ArticleBiochemical pharmacology2013
Tamoxifen magnifies therapeutic impact of ceramide in human colorectal cancer cells independent of p53.
Article in Biochemical pharmacology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
20 citing papers in PubMed, 43 citations in OpenAlex.
- IONIC NANOMEDICINE STRATEGY TO DEVELOP EFFECTIVE CHEMO-PTT COMBINATION CANCER THERAPEUTICS.World journal of pharmaceutical science and research · 2024Article
- The Drug Transporter P-Glycoprotein and Its Impact on Ceramide Metabolism-An Unconventional Ally in Cancer Treatment.International journal of molecular sciences · 2024Review
- Tamoxifen Twists Again: On and Off-Targets in Macrophages and Infections.Frontiers in pharmacology · 2022Review
- Dietary Sphingolipids Contribute to Health via Intestinal Maintenance.International journal of molecular sciences · 2021Review
- Targeting Sphingolipids for Cancer Therapy.Frontiers in oncology · 2021Review
- Alterations of Lipid Metabolism in Cancer: Implications in Prognosis and Treatment.Frontiers in oncology · 2020Review
- Pivotal role of mitophagy in response of acute myelogenous leukemia to a ceramide-tamoxifen-containing drug regimen.Experimental cell research · 2019Article
- FTY720 enhances the anti-tumor activity of carboplatin and tamoxifen in a patient-derived xenograft model of ovarian cancer.Cancer letters · 2018Article
- Sphingolipid metabolism and drug resistance in ovarian cancer.Cancer drug resistance (Alhambra, Calif.) · 2018Article
- Review
- Role of P-glycoprotein inhibitors in ceramide-based therapeutics for treatment of cancer.Biochemical pharmacology · 2017Article
- Zoledronic Acid Regulates Autophagy and Induces Apoptosis in Colon Cancer Cell Line CT26.BioMed research international · 2017Article
- Ceramide-tamoxifen regimen targets bioenergetic elements in acute myelogenous leukemia.Journal of lipid research · 2016Article
- Lipidome in colorectal cancer.Oncotarget · 2016Review
- Tamoxifen induces a pluripotency signature in breast cancer cells and human tumors.Molecular oncology · 2015Article
- Tamoxifen regulation of sphingolipid metabolism--Therapeutic implications.Biochimica et biophysica acta · 2015Review
- Engraftment of Human Primary Acute Myeloid Leukemia Defined by Integrated Genetic Profiling in NOD/SCID/IL2rγnull Mice for Preclinical Ceramide-Based Therapeutic Evaluation.Journal of leukemia (Los Angeles, Calif.) · 2014Article
- Sphingolipids in colon cancer.Biochimica et biophysica acta · 2014Review
- Bcl2L13 is a ceramide synthase inhibitor in glioblastoma.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Nanodrug delivery in reversing multidrug resistance in cancer cells.Frontiers in pharmacology · 2014Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Poor prognosis in patients with later stage colorectal cancer (CRC) necessitates the search for new treatment strategies. Ceramide, because of its role in orchestrating death cascades in cancer cells, is a versatile alternative. Ceramide can be generated by exposure to chemotherapy or ionizing radiation, or it can be administered in the form of short-chain analogs (C6-ceramide). Because intracellular P-glycoprotein (P-gp) plays a role in catalyzing the conversion of ceramide to higher sphingolipids, we hypothesized that administration of P-gp antagonists with C6-ceramide would magnify cell death cascades. Human CRC cell lines were employed, HCT-15, HT-29, and LoVo. The addition of either tamoxifen, VX-710, verapamil, or cyclosporin A, antagonists of P-gp, enhanced C6-ceramide cytotoxicity in all cell lines. In depth studies with C6-ceramide and tamoxifen in LoVo cells showed the regimen induced PARP cleavage, caspase-dependent apoptosis, mitochondrial membrane permeabilization (MMP), and cell cycle arrest at G1 and G2. At the molecular level, the regimen, but not single agents, induced time-dependent upregulation of tumor suppressor protein p53; however, introduction of a p53 inhibitor staved neither MMP nor apoptosis. Nanoliposomal formulations of C6-ceramide and tamoxifen were also effective, yielding synergistic cell kill. We conclude that tamoxifen is a favorable adjuvant for enhancing C6-ceramide cytotoxicity in CRC, and demonstrates uniquely integrated effects. The high frequency of expression of P-gp in CRC presents an adventitious target for complementing ceramide-based therapies, a strategy that could hold promise for treatment of resistant disease.
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