3,3′-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways

Reyes-Hernández O.D. Figueroa-González G. Quintas-Granados L.I. Gutiérrez-Ruíz S.C. Hernández-Parra H. Romero-Montero A. Del Prado-Audelo M.L. Bernal-Chavez S.A. Cortés H. Peña-Corona S.I. Kiyekbayeva L. Ateşşahin D.A. Goloshvili T. Leyva-Gómez G. Sharifi-Rad J.
December 2023 BioMed Central Ltd

Cancer Cell International
2023 #23 Issue 1

Dietary compounds in cancer prevention have gained significant consideration as a viable method. Indole-3-carbinol (I3C) and 3,3′-diindolylmethane (DIM) are heterocyclic and bioactive chemicals found in cruciferous vegetables like broccoli, cauliflower, cabbage, and brussels sprouts. They are synthesized after glycolysis from the glucosinolate structure. Clinical and preclinical trials have evaluated the pharmacokinetic/pharmacodynamic, effectiveness, antioxidant, cancer-preventing (cervical dysplasia, prostate cancer, breast cancer), and anti-tumor activities of I3C and DIM involved with polyphenolic derivatives created in the digestion showing promising results. However, the exact mechanism by which they exert anti-cancer and apoptosis-inducing properties has yet to be entirely understood. Via this study, we update the existing knowledge of the state of anti-cancer investigation concerning I3C and DIM chemicals. We have also summarized; (i) the recent advancements in the use of I3C/DIM as therapeutic molecules since they represent potentially appealing anti-cancer agents, (ii) the available literature on the I3C and DIM characterization, and the challenges related to pharmacologic properties such as low solubility, and poor bioavailability, (iii) the synthesis and semi-synthetic derivatives, (iv) the mechanism of anti-tumor action in vitro/in vivo, (v) the action in cellular signaling pathways related to the regulation of apoptosis and anoikis as well as the cell cycle progression and cell proliferation such as peroxisome proliferator-activated receptor and PPARγ agonists; SR13668, Akt inhibitor, cyclins regulation, ER-dependent-independent pathways, and their current medical applications, to recognize research opportunities to potentially use these compounds instead chemotherapeutic synthetic drugs.

3,3-diindolylmethane (DIM) , Anti-tumor action , Cancer , Chemotherapeutic drugs , Indole-3-carbinol (I3C)

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Laboratorio de Biología Molecular del Cáncer, Facultad de Estudios Superiores Zaragoza, UMIEZ, Universidad Nacional Autónoma de México, Ciudad de México, 09230, Mexico
Laboratorio de Farmacogenética, Facultad de Estudios Superiores Zaragoza, UMIEZ, Universidad Nacional Autónoma de México, Ciudad de México, 09230, Mexico
Universidad Mexiquense del Bicentenario, Unidad de Estudios Superiores Tultitlán, Mexico, Mexico
Departamento de Farmacia, Facultad de Química, Universidad Nacional Autónoma de México, Ciudad de México, 04510, Mexico
Escuela de Ingeniería y Ciencias, Tecnologico de Monterrey, Campus Ciudad de México, C. Puente 222, Ciudad de México, 14380, Mexico
Laboratorio de Medicina Genómica, Departamento de Genómica, Instituto Nacional de Rehabilitación Luis Guillermo Ibarra Ibarra, Ciudad de Mexico, Mexico
Pharmaceutical School, Department of Pharmaceutical Technology, Asfendiyarov Kazakh National Medical University, Almaty, Kazakhstan
Faculties of Pharmacy, Public Health and Nursing, Kazakh-Russian Medical University, Almaty, Kazakhstan
Baskil Vocational School, Department of Plant and Animal Production, Fırat University, Elazıg, 23100, Turkey
Department of Plant Physiology and Genetic Resources, Institute of Botany, Ilia State University, Tbilisi, 0162, Georgia
Facultad de Medicina, Universidad del Azuay, Cuenca, Ecuador

Laboratorio de Biología Molecular del Cáncer
Laboratorio de Farmacogenética
Universidad Mexiquense del Bicentenario
Departamento de Farmacia
Escuela de Ingeniería y Ciencias
Laboratorio de Medicina Genómica
Pharmaceutical School
Faculties of Pharmacy
Baskil Vocational School
Department of Plant Physiology and Genetic Resources
Facultad de Medicina

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