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Updated: Apr 25, 2026
MEDUSA for Identifying Death Regulatory Genes in Chemo-genetic Profiling Data
Published on: February 7, 2025
Targeting death receptors for TRAIL by agents designed by Mother Nature
Sahdeo Prasad1, Ji Hye Kim1, Subash C Gupta1
1Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
Abstract:
Selective killing of cancer cells is one of the major goals of cancer therapy. Although chemotherapeutic agents are being used for cancer treatment, they lack selectivity toward tumor cells. Among the six different death receptors (DRs) identified to date, DR4 and DR5 are selectively expressed on cancer cells. Therefore, unlike chemotherapeutic agents, these receptors can potentially mediate selective killing of tumor cells. In this review we outline various nutraceuticals derived from 'Mother Nature' that can upregulate DRs and thus potentiate apoptosis. These nutraceuticals increase tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis of cancer cells through different mechanisms. First, nutraceuticals have been found to induce DRs through the upregulation of various signaling molecules. Second, nutraceuticals can downregulate tumor cell-survival pathways. Third, nutraceuticals alone have been found to activate cell-death pathways. Although both TRAIL and agonistic antibodies against DR4 and DR5 are in clinical trials, combination with nutraceuticals is likely to boost their anticancer potential.
Insights
Certain natural compounds, or nutraceuticals, can enhance cancer therapy by upregulating death receptors (DRs). This boosts the cancer-killing effects of TRAIL-based treatments, offering a promising approach for selective tumor cell apoptosis.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Selective cancer cell killing is a key goal in cancer therapy.
- Conventional chemotherapeutics lack tumor cell selectivity.
- Death Receptors 4 (DR4) and 5 (DR5) are selectively expressed on cancer cells, offering therapeutic targets.
Purpose of the Study:
- To review nutraceuticals that upregulate DR4 and DR5.
- To explore how nutraceuticals potentiate tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)-induced apoptosis.
- To highlight the potential of combining nutraceuticals with DR4/DR5-targeted therapies.
Main Methods:
- Literature review of studies on nutraceuticals and cancer cell death pathways.
- Analysis of mechanisms by which nutraceuticals modulate DR expression and signaling.
- Examination of evidence for nutraceuticals' effects on TRAIL-induced apoptosis.
Main Results:
- Nutraceuticals upregulate DR4 and DR5 expression through various signaling molecules.
- Certain nutraceuticals downregulate tumor cell-survival pathways.
- Some nutraceuticals can independently activate cancer cell-death pathways.
Conclusions:
- Nutraceuticals can enhance the efficacy of TRAIL and DR4/DR5 agonistic antibodies.
- Combining nutraceuticals with targeted therapies offers a strategy to boost anticancer potential.
- Natural compounds represent a promising avenue for improving selective cancer treatment.
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