RESUMO
Higher plants continue to afford humankind with many new drugs, for a variety of disease types. In this review, recent phytochemical and biological progress is presented for part of a collaborative multi-institutional project directed towards the discovery of new antitumor agents. The specific focus is on bioactive natural products isolated and characterized structurally from tropical plants collected in Vietnam. The plant collection, identification, and processing steps are described, and the natural products isolated from these species are summarized with their biological activities.
RESUMO
AIMS: The aim of this study was to describe quantitatively the potential demethylating effects of the plant-derived compound isoliquritigenin (ILTG) on the death-associated protein kinase-1 (DAPK1) promoter region of colon cancer and leukemia cell lines. METHODS: Methylation-specific real-time polymerase chain reaction-melting curve analysis (MSP-MCA) was the primary method used. A simple cytotoxicity assay and an ethidium bromide displacement assay were used to evaluate the chemopreventive indices and account for any problems in fluorometric assessment caused by intercalating potential of the compound of interest. RESULTS: ILTG was able to affect the melting curve significantly when using MSP-MCA. ILTG exhibited a demethylating activity on HT-29 colon cancer and HL-60 leukemia cells. CONCLUSION: ILTG found in licorice (Glycyrrhiza glabra) may have the potential for being a cancer chemopreventive agent. From the specific assays performed in this experiment, ILTG appears to possess potential for development as a demethylating agent for either colon cancer or leukemia cancer prevention.
Assuntos
Proteínas Reguladoras de Apoptose/genética , Proteínas Quinases Dependentes de Cálcio-Calmodulina/genética , Chalconas/farmacologia , Neoplasias do Colo/enzimologia , Neoplasias do Colo/genética , Metilação de DNA/efeitos dos fármacos , Leucemia Promielocítica Aguda/enzimologia , Leucemia Promielocítica Aguda/genética , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Proteínas Quinases Associadas com Morte Celular , Inibidores Enzimáticos/farmacologia , Células HL-60 , Células HT29 , Humanos , Regiões Promotoras Genéticas/efeitos dos fármacosRESUMO
Hematologic malignancies account for a substantial percentage of cancers worldwide, and the heterogeneity and biological characteristics of leukemias and lymphomas present unique therapeutic challenges. Although treatment options exist for most of these diseases, many types remain incurable and the emergence of drug resistance is pervasive. Thus, novel treatment approaches are essential to improve outcome. Nearly half of the agents used in cancer therapy today are either natural products or derivatives of natural products. The enormous chemical diversity in nature, coupled with millennia of biological selection, has generated a vast and underexplored reservoir of unique chemical structures with biologic activity. This review will describe the investigation and application of natural products derived from higher plants in the treatment of leukemia and lymphoma and the rationale behind these efforts. In addition to the approved vinca alkaloids and the epipodophyllotoxin derivatives, a number of other plant compounds have shown promise in clinical trials and in preclinical investigations. In particular, we will focus on the discovery and biological evaluation of the plant-derived agent silvestrol, which shows potential for additional development as a new therapeutic agent for B-cell malignancies including chronic lymphocytic leukemia.