ArticleDigestive diseases and sciences2015
Thymoquinone Pretreatment Overcomes the Insensitivity and Potentiates the Antitumor Effect of Gemcitabine Through Abrogation of Notch1, PI3K/Akt/mTOR Regulated Signaling Pathways in Pancreatic Cancer.
Article in Digestive diseases and sciences, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 90 citations in OpenAlex.
- Herbals and Plants in the Treatment of Pancreatic Cancer: A Systematic Review of Experimental and Clinical Studies.Nutrients · 2022Pooled it
- Thymoquinone Potentiates Docetaxel-Induced Antitumor Activity with the Involvement of ROS and PI3K/AKT Pathway Modulation in Triple-Negative Breast Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Targeting Cancer Through Thymoquinone: From Molecular Mechanisms to Clinical Prospects.International journal of molecular sciences · 2025Review
- Potential role of thymoquinone to treat gastrointestinal cancers: insights into its molecular mechanisms.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Unlocking the Potential of Bioactive Compounds in Pancreatic Cancer Therapy: A Promising Frontier.Biomolecules · 2025Review
- Chemopreventive Agents from Nature: A Review of Apigenin, Rosmarinic Acid, and Thymoquinone.Current issues in molecular biology · 2024Review
- Tumoricidal properties of thymoquinone on human colorectal adenocarcinoma cells via the modulation of autophagy.BMC complementary medicine and therapies · 2024Article
- Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer.Cancer cell international · 2023Review
- Effect ofCurrent issues in molecular biology · 2023Review
- Thymoquinone affects the gemcitabine sensitivity of pancreatic cancer by regulating collagen via hypoxia inducible factor-1α.Frontiers in pharmacology · 2023Article
- Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis.Experimental and therapeutic medicine · 2022Article
- The effects of thymoquinone on pancreatic cancer and immune cells.Revista da Associacao Medica Brasileira (1992) · 2022Article
- Anticancer and Anti-Metastatic Role of Thymoquinone: Regulation of Oncogenic Signaling Cascades by Thymoquinone.International journal of molecular sciences · 2022Review
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Potential anticancer properties and mechanisms of thymoquinone in osteosarcoma and bone metastasis.Cellular & molecular biology letters · 2022Review
- PI3K-AKT Pathway Modulation by Thymoquinone Limits Tumor Growth and Glycolytic Metabolism in Colorectal Cancer.International journal of molecular sciences · 2022Article
- Drug-Herb Interactions among Thai Herbs and Anticancer Drugs: A Scoping Review.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Advances in research on the relationship between thymoquinone and pancreatic cancer.Frontiers in oncology · 2022Review
- Metformin and Thymoquinone Synergistically Inhibit Proliferation of Imatinib-Resistant Human Leukemic Cells.Frontiers in pharmacology · 2022Article
- Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe gemcitabine-insensitivity remains the main challenge for pancreatic cancer treatment. Thymoquinone, the predominant bioactive ingredient of Nigella sativa, has been shown to possess promising anti-cancer and chemo-sensitizing effects on pancreatic cancer, however, its meticulous mechanism is still indistinct.
aimThe objective of the present study was to investigate the potency of thymoquinone in combination with gemcitabine in inducing apoptosis and preventing the development of gemcitabine-insensitivity in pancreatic cancer cells.
methodsThe anti-tumor effects of thymoquinone and gemcitabine were analyzed via evaluation of alterations of cell viability, tumor weight, apoptosis-related proteins, caspase-3, -9 activities and NF-κB DNA binding activity in pancreatic cancer cells in vitro and PANC-1 cells orthotopic xenograft in vivo.
resultsThymoquinone pretreatment following gemcitabine treatment synergistically caused an increase in pancreatic cancer cells apoptosis and tumor growth inhibition both in vitro and in vivo. The novel combinational regimen also contributes to alterations of multiple molecular signaling targets, such as the suppression of Notch1, NICD accompanying with up-regulation of PTEN, the inactivation of Akt/mTOR/S6 signaling pathways, and the suppression of phosphorylation and nuclear translocation of p65 induced by TNF-α. Thymoquinone pretreatment and gemcitabine also induced down-regulation of anti-apoptotic Bcl-2, Bcl-xL, XIAP and up-regulation and activation of pro-apoptotic molecules including Caspase-3, Caspase-9, Bax and increased release of cytochrome c.
conclusionsThis novel modality of thymoquinone pretreatment can enhance the anti-cancer activity of gemcitabine and may be a promising option in the treatment of pancreatic cancer.
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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.