Effects of medicinal plants and natural compounds in models of prostate cancer related to sex steroids: A systematic review.

Prostate cancer remains a health problem for men. Targeting androgen (AR) and estrogen (ER) receptors improves the outcomes of the disease, and many medicinal plants exert their effects by modulating these pathways. Therefore, a systematic review was conducted to identify medicinal plants and their natural compounds that may modulate the AR and/or ER pathways in cell and animal models. A search was conducted across EMBASE, LILACS, PubMed, Scopus, and Web of Science, with grey literature from Google SCHOLAR and ProQuest. Two authors independently selected eligible studies based on their titles and abstracts, and a third author resolved conflicts. Then, data from the full text of eligible studies were extracted and synthesized. In total, 75 studies were included. Results showed the effects of several different medicinal plants and natural compounds in reduction of AR and/or ER transcription and translation and AR secondary effects: cell growth reduction, induction of apoptosis, and cell cycle arrest. In animal models, tumor size reduction, increase in apoptosis, and downregulation of AR expression in tumors were also observed. No single phytochemical group concentrating molecules with anti-AR and/or ER activity was identified. Nevertheless, several phytochemical compounds showed potential for future clinical studies in the management of the disease.

Decaffeinated coffee improves insulin sensitivity in healthy men.

Epidemiological studies have found coffee consumption is associated with a lower risk for type 2 diabetes mellitus, but the underlying mechanisms remain unclear. Thus, the aim of this randomised, cross-over single-blind study was to investigate the effects of regular coffee, regular coffee with sugar and decaffeinated coffee consumption on glucose metabolism and incretin hormones. Seventeen healthy men participated in five trials each, during which they consumed coffee (decaffeinated, regular (containing caffeine) or regular with sugar) or water (with or without sugar). After 1 h of each intervention, they received an oral glucose tolerance test with one intravenous dose of [1-13C]glucose. The Oral Dose Intravenous Label Experiment was applied and glucose and insulin levels were interpreted using a stable isotope two-compartment minimal model. A mixed-model procedure (PROC MIXED), with subject as random effect and time as repeated measure, was used to compare the effects of the beverages on glucose metabolism and incretin parameters (glucose-dependent insulinotropic peptide (GIP)) and glucagon-like peptide-1 (GLP-1)). Insulin sensitivity was higher with decaffeinated coffee than with water (P<0·05). Regular coffee with sugar did not significantly affect glucose, insulin, C-peptide and incretin hormones, compared with water with sugar. Glucose, insulin, C-peptide, GLP-1 and GIP levels were not statistically different after regular and decaffeinated coffee compared with water. Our findings demonstrated that the consumption of decaffeinated coffee improves insulin sensitivity without changing incretin hormones levels. There was no short-term adverse effect on glucose homoeostasis, after an oral glucose challenge, attributable to the consumption of regular coffee with sugar.

Cytotoxic Effect of Erythroxylum suberosum Combined with Radiotherapy in Head and Neck Cancer Cell Lines.

The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

Cytotoxic effect of Erythroxylum daphnites extract is associated with G1 cell cycle arrest and apoptosis in oral squamous cell carcinoma.

Plant-derived molecules showing antineoplastic effects have recently gained increased attention as potential adjuvants to traditional therapies for various cancers. Cerrado biome in Brazil contains high floral biodiversity, but knowledge about the potential therapeutic effects of compounds derived from that flora is still limited. The present study investigated the antineoplastic activity of Erythroxylum daphnites Mart., a Brazilian native plant from Cerrado biome, in the SCC-9 oral squamous cell carcinoma cell line. Cells were treated with various concentrations of hexane extract of Erythroxylum daphnites leaves (EDH) and assessed for cytotoxicity, proliferation, and apoptosis. Thin layer chromatography was conducted to characterize the substances present in EDH. Our results showed that EDH exerted anti-proliferative effects in SCC-9 cells by stabilizing the cell cycle at G1 phase in association with reduced intracellular levels of cyclins D and E and increased level of p21. EDH also demonstrated pro-apoptotic properties, as shown by an increased expression of caspase-3. Triterpenes were the major constituents of EDH. Our findings demonstrated a cytotoxic effect of EDH against SCC-9 cells in vitro mediated by the restraint of cellular proliferation and induction of apoptosis. Taken together, these findings support EDH constituents as potential therapeutic adjuvants for oral cancer.

Cytotoxic Effect of Erythroxylum suberosum Combined with Radiotherapy in Head and Neck Cancer Cell Lines

Abstract The mouth and oropharynx cancer is the 6th most common type of cancer in the world. The treatment may involve surgery, chemotherapy and radiotherapy. More than 50% of drugs against cancer were isolated from natural sources, such as Catharanthus roseus and epipodophyllotoxin, isolated from Podophyllum. The biggest challenge is to maximize the control of the disease, while minimizing morbidity and toxicity to the surrounding normal tissues. The Erythroxylum suberosum is a common plant in the Brazilian Cerrado biome and is popularly known as "cabelo-de-negro". The objective of this study was to evaluate the cytotoxic activity of Erythroxylum suberosum plant extracts of the Brazilian Cerrado biome associated with radiotherapy in human cell lines of oral and hypopharynx carcinomas. Cells were treated with aqueous, ethanolic and hexanic extracts of Erythroxylum suberosum and irradiated at 4 Gy, 6 Gy and 8 Gy. Cytotoxicity was evaluated by MTT assay and the absorbance was measured at 570 nm in a Beckman Counter reader. Cisplatin, standard chemotherapy, was used as positive control. The use of Erythroxylum suberosum extracts showed a possible radiosensitizing effect in vitro for head and neck cancer. The cytotoxicity effect in the cell lines was not selective and it is very similar to the effect of standard chemotherapy. The aqueous extract of Erythroxylum suberosum, combined with radiotherapy was the most cytotoxic extract to oral and hypopharynx carcinomas.

Resumo O câncer de boca e de orofaringe emerge como o 6º tipo de câncer mais comum no mundo. O tratamento pode envolver cirurgia, quimioterapia e radioterapia. Mais de 50% das drogas com atividade de combate ao câncer foram isoladas de fontes naturais, tais como a Catharanthus roseus e a epipodofilotoxina, isolada de Podophyllum. O maior desafio é maximizar o controle da doença, enquanto minimiza a morbidade e toxicidade para os tecidos normais circundantes. O Erythroxylum suberosum é uma planta comum no bioma Cerrado brasileiro e é popularmente conhecida como "cabelo-de-negro". O objetivo deste estudo foi avaliar a citotoxicidade dos extratos da planta Erythroxylum suberosum do bioma Cerrado brasileiro, associados à radioterapia em linhagens celulares humanas de carcinomas de língua e de hipofaringe. As células foram tratadas com os extratos aquoso, etanólico e hexânico do Erythroxylum suberosum e irradiadas com 4 Gy, 6 Gy e 8 Gy. A citotoxidade foi avaliada pelo ensaio de MTT e a absorvância foi medida a 570 nm em uma leitora Beckman. A cisplatina, quimioterápico padrão, foi utilizada como controle positivo. O uso de extratos de Erythroxylum suberosum mostrou potencial efeito radiosensibilizante in vitro no câncer de cabeça e pescoço. O efeito da citotoxicidade nas linhagens foi de forma não seletiva e muito semelhante ao efeito da quimioterapia padrão. O extrato aquoso de Erythroxylum suberosum, combinado com radioterapia, foi o extrato mais citotóxico para os carcinomas de língua e hipofaringe, associados à radioterapia.

Radiation induced a supra-additive cytotoxic effect in head and neck carcinoma cell lines when combined with plant extracts from Brazilian Cerrado biome.

OBJECTIVES: Antineoplastic effects of molecules derived from plants have recently gained increasing attention as an additive to traditional therapies. The aim of this study was to evaluate the cytotoxic activity of plant extracts from the Brazilian Cerrado biome associated with radiotherapy in head and neck carcinoma cells (HNSCC). MATERIALS AND METHODS: Fifteen extracts derived from five Cerrado plants were tested in HNSCC cell lines (SCC-25, SCC-9, FaDu) and keratinocyte cells (HaCat). Cell cytotoxicity of extracts and association extract/radiation (2Gy/min) was assessed by MTT assay. Cisplatin (50 µg/mL) was used as a positive control. Extracts with the major cytotoxic activity were selected and their IC50 concentrations were defined. Apoptosis was assessed using flow cytometric analysis. RESULTS: Ten isolated extracts resulted in moderate cytotoxicity (>20 and ≤ 50 % of viable cells), while three extracts induced severe cytotoxic effects (≤ 20 % of viable cells). Plant extracts treatment improved radiotherapy cytotoxicity in all cell lines. Although plant extracts are not as potent as cisplatin plus radiation, in FaDu cells, seven extracts associated with irradiation showed cytotoxic activity similar or better than the association of cisplatin and radiation. Hexanic extract of Erythroxylum daphinites could induce apoptosis in oral cancer cells; however, necrosis was the prevalent kind of death in FaDu cells treated with hexanic extract of Erythroxylum suberosum. CONCLUSIONS: Pre-treatment of HNSCC cells with the extract derived from Cerrado plants followed by irradiation induced a supra-additive cytotoxic effect. CLINICAL RELEVANCE: This study highlights the potential biological relevance of the Cerrado biome when associated with traditional therapy for cancer.