Reduction of oxidative stress and ornithine decarboxylase expression in a human prostate cancer cell line PC-3 by a combined treatment with α-tocopherol and naringenin.

Differentiation of a human aggressive PC-3 cancer cell line was obtained, in a previous investigation, by the synergic effect of α-tocopherol (α-TOC) and naringenin (NG). This combined treatment induced apoptosis and subsequent reduction of the PC-3 cell proliferation and invasion, by a pro-differentiating action. Since one of the peculiar characteristics of NG and α-TOC is their strong antioxidant activity, this study aimed to investigate their potential effect on the activity of the main enzymes involved in the antioxidant mechanism in prostate cancer cells. NG and α-TOC administered singularly or combined in the PC-3 cell line, affected the activity of several enzymes biomarkers of the cellular antioxidant activity, as well as the concentration of total glutathione (GSH + GSSG) and thiobarbituric acid reactive substances (TBARS). The combined treatment increased the TBARS levels and superoxide dismutase (SOD) activity, while decreased the glutathione S-transferase (GST), glutathione reductase (GR), and glyoxalase I (GI) activities. The results obtained indicate that a combined treatment with these natural compounds mitigated the oxidative stress in the human PC-3 cell line. In addition, a significant reduction of both ornithine decarboxylase (ODC) expression and intracellular levels of polyamines, both well-known positive regulators of cell proliferation, accompanied the reduction of oxidative stress observed in the combined α-TOC and NG treatment. Considering the established role of polyamines in cell differentiation, the synergism with NG makes α-TOC a potential drug for further study on the differentiation therapy in prostate cancer patients.

Oral nutritional supplement prevents weight loss and reduces side effects in patients in advanced lung cancer chemotherapy.

Weight loss in patients with cancer is caused by cancer cachexia and chemotherapy-induced nausea and vomiting. Recent developments in antiemetic drugs have substantially improved nausea and vomiting, but this intervention did not reduce weight loss and other more severe side effects of chemotherapy, like anorexia, weakness, cough, dyspnea, hemoptysis, and pain. This study aimed to investigate the effects of nutrition intervention with a food supplement, during chemotherapy in patients with advanced nonsquamous non-small cell lung cancer (NSCLC). Patients received individualized nutrition counseling by a registered dietitian and were provided with oral supplements of Texidrofolico® for 90 days. Bodyweight and the mentioned other side effects were evaluated at baseline and after 90 days of intervention. To assess the effects of this dietary supplement, a total of 30 patients were retrospectively enrolled as controls, and the bodyweight and change in side effects of chemotherapy were compared with those observed in 30 Texidrofolico®-treated patients. After 90-day intervention, by oral supplement of Texidrofolico®, the patients, during the course of cytotoxic chemotherapy, showed an improved quality of life and not significant weight and BMI loss respect the control group. Furthermore, the number of patients, treated with Texidrofolico® who maintained or increased their body weight, after 90 days of treatment was significantly higher than in the control group. The effects of treatment with the food supplement have also been studied from a metabolic point of view. It was possible to find that one of the known markers of tumor growth, plasma polyamines, was reduced after the treatment. A possible relationship between these biogenic amines and the folate cycle is discussed. In conclusion, early intensive nutrition intervention with oral supplements of Texidrofolico® during chemotherapy of NSCLC patients prevents weight loss and it is beneficial for their quality of life.

Selected terpenes from leaves of Ocimum basilicum L. induce hemoglobin accumulation in human K562 cells.

Re-expression of fetal hemoglobin (HbF) was proposed as a possible therapeutic strategy for ß-haemoglobinopathies. Although several inducers of HbF were tested in clinical trials, only hydroxyurea (HU) received FDA approval. Despite it produced adequate HbF levels only in half of HU-treated SCD patients, and was ineffective at all in ß-thalassemia patients, beneficial effects of this approach suggested to continue in this direction identifying further molecules capable of inducing HbF. We tested the potential of essential oil isolated from Ocimum basilicum L. leaves (ObEO) in inducing hemoglobin biosynthesis. Initially, dose-dependent effect and kinetics of hemoglobin accumulation in K562 cells after treatment with ObEO were evaluated. ObEO induced dose-dependent hemoglobin accumulation superior to hydroxyurea and rapamycin and a strongest γ-globin mRNA expression. Terpenes composition of ObEO was studied by GC-MS. Three main constituents, linalool, eugenol and eucalyptol, represented about 75% of total. A blend of these three terpenes fully replicated the ObEO's biological effect, thus indicating that one of them or all together could be the active ingredients. When terpenes were tested individually, eugenol was the only one inducing stable hemoglobin accumulation, while eucalyptol and linalool produced only a small transient response. However, eugenol potential was strongly enhanced in the presence of eucalyptol and linalool, suggesting a synergistic effect on hemoglobin accumulation. By these results, the discovery of a new inducer and the interesting activity of a blend of major terpenes from ObOE on Hb accumulation could have positive fallouts on ß-thalassemia and sickle cells anemia.

Periprostatic Perineurioma, Description of a Case With Unusual Localization.

Perineurioma is a rare entity, it is a benign peripheral nerve sheath tumor entirely composed of perineurial cells. A 62-year-old male patient was admitted to our hospital, suffering from scrotal and pelvic pain combined with a severe and continuous pain in his right thigh. A transrectal ultrasound revealed a periprostatic oval lesion of about 5 cm in maximum diameter. A sovrapubic laparotomy was performed with a complete tumor excision. The morphological and immunohistochemical data were most consistent with the diagnosis of perineurioma.

Synergic effect of α-tocopherol and naringenin in transglutaminase-induced differentiation of human prostate cancer cells.

Prostate cancer is the second most common cancer in men worldwide. Its prevention and treatment remain a challenge to clinicians. Thus, there is an urgent need to discover novel, less toxic, and more effective therapies for patients. Many vitamins and related chemicals, including vitamin E, (tocopherols) have shown their anti-cancer activities as anti-oxidants, activators of transcription factors or factors influencing epigenetic events. Although laboratory tests including the use of animal models showed that this vitamin may have anticancer properties, whether it can effectively prevent the development and/or progression of prostate cancer in humans remains to be intensively studied. This review provides up-to-date information regarding the recent outcomes of laboratory, epidemiology and/or clinical trials on the effects of tocopherols on prostate cancer development, along with our last observations on a combined treatment of a prostate cancer cell line (PC-3) with two natural antineoplastic compounds, naringenin (NG) and α-tocopherol (α-TOC). We report the synergic effect of α-TOC and NG in transglutaminase-induced differentiation of human PC-3 prostate cancer cells. While our results are based on one histological class of tumor, the most significant implication of this observation is that establishes a new way in the screening for detecting new differentiative antineoplastic agents.