ArticleInternational journal of molecular sciences2022
PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer.
Article in International journal of molecular sciences, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 46 citations in OpenAlex.
- Ascorbate-driven quinone redox cycling as a pro-oxidant anticancer strategy.Redox biology · 2026Review
- ALKBH2 promotes the Warburg effect and bladder cancer progression under hypoxic conditions via the PI3K/AKT pathway.Clinical and experimental medicine · 2026Article
- ATR-FTIR spectroscopy combined with chemometrics reveals molecular alterations and anticancer effects of Nigella sativa extract in human colon cancer cells.Scientific reports · 2026Article
- Article
- Anticancer effects of thymoquinone on prostate cancer cells and natural killer cell activity.Oncology letters · 2025Article
- The Inositol-5-Phosphatase SHIP1: Expression, Regulation and Role in Acute Lymphoblastic Leukemia.International journal of molecular sciences · 2025Review
- Promotion of Autophagy and Apoptosis in Colorectal Cancer Exposed to Imatinib and Thymoquinone.Journal of biochemical and molecular toxicology · 2025Article
- Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation.Journal of the Egyptian National Cancer Institute · 2025Article
- Exploring the antiproliferative effect of PI3K/Akt/mTOR pathway and CDK4/6 inhibitors in human papillomavirus‑positive and ‑negative head and neck squamous cell carcinoma cell lines.International journal of oncology · 2025Article
- Molecular Mechanisms of Dietary Compounds in Cancer Stem Cells from Solid Tumors: Insights into Colorectal, Breast, and Prostate Cancer.International journal of molecular sciences · 2025Review
- Identification of anoikis-related genes to develop a risk model and predict the prognosis and tumor microenvironment in rectal adenocarcinoma.Frontiers in genetics · 2025Article
- Molecular Mechanisms and Signaling Pathways Underlying the Therapeutic Potential of Thymoquinone Against Colorectal Cancer.Molecules (Basel, Switzerland) · 2024Review
- Natural Products and Derivatives Targeting Metabolic Reprogramming in Colorectal Cancer: A Comprehensive Review.Metabolites · 2024Review
- SMAD4 inhibits glycolysis in ovarian cancer through PI3K/AKT/HK2 signaling pathway by activating ARHGAP10.Cancer reports (Hoboken, N.J.) · 2024Article
- Article
- The Critical Function of microRNAs in Developing Resistance against 5- Fluorouracil in Cancer Cells.Mini reviews in medicinal chemistry · 2024Review
- Nano-based formulations of thymoquinone are new approaches for psoriasis treatment: a literature review.Frontiers in immunology · 2024Review
- Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer.Cancer cell international · 2023Review
- Targeting PI3K/Akt signaling in prostate cancer therapy.Journal of cell communication and signaling · 2023Review
- The Antiproliferative Activity ofMolecules (Basel, Switzerland) · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Colorectal cancer (CRC) is the third leading cause of death in men and the fourth in women worldwide and is characterized by deranged cellular energetics. Thymoquinone, an active component from Nigella sativa, has been extensively studied against cancer, however, its role in affecting deregulated cancer metabolism is largely unknown. Further, the phosphoinositide 3-kinase (PI3K) pathway is one of the most activated pathways in cancer and its activation is central to most deregulated metabolic pathways for supporting the anabolic needs of growing cancer cells. Herein, we provide evidence that thymoquinone inhibits glycolytic metabolism (Warburg effect) in colorectal cancer cell lines. Further, we show that such an abrogation of deranged cell metabolism was due, at least in part, to the inhibition of the rate-limiting glycolytic enzyme, Hexokinase 2 (HK2), via modulating the PI3/AKT axis. While overexpression of HK2 showed that it is essential for fueling glycolytic metabolism as well as sustaining tumorigenicity, its pharmacologic and/or genetic inhibition led to a reduction in the observed effects. The results decipher HK2 mediated inhibitory effects of thymoquinone in modulating its glycolytic metabolism and antitumor effects. In conclusion, we provide evidence of metabolic perturbation by thymoquinone in CRC cells, highlighting its potential to be used/repurposed as an antimetabolite drug, though the latter needs further validation utilizing other suitable cell and/or preclinical animal models.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.