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1.
Chem Biodivers ; 16(4): e1900028, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30715794

RESUMO

Di(indol-3-yl)methane (=3,3'-methanediyldi(1H-indole), DIM, 1) is a known weakly antitumoral compound formed by digestion of indole-3-carbinol (=1H-indol-3-ylmethanol), an ingredient of various Brassica vegetables. Out of a series of nine fluoroaryl derivatives of 1, three pentafluorophenyl derivatives 2c, 2h, and 2i were identified that exhibited a two to five times greater anti-proliferative effect and an increased apoptosis induction when compared with 1 in the following carcinoma cell lines: BxPC-3 pancreas, LNCaP prostate, C4-2B prostate, PC3 prostate and the triple-negative MDA-MB-231 breast carcinoma. Compound 2h was particularly efficacious against androgen-refractory C4-2B prostate cancer cells (IC50 =6.4 µm) and 2i against androgen-responsive LNCaP cells (IC50 =6.2 µm). In addition, 2c and 2h exhibited distinct activity in three cancer cell lines resistant to 1.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Produtos Biológicos/farmacologia , Hidrocarbonetos Fluorados/farmacologia , Indóis/farmacologia , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Produtos Biológicos/síntese química , Produtos Biológicos/química , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidrocarbonetos Fluorados/síntese química , Hidrocarbonetos Fluorados/química , Indóis/síntese química , Indóis/química , Simulação de Acoplamento Molecular , Estrutura Molecular , Relação Estrutura-Atividade , Células Tumorais Cultivadas
2.
BMC Cancer ; 18(1): 904, 2018 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-30236079

RESUMO

BACKGROUND: There is an urgent need for more novel and efficacious therapeutic agents and strategies for the treatment of ovarian cancer - one of the most formidable female malignancies. These approaches should be based on comprehensive understanding of the pathobiology of this cancer and focused on decreasing its recurrence and metastasis. The aim of this study was to evaluate the efficacy of five-year maintenance therapy with indole-3-carbinol (I3C) as well as I3C and epigallocatechin-3-gallate (EGCG) conducted before, during, and after combined treatment compared with combined treatment alone in advanced ovarian cancer. METHODS: Patients with stage III-IV serous ovarian cancer were assigned to receive combined treatment plus I3C (arm 1), combined treatment plus I3C and EGCG (arm 2), combined treatment plus I3C and EGCG plus long-term platinum-taxane chemotherapy (arm 3), combined treatment alone without neoadjuvant platinum-taxane chemotherapy (control arm 4), and combined treatment alone (control arm 5). Combined treatment included neoadjuvant platinum-taxane chemotherapy, surgery, and adjuvant platinum-taxane chemotherapy. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and rate of patients with recurrent ovarian cancer with ascites after combined treatment. RESULTS: After five years of follow-up, maintenance therapy dramatically prolonged PFS and OS compared to control. Median OS was 60.0 months (95% CI: 58.0-60.0 months) in arm 1, 60.0 months (95% CI: 60.0-60.0 months) in arms 2 and 3 while 46.0 months (95% СI: 28.0-60.0 months) in arm 4, and 44.0 months (95% СI: 33.0-58.0 months) in arm 5. Median PFS was 39.5 months (95% СI: 28.0-49.0 months) in arm 1, 42.5 months (95% СI: 38.0-49.0 months) in arm 2, 48.5 months (95% СI: 39.0-53.0 months) in arm 3, 24.5 months (95% СI: 14.0-34.0 months) in arm 4, 22.0 months (95% СI: 15.0-26.0 months) in arm 5. The rate of patients with recurrent ovarian cancer with ascites after combined treatment was significantly less in maintenance therapy arms compared to control. CONCLUSIONS: Long-term usage of I3C and EGCG may represent a new promising way of maintenance therapy in advanced ovarian cancer patients, which achieved better treatment outcomes. TRIAL REGISTRATION: Retrospectively registered with ANZCTR number: ACTRN12616000394448 . Date of registration: 24/03/2016.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Terapia Combinada , Feminino , Genes BRCA1 , Humanos , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Modelos de Riscos Proporcionais , Qualidade de Vida , Resultado do Tratamento
3.
Cell Oncol (Dordr) ; 41(4): 463, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30047093

RESUMO

In the title of above mentioned article the word 'versatile' had been replaced by 'multifaceted'.

4.
Cancer Lett ; 423: 153, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29606293

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor in Chief. An investigation by Wayne State University identified a discrepancy between the data reported in Figures 1B, 2B and 3C and the original collected data. The investigation committee concluded that this undermined the scientific basis of the publication, that no credible replacement data were available, and advised that the publication should be retracted.

5.
Cancer Lett ; 423: 154, 2018 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-29606294

RESUMO

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the Editor in Chief. An investigation by Wayne State University identified a discrepancy between the data reported in Figures 5 and the original collected data. The investigation committee concluded that this undermined the scientific basis of the publication, that no credible replacement data were available, and advised that the publication should be retracted.

6.
Cell Oncol (Dordr) ; 41(3): 223-252, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29667069

RESUMO

BACKGROUND: Recent advances in cancer biology have highlighted the relevance of exosomes and nanovesicles as carriers of genetic and biological messages between cancer cells and their immediate and/or distant environments. It has been found that these molecular cues may play significant roles in cancer progression and metastasis. Cancer cells secrete exosomes containing diverse molecules that can be transferred to recipient cells and/or vice versa to induce a plethora of biological processes, including angiogenesis, metastasis formation, therapeutic resistance, epithelial-mesenchymal transition and epigenetic/stemness (re)programming. While exosomes interact with cells within the tumour microenvironment to promote tumour growth, these vesicles can also facilitate the process of distant metastasis by mediating the formation of pre-metastatic niches. Next to their tumour promoting effects, exosomes have been found to serve as potential tools for cancer diagnosis and therapy. The ease of isolating exosomes and their content from different body fluids has led to the identification of diagnostic and prognostic biomarker signatures, as well as to predictive biomarker signatures for therapeutic responses. Exosomes can also be used as cargos to deliver therapeutic anti-cancer drugs, and they can be engineered to serve as vaccines for immunotherapy. Additionally, it has been found that inhibition of exosome secretion, and thus the transfer of oncogenic molecules, holds promise for inhibiting tumour growth. Here we provide recent information on the diverse roles of exosomes in various cellular and systemic processes governing cancer progression, and discuss novel strategies to halt this progression using exosome-based targeted therapies and methods to inhibit exosome secretion and the transfer of pro-tumorigenic molecules. CONCLUSIONS: This review highlights the important role of exosomes in cancer progression and its implications for (non-invasive) diagnostics and the development of novel therapeutic strategies, as well as its current and future applications in clinical trials.


Assuntos
Exossomos/fisiologia , Neoplasias/diagnóstico , Neoplasias/terapia , Envelhecimento , Biomarcadores Tumorais , Comunicação Celular , Transformação Celular Neoplásica , Ensaios Clínicos como Assunto , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Exossomos/metabolismo , Exossomos/ultraestrutura , Humanos , Imunoterapia , Metástase Neoplásica , Neoplasias/tratamento farmacológico , Microambiente Tumoral
7.
Curr Stem Cell Res Ther ; 13(4): 252-264, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29336267

RESUMO

BACKGROUND: Regenerative medicine aims to provide therapeutic treatment for disease or injury, and cell-based therapy is a newer therapeutic approach different from conventional medicine. Ethical issues that rose by the utilisation of human embryonic stem cells (hESC) and the limited capacity of adult stem cells, however, hinder the application of these stem cells in regenerative medicine. Recently, isolation and characterisation of c-kit positive cells from human amniotic fluid, which possess intermediate characteristics between hESCs and adult stem cells, provided a new approach towards realising their promise for fetal and adult regenerative medicine. Despite the number of studies that have been initiated to characterize their molecular signature, research on developing approaches to maintain and enhance their regenerative potential is urgently needed and must be developed. AIM: Thus, this review is focused on understanding their potential uses and factors influencing their pluripotent status in vitro. CONCLUSION: In short, this cell source could be an ideal cellular resource for pluripotent cells for potential applications in allogeneic cellular replacement therapies, fetal tissue engineering, pharmaceutical screening, and in disease modelling.


Assuntos
Líquido Amniótico/citologia , Diferenciação Celular/fisiologia , Terapia Baseada em Transplante de Células e Tecidos , Células-Tronco/citologia , Animais , Humanos , Medicina Regenerativa , Engenharia Tecidual/métodos
9.
Colloids Surf B Biointerfaces ; 157: 490-502, 2017 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-28658642

RESUMO

The current study utilizes folic acid conjugated poly(styrene-co-maleic anhydride) block copolymer (FA-SMA) to enhance the solubility of a hydrophobic but very potent synthetic curcumin-difluorinated (CDF) analog and its targeted delivery to folate receptor-alpha overexpressing cancers. The nanomicelles showed high aqueous solubility. Importantly, the encapsulation of CDF in nanomicelles resulted in high photo-stability of the otherwise photo-labile drug. When the nanomicelles were tested in folate-receptor overexpressing ovarian and cervical cancer cells they exhibited high anticancer activity causing significant cell population to undergo apoptosis due to upregulation of tumor suppressor phosphatase and tensin homolog (PTEN) and inhibition of nuclear factor kappa-B (NFκB), which further confirmed the targeting ability and anticancer potentials of folate-targeted formulations.


Assuntos
Curcumina/química , Ácido Fólico/química , Neoplasias Ovarianas , Polímeros/química , Neoplasias do Colo do Útero , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Feminino , Humanos , Micelas
10.
J Colloid Interface Sci ; 496: 290-299, 2017 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-28236692

RESUMO

Albumin-bound paclitaxel colloidal nanoparticle (Abraxane®) is an FDA approved anticancer formulation available in the market. It is a suspension which is currently used therapeutically for treating cancers of the breast, lung, and pancreas among others. CDF is a novel new and potent synthetic curcumin analogue that is widely used for breast and ovarian cancer. The aim of this study was to use biocompatible albumin as well as folate decorated albumin to formulate colloidal nanoparticles encapsulating curcumin difluorinated (CDF). CDF has demonstrated a 16-fold improvement in stability and remarkable anticancer potency compared to its natural derivative, curcumin. CDF showed marked inhibition of cancer cell growth through down-regulation of multiple miRNAs, up-regulation of phosphatase and tensin homolog (PTEN), and attenuation of histone methyl transferase EZH2. However, CDF is highly hydrophobic and photodegradable with sparing aqueous solubility. In this study, we have formulated albumin nanoparticle using a modified desolvation method, which yielded high CDF loading in a nanoformulation. The physicochemical properties of CDF loaded albumin and folate-decorated albumin nanosuspensions were assessed for particle size, morphology, zeta potential, drug encapsulation efficiency/loading, solubility and drug release. Importantly, the folate ligand decorated albumin nanoparticles were formulated in principle to passively and actively target folate-overexpressing-cancers. In this study, the synthesis and optimization of BSA and folate decorated BSA conjugated CDF nanoparticles are assessed in detail that will be useful for its future clinical translation.


Assuntos
Antineoplásicos/química , Curcumina/análogos & derivados , Curcumina/química , Ácido Fólico/química , Nanopartículas/química , Soroalbumina Bovina/química , Animais , Bovinos , Linhagem Celular Tumoral , Sobrevivência Celular , Química Farmacêutica , Coloides , Portadores de Fármacos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Humanos , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Concentração Osmolar , Tamanho da Partícula , Ligação Proteica , Solubilidade , Propriedades de Superfície
11.
Eur J Med Chem ; 126: 421-431, 2017 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-27912173

RESUMO

Substituted lawsone Mannich bases 2a-e, 3a-e and 4a-e were prepared and tested for their biological activities. The new fatty alkyl substituted compounds 2a-c exhibited strong and selective growth inhibitory activities in the low one-digit micromolar and sub-micromolar range against a panel of human cancer cell lines associated with ROS formation. In addition, compounds 2a-c revealed sub-micromolar anti-trypanosomal activities against parasitic Trypanosoma brucei brucei cells via deformation of the microtubule cytoskeleton. The N-hexadecyl compound 2c was also highly active against locally isolated Entamoeba histolytica parasite samples exceeding the activity of metronidazole.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Bases de Mannich/química , Naftoquinonas/química , Naftoquinonas/farmacologia , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Linhagem Celular Tumoral , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Desenho de Fármacos , Entamoeba histolytica/efeitos dos fármacos , Humanos , Concentração Inibidora 50 , Relação Estrutura-Atividade , Trypanosoma brucei brucei/efeitos dos fármacos
13.
J Colloid Interface Sci ; 484: 33-43, 2016 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-27585998

RESUMO

Conventional chemotherapy using small molecule drugs is marred by several challenges such as short half-life, low therapeutic index and adverse systemic side effects. In this regard, targeted therapies using ligand directed polyamidoamine (PAMAM) dendrimers could be a promising strategy to specifically deliver anticancer drugs to cancer cells overexpressing complementary receptor binding domains. The aim of this study was to utilize folate decorated PAMAM to enhance the aqueous solubility of a highly hydrophobic but very potent anticancer flavonoid analogue, 3,4-difluorobenzylidene diferuloylmethane (CDF) and to deliver it specifically to folate receptor overexpressing cervical cancer cells (HeLa) and ovarian cancer cells (SKOV3). As compared to the non-targeted formulation, the targeted formulation exhibited significant anticancer activity with higher accumulation in folate receptor overexpressing cells, larger population of apoptotic cancer cells, elevated expression of tumor suppressor phosphatase and tensin homolog (PTEN), and inhibition of nuclear factor kappa B (NFκB) which further confirmed the targeting ability and the promising anticancer activity of the folate based nanoformulation.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Curcumina/análogos & derivados , Dendrímeros/química , Portadores de Fármacos/química , Flavonoides/farmacologia , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/química , Curcumina/farmacologia , Diarileptanoides , Flavonoides/química , Receptor 1 de Folato/genética , Receptor 1 de Folato/metabolismo , Ácido Fólico/química , Ácido Fólico/metabolismo , Células HeLa , Humanos , Terapia de Alvo Molecular , NF-kappa B/antagonistas & inibidores , NF-kappa B/genética , NF-kappa B/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Solubilidade
16.
Am J Transl Res ; 8(1): 166-76, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27069550

RESUMO

Consumption of cruciferous vegetables is associated with a decreased risk of developing prostate cancer. Antineoplastic effects of cruciferous vegetables are attributable to bioactive indoles, most prominently, 3, 3'-diindolylmethane (DIM). In addition to effects on proliferation and apoptosis, DIM acts as an antiandrogen in prostate cancer cell lines. This study characterized the effects of prostatic DIM on the androgen receptor (AR) in patients with prostate cancer. Men with localized prostate cancer were treated with a specially formulated DIM capsule designed for enhanced bioavailability (BR-DIM) at a dose of 225 mg orally twice daily for a minimum of 14 days. DIM levels and AR activity were assessed at the time of prostatectomy. Out of 28 evaluable patients, 26 (93%) had detectable prostatic DIM levels, with a mean concentration of 14.2 ng/gm. The mean DIM plasma level on BR-DIM therapy was 9.0 ng/mL; levels were undetectable at baseline and in follow-up samples. AR localization in the prostate was assessed with immunohistochemistry. After BR-DIM therapy, 96% of patients exhibited exclusion of the AR from the cell nucleus. In contrast, in prostate biopsy samples obtained prior to BR-DIM therapy, no patient exhibited AR nuclear exclusion. Declines in PSA were observed in a majority of patients (71%). Compliance was excellent and toxicity was minimal. In summary, BR-DIM treatment resulted in reliable prostatic DIM levels and anti-androgenic biologic effects at well tolerated doses. These results support further investigation of BR-DIM as a chemopreventive and therapeutic agent in prostate cancer.

17.
Int J Biol Sci ; 12(3): 326-37, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26929739

RESUMO

Pancreatic cancer remains the fourth leading cause of cancer-related death in the US and is expected to be the second leading cause of cancer-related death by 2030. Therefore, it is important to better understand the molecular pathogenesis, phenotypes and features of pancreatic cancer in order to design novel molecularly targeted therapies for achieving better therapeutic outcome of patients with pancreatic cancer. Recently, the roles of microRNAs (miRNAs) in the development and progression of pancreatic cancer became a hot topic in the scientific community of pancreatic cancer research. By conducting miRNA expression profiling, the aberrant expression of miRNAs was revealed in the serum and in cancer tissues from patients with pancreatic cancer. These aberrantly expressed miRNAs are critically correlated with the disease stage, drug resistance, and survival of pancreatic cancer patients. Hence, targeting these tiny molecules, the specific miRNAs, could provide an efficient and optimal approach in the therapy of pancreatic cancer. Indeed, the pre-clinical and in vivo experiments showed that nanoparticle delivery of synthetic oligonucleotides or treatment with natural agents could be useful to modulate the expression of miRNAs and thereby inhibit pancreatic cancer growth and progression, suggesting that targeting miRNAs combined with conventional anti-cancer therapeutics could be a novel therapeutic strategy for increasing drug sensitivity and achieving better therapeutic outcome of patients diagnosed with pancreatic cancer.


Assuntos
MicroRNAs/genética , Terapia de Alvo Molecular/métodos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Animais , Humanos , Neoplasias Pancreáticas/tratamento farmacológico
18.
Biometals ; 29(2): 299-310, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26872803

RESUMO

This study was conducted to investigate the mechanism of action involved in the anti-cancer activity of daidzein and identification of cancer specific micro-environment as therapeutic target of this secondary metabolite derived from soy. Our data indicated that daidzein induces cellular DNA breakage, anti-proliferative effects and apoptosis in a concentration-dependent manner. We demonstrated that such a daidzein-induced anti-cancer action involves a copper-dependant pathway in which endogenous copper is mobilized by daidzein and redox-cycled to generate reactive oxygen species which act as an upstream signal leading to pro-oxidant cell death. Further in the context of hypoxia being a resistant factor against standard therapies and that an effect secondary to hypoxia is the intracellular acidification, we show that the anticancer activity of daidzein is modulated positively in acidic pH but copper-specific chelator is still able to inhibit daidzein activity. Moreover, an experimental setup of hypoxia mimic (cobalt chloride) revealed an enhanced sensitivity of cancer cells to the cytotoxic effects of daidzein which was neutralized in the presence of neocuproine. The findings support a paradigm shift from the conventional antioxidant property of dietary isoflavones to molecules capable of initiating a pro-oxidant signaling mediated by reactive oxygen species. Further, the clinical relevance of such an action mechanism in cancer chemoprevention is also proposed. This study identified endogenous copper as a molecular target and acidic pH as a modulating factor for the therapeutic activity of daidzein against cancer. The evidence presented highlights the potential of dietary agents as adjuvants to standard therapeutic regimens.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Cobre/metabolismo , Isoflavonas/farmacologia , Espécies Reativas de Oxigênio/farmacologia , Hipóxia Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Clivagem do DNA , Dano ao DNA , Resistencia a Medicamentos Antineoplásicos , Ensaios de Seleção de Medicamentos Antitumorais , Genoma Humano , Humanos , Concentração de Íons de Hidrogênio , Oxirredução
19.
Mol Nutr Food Res ; 60(6): 1251-63, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26799714

RESUMO

The landscape of cancer has changed considerably in past several years, due mainly to aggressive screening, accumulation of data from basic and epidemiological studies, and the advances in translational research. Natural anticancer agents have always been a part and parcel of cancer research. The initial focus on natural anticancer agents was in context of their cancer chemopreventive properties but their ability to selectively target oncogenic signaling pathways has also been recognized. In light of the rapid advancements in our understanding of the role of microRNAs, cancer stem cells, and epigenetic events in cancer initiation and progression, a number of natural anticancer agents are showing promise in vitro, in vivo as well as in preclinical studies. Moreover, parent structures of natural agents are being extensively modified with the hope of improving efficacy, specificity, and bioavailability. In this article, we focus on two natural agents, 3,3'-diindolylmethane and garcinol, along with 3,4-difluorobenzo curcumin, a synthetic analog of natural agent curcumin. We showcase how these anticancer agents are changing cancer landscape by modulating novel microRNAs, epigenetic factors, and cancer stem cell markers. These activities are relevant and being appreciated for overcoming drug resistance and inhibition of metastases, the two overarching clinical challenges in modern medicine.


Assuntos
Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/prevenção & controle , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Curcumina/análogos & derivados , Curcumina/farmacologia , Suplementos Nutricionais , Epigênese Genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Indóis/farmacologia , MicroRNAs/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Transdução de Sinais , Terpenos/farmacologia
20.
Crit Rev Food Sci Nutr ; 56(9): 1501-18, 2016 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-25365584

RESUMO

Neoplastic conditions associated with gastrointestinal (GI) tract are common worldwide with colorectal cancer alone accounting for the third leading rate of cancer incidence. Other GI malignancies such as esophageal carcinoma have shown an increasing trend in the last few years. The poor survival statistics of these fatal cancer diseases highlight the need for multiple alternative treatment options along with effective prophylactic strategies. Worldwide geographical variation in cancer incidence indicates a correlation between dietary habits and cancer risk. Epidemiological studies have suggested that populations with high intake of certain dietary agents in their regular meals have lower cancer rates. Thus, an impressive embodiment of evidence supports the concept that dietary factors are key modulators of cancer including those of GI origin. Preclinical studies on animal models of carcinogenesis have reflected the pharmacological significance of certain dietary agents called as nutraceuticals in the chemoprevention of GI neoplasia. These include stilbenes (from red grapes and red wine), isoflavones (from soy), carotenoids (from tomatoes), curcuminoids (from spice turmeric), catechins (from green tea), and various other small plant metabolites (from fruits, vegetables, and cereals). Pleiotropic action mechanisms have been reported for these diet-derived chemopreventive agents to retard, block, or reverse carcinogenesis. This review presents a prophylactic approach to primary prevention of GI cancers by highlighting the translational potential of plant-derived nutraceuticals from epidemiological, laboratory, and clinical studies, for the better management of these cancers through consumption of nutraceutical rich diets and their intervention in cancer therapeutics.


Assuntos
Anticarcinógenos , Dieta , Suplementos Nutricionais , Neoplasias Gastrointestinais/prevenção & controle , Animais , Carotenoides , Curcumina , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/epidemiologia , Humanos , Isoflavonas , Estilbenos
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