularis symbiont Bacillus pumilus AMK1 and the underlying apoptotic mechanisms in the liver cancer HepG2 cell lines. MTT assay was done to demonstrate the cytotoxic effect of DP in HepG2 cells and mouse Fibroblast McCoy cells. Initially, apoptosis inducing activity of DP was identified using propidium iodide (PI) and acridine orange/ethidium bromide (AO/EB) dual staining, then it was confirmed by DNA fragmentation assay and western blotting analysis of apoptosis related markers Bax, Bcl-2, cytochrome c, caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). Rhodamine 123 staining was performed to observe DP effects on the mitochondrial membrane potential (MMP) and DCFH-DA (Dichloro-dihydro-fluorescein diacetate) staining was done to measure the intracellular reactive oxygen species (ROS) levels. The MTT results revealed that DP initiated dose-dependent cytotoxicity in HepG2 cells, but no significant toxicity in mouse Fibroblast McCoy cells treated with DP at the specified concentrations. DP induced apoptosis, which is confirmed by the appearance of apoptotic bodies with PI and AO/EB dual staining, and DNA fragmentation. DP significantly elevated the Bax/Bcl-2 ratio, disrupted the mitochondrial membrane potential (MMP), enhanced cytochrome c release from mitochondria, increased caspase-3 activation, the cleavage of PARP and increased intracellular reactive oxygen species (ROS) levels. Besides this, DP successfully inhibited the phosphorylation of PI3K, AKT and increased PTEN expression. These results suggested DP might have anti-cancer effect by initiating apoptosis through mitochondrial dysfunction and downregulating PI3K/Akt signaling pathway in HepG2 cells with no toxicity effect on normal fibroblast cells. Therefore, DP may be developed as a potential alternative therapeutic agent for treating hepatocellular carcinoma.
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