Background: Tocotrienols, especially the gamma isomer was discovered to possess cytotoxic effects associated with the induction of apoptosis in numerous cancers. Individual tocotrienol isomers are believed to induce dissimilar apoptotic mechanisms in different cancer types. This study was aimed to compare the cytotoxic potency of alpha-, gamma- and delta-tocotrienols, and to explore their resultant apoptotic mechanisms in human lung adenocarcinoma A549 and glioblastoma U87MG cells which are scarcely researched.
Methods: The cytotoxic effects of alpha-, gamma- and delta-tocotrienols in both A549 and U87MG cancer cells were first determined at the cell viability and morphological aspects. DNA damage types were then identified by comet assay and flow cytometric study was carried out to support the incidence of apoptosis. The involvements of caspase-8, Bid, Bax and mitochondrial membrane permeability (MMP) in the execution of apoptosis were further expounded.
Results: All tocotrienols inhibited the growth of A549 and U87MG cancer cells in a concentration- and time-dependent manner. These treated cancer cells demonstrated some hallmarks of apoptotic morphologies, apoptosis was further confirmed by cell accumulation at the pre-G1 stage. All tocotrienols induced only double strand DNA breaks (DSBs) and no single strand DNA breaks (SSBs) in both treated cancer cells. Activation of caspase-8 leading to increased levels of Bid and Bax as well as cytochrome c release attributed by the disruption of mitochondrial membrane permeability in both A549 and U87MG cells were evident.
Conclusions: This study has shown that delta-tocotrienol, in all experimental approaches, possessed a higher efficacy (shorter induction period) and effectiveness (higher induction rate) in the execution of apoptosis in both A549 and U87MG cancer cells as compared to alpha- and gamma-tocotrienols. Tocotrienols in particular the delta isomer can be an alternative chemotherapeutic agent for treating lung and brain cancers.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4295404 | PMC |
| http://dx.doi.org/10.1186/1472-6882-14-469 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In Vitro and In Vivo Anticancer Activities of Water-Soluble Ru(II)(η6--cymene) Complexes via Activating Apoptosis Central Regulators and Possibilities of New Antitumor Strategies in Triple Negative Breast Cancers.
J Med Chem
January 2025
Inner Mongolia Key Laboratory for Molecular Regulation of the Cell, Inner Mongolia University, Hohhot 010021, People's Republic of China.
In this study, we synthesized 12 monofunctional tridentate ONS-donor salicylaldimine ligand ()-based Ru(II) complexes with general formula [(Ru()(-cymene)]·Cl (-), characterized by H NMR, C NMR, UV, FT-IR spectroscopy, HR-ESI mass spectrometry, and single-crystal X-ray analysis showing ligand's orientation around the Ru(II) center. All 12 of these 12 complexes were tested for their anticancer activities in multiple cancer cells. The superior antitumor efficacy of , , and was demonstrated by reduced mitochondrial membrane potential, impaired proliferative capacity, and disrupted redox homeostasis, along with enhanced apoptosis through caspase-3 activation and downregulation of Bcl-2 expression.
View Article and Find Full Text PDFIGF2BP3 is upregulated in endometrial cancer and tightly regulates the growth of drug-resistant endometrial cancer cells via HMGA1.
Sci Prog
January 2025
Department of Obstetrics and Gynecology, Hebei Medical University Third Hospital, Shijiazhuang, China.
Objective: Endometrial cancer (EC) is a malignant tumor with various histological subtypes and molecular phenotypes. The evaluation of drug resistance is important for cancer treatment. Progesterone resistance is the major challenge in EC.
View Article and Find Full Text PDFDesign, Synthesis and Anti-Inflammatory Evaluation of 3-Substituted 5-Amidobenzoate Derivatives as Novel P2Y Receptor Antagonists via Structure-Guided Molecular Hybridization.
J Med Chem
January 2025
College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
The P2YR is activated by UDP and UDP glucose and is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2YR antagonists and the crystallographic overlap study between PPTN and compound , a series of 3-substituted 5-amidobenzoate derivatives were designed, synthesized, and identified as promising P2YR antagonists. The optimal compound (methyl 3-(1-benzo[]imidazol-2-yl)-5-(2-(-tolyl) acetamido)benzoate, IC = 0.
View Article and Find Full Text PDFSophoricoside Inhibited Glioblastoma Cell Progression Through Activated AMP-Activated Protein Kinase (AMPK).
Mol Carcinog
January 2025
Department of Neurosurgery, Huanggang Central Hospital of Yangtze University, Huanggang, China.
Glioblastoma (GBM) is the most common malignant primary brain tumor, with a mean survival of less than 2 years. Unique brain structures and the microenvironment, including blood-brain barriers, put great challenges on clinical drug development. Sophoricoside (Sop), an isoflavone glycoside isolated from seeds of Sophora japonica L.
View Article and Find Full Text PDFMechanistic understanding of pH as a driving force in cancer therapeutics.
J Mater Chem B
January 2025
Department of Forensic Science, School for Bio Engineering and Bio Sciences, Lovely Professional University, Phagwara, Punjab, India.
The development of pH-directed nanoparticles for tumor targeting represents a significant advancement in cancer biology and therapeutic strategies. These innovative materials have the ability to interact with the unique acidic microenvironment of tumors. They enhance drug delivery, increase therapeutic efficacy, and reduce systemic toxicity.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!