Abstract
Increasing evidence demonstrates that three classes of molecules originally derived from all-trans-retinoic acid and its synthetic analogues, which function by interacting with the retinoid nuclear receptors, exert their anticancer activities through alternative signaling pathways. Thus, the methylene-linked analogues (4-HBR, 4-HPRCG, and 4-HBRCG) of N-(4-hydroxyphenyl) retinamide (4-HPR) and its O-glucuronide metabolite (4-HPROG), the cinnamic acid analogues (3-Cl-AHPC and AHPC/ST1926) of 6-[3'-(1-adamantyl)-4'-hydroxyphenyl)]-2-naphthalenecarboxylic acid, and N-(2,3-dihydro-2,2,4,4-tetramethyl-6-benzothiopyranyl),N'-(4-nitrophenyl)thiourea (SHetA2) induce cancer cell-cycle arrest and apoptosis mediated most likely through mitochondrial and/or endoplasmic reticulum stress responses. Structure-activity relationships and potential for clinical translation as anticancer therapeutics are presented.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Review
MeSH terms
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Antineoplastic Agents / chemical synthesis
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Antineoplastic Agents / chemistry*
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Antineoplastic Agents / pharmacology
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Apoptosis
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Cinnamates / chemical synthesis
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Cinnamates / chemistry
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Cinnamates / pharmacology
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Fenretinide / analogs & derivatives
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Fenretinide / chemical synthesis
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Fenretinide / chemistry
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Fenretinide / pharmacology
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Glucuronates / chemical synthesis
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Glucuronates / chemistry
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Glucuronates / pharmacology
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Receptors, Retinoic Acid / chemistry
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Receptors, Retinoic Acid / metabolism*
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Retinoids / chemical synthesis
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Retinoids / chemistry*
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Retinoids / pharmacology
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Structure-Activity Relationship
Substances
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Antineoplastic Agents
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Cinnamates
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Glucuronates
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N-((4-hydroxyphenyl)retinamide)-O-glucuronide
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Receptors, Retinoic Acid
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Retinoids
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cinnamic acid
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Fenretinide