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1.
Nutrients ; 16(18)2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39339648

RESUMO

Colorectal cancer (CRC) is one of the top 10 most common cancers worldwide and caused approximately 10 million deaths in 2022. CRC mortality has increased by 10% since 2020 and 52.000 deaths will occur in 2024, highlighting the limitations of current treatments due to ineffectiveness, toxicity, or non-adherence. The widely used chemotherapeutic agent, 5-fluorouracil (5-FU), is associated with several adverse effects, including renal, cardiac, and hepatic toxicity; mucositis; and resistance. Taurine (TAU), an essential ß-amino acid with potent antioxidant, antimutagenic, and anti-inflammatory properties, has demonstrated protective effects against tissue toxicity from chemotherapeutic agents like doxorubicin and cisplatin. Taurine deficiency is linked to aging and cancers such as breast and colon cancer. This study hypothesized that TAU may mitigate the adverse effects of 5-fluorouracil (5-FU). Carcinogenesis was chemically induced in rats using 1,2-dimethylhydrazine (DMH). Following five months of cancer progression, taurine (100 mg/kg) was administered orally for 8 days, and colon tissues were analyzed. The results showed 80% of adenocarcinoma (AC) in DMH-induced control animals. Notably, the efficacy of 5-FU showed 70% AC and TAU 50% while, in the 5-FU + TAU group, no adenocarcinoma was observed. No differences were observed in the inflammatory infiltrate or the expression of genes such as K-ras, p53, and Ki-67 among the cancer-induced groups whereas APC/ß-catenin expression was increased in the 5FU + TAU-treated group. The mitotic index and dysplasia were increased in the induced 5-FU group and when associated with TAU, the levels returned to normal. These data suggest that 5-FU exhibits a synergic anticancer effect when combined with taurine.


Assuntos
Neoplasias do Colo , Sinergismo Farmacológico , Fluoruracila , Taurina , Taurina/farmacologia , Animais , Fluoruracila/farmacologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/metabolismo , Ratos , Masculino , Modelos Animais de Doenças , Adenocarcinoma/tratamento farmacológico , 1,2-Dimetilidrazina , Ratos Wistar , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia
2.
Nutrients ; 8(11)2016 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-27834913

RESUMO

Resveratrol and curcumin are natural products with important therapeutic properties useful to treat several human diseases, including cancer. In the last years, the number of studies describing the effect of both polyphenols against cancer has increased; however, the mechanism of action in all of those cases is not completely comprehended. The unspecific effect and the ability to interfere in assays by both polyphenols make this challenge even more difficult. Herein, we analyzed the anticancer activity of resveratrol and curcumin reported in the literature in the last 11 years, in order to unravel the molecular mechanism of action of both compounds. Molecular targets and cellular pathways will be described. Furthermore, we also discussed the ability of these natural products act as chemopreventive and its use in association with other anticancer drugs.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Curcumina/farmacologia , Neoplasias/tratamento farmacológico , Estilbenos/farmacologia , Animais , Humanos , Resveratrol
3.
Molecules ; 21(1): 42, 2015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26729077

RESUMO

Prodrug design is a widely known molecular modification strategy that aims to optimize the physicochemical and pharmacological properties of drugs to improve their solubility and pharmacokinetic features and decrease their toxicity. A lack of solubility is one of the main obstacles to drug development. This review aims to describe recent advances in the improvement of solubility via the prodrug approach. The main chemical carriers and examples of successful strategies will be discussed, highlighting the advances of this field in the last ten years.


Assuntos
Pró-Fármacos/síntese química , Pró-Fármacos/farmacologia , Disponibilidade Biológica , Sistemas de Liberação de Medicamentos , Desenho de Fármacos , Pró-Fármacos/química , Solubilidade
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