title: Targeting death receptors for TRAIL by agents designed by Mother Nature.
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.
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Sahdeo
authors.initials: S
authors.lastname: Prasad
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Ji Hye
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Subash C
authors.initials: SC
authors.lastname: Gupta
authors.affiliation: Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: aggarwal@mdanderson.org.
authors.forename: Bharat B
authors.initials: BB
authors.lastname: Aggarwal
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019587:Dietary Supplements; D004357:Drug Synergism; D006801:Humans; D053218:Receptors, Death Domain / Q000819:agonists / Q000276:immunology / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D053218:Receptors, Death Domain; D053221:TNF-Related Apoptosis-Inducing Ligand
keywords: ROS; TRAIL; apoptosis; cancer; death receptor; natural products; nutraceuticals