beta-carotene and Bone-Neoplasms

To evaluate efficacy of oral antioxidant treatment given to patients before radiologic procedures in reducing x-ray-induced DNA damage.. There was a significantly higher number of gamma-H2AX foci/cell after ionization radiation in the control group compared with the antioxidant group (P = .009). There was no statistically significant difference in number of gamma-H2AX foci/cell before or after exposure in the antioxidant group; the number of gamma-H2AX foci/cell was statistically significantly higher (P = .009) in the control group after exposure to. In patients undergoing

Topics: Acetylcysteine; Administration, Oral; Adult; Aged; Aged, 80 and over; Antioxidants; Ascorbic Acid; beta Carotene; Biomarkers; Bone Neoplasms; DNA Breaks, Double-Stranded; Drug Combinations; Histones; Humans; Leukocytes, Mononuclear; Male; Middle Aged; Neoplasm Staging; Ontario; Oxidative Stress; Predictive Value of Tests; Prospective Studies; Radiation Injuries; Radiopharmaceuticals; Technetium Tc 99m Medronate; Thioctic Acid; Time Factors; Treatment Outcome

The safety of antioxidant supplementation during radiation therapy (RT) for cancer is controversial. Antioxidants could potentially counteract the pro-oxidant effects of RT and compromise therapeutic efficacy. We performed a prospective study nested within the Physicians' Health Study (PHS) randomized trial to determine if supplemental antioxidant use during RT for prostate cancer is associated with an increased risk of prostate cancer death or metastases.. PHS participants (383) received RT for prostate cancer while randomized to receive beta-carotene (50 mg on alternate days) or placebo. The primary endpoint was time from RT to lethal prostate cancer, defined as prostate cancer death or bone metastases. The Kaplan-Meier method was used to estimate survival probabilities and the log-rank test to compare groups. Cox proportional hazards regression was used to estimate the effect of beta-carotene compared with that of placebo during RT.. With a median follow-up of 10.5 years, there was no significant difference between risk of lethal prostate cancer with the use of beta-carotene during RT compared with that of placebo (hazard ratio = 0.72; 95% confidence interval [CI], 0.42-1.24; p = 0.24). After we adjusted for age at RT, prostate-specific antigen serum level, Gleason score, and clinical stage, the difference remained nonsignificant. The 10-year freedom from lethal prostate cancer was 92% (95% CI, 87-95%) in the beta-carotene group and 89% (95% CI, 84-93%) in the placebo group.. The use of supplemental antioxidant beta-carotene during RT was not associated with an increased risk of prostate cancer death or metastases. This study suggests a lack of harm from supplemental beta-carotene during RT for prostate cancer.

Topics: Aged; Antioxidants; beta Carotene; Bone Neoplasms; Cause of Death; Double-Blind Method; Humans; Male; Neoplasm Grading; Neoplasm Recurrence, Local; Neoplasm Staging; Prospective Studies; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Radiation Tolerance; Treatment Outcome

We previously demonstrated that SAOS human osteosarcoma cells, incubated with carotenoid-enriched nanoemulsions (CEN), activated a nonprotective form of autophagy and delayed cell proliferation. The present work focuses on the biological effects of CEN on a derivative of SAOS cells named SAOS400, recently described for their radiation resistance and higher expression of therapy-induced senescence (TIS) markers. SAOS400 cells, incubated with CEN, activated a “cytostatic” form of autophagy confirmed by cell cycle arrest in the G2/M phase and increased expression of autophagic proteins. Treatment of SAOS400 cells with CEN also resulted in decreased expression of the senescence marker p16INK4. However, when SAOS400 cells were γ-irradiated in combination with CEN, the threshold for cell death was reached (>60% after 96 h). We showed that this type of cell death corresponded to ‘cytotoxic’ or ‘lethal’ autophagy and that the combined treatment of CEN plus γ-rays was synergistic, with the combination index < 1. Since CEN contained β-carotene, the pure compound was used in SAOS400 cells at the same concentration present in CEN and up to 10 times higher. However, no radio-sensitizing effect of β-carotene was observed, suggesting that the biological effect of CEN was due to less abundant but more bioactive molecules, or to the synergistic activity of multiple components present in the extracts, confirming the functional pleiotropy of natural extracts enriched in bioactive molecules.

Topics: Apoptosis; Autophagy; beta Carotene; Bone Neoplasms; Carotenoids; Cell Death; Cell Line, Tumor; Cell Proliferation; Humans; Osteosarcoma

Survival of osteosarcoma patients hinges on prevention or treatment of recurrent and metastatic lesions. Therefore, novel chemotherapeutics for more effective treatment and prevention of this disease are required. Carotenoids are natural pigments and exhibit various biological functions. We evaluated the anti-osteosarcoma properties of several carotenoids. Among carotenoids, fucoxanthin and its metabolite fucoxanthinol, inhibited the cell viability of osteosarcoma cell lines. Fucoxanthinol induced G1 cell cycle arrest by reducing the expression of cyclin-dependent kinase 4, cyclin-dependent kinase 6 and cyclin E and apoptosis by reducing the expression of survivin, XIAP, Bcl-2 and Bcl-xL. Apoptosis was associated with activation of caspases-3, -8 and -9. In addition, fucoxanthinol inhibited the phosphorylation of phosphoinositide-dependent kinase 1 and Akt and the downstream glycogen synthase kinase 3β, resulting in downregulation of β-catenin. Fucoxanthinol inhibited the cell migration and invasion of osteosarcoma cells. It also reduced matrix metalloproteinase-1 expression and the activator protein-1 signal. Treatment of mice inoculated with osteosarcoma cells with fucoxanthin inhibited the development of osteosarcoma in mice. Fucoxanthin and fucoxanthinol inhibit cell growth, migration and invasion and induce apoptosis of osteosarcoma cells at least in part by inhibiting Akt and activator protein-1 pathways. Our findings provide a rationale for clinical evaluation of these novel agents in osteosarcoma.

Topics: Animals; Antineoplastic Agents; beta Carotene; Bone Neoplasms; Carotenoids; Cell Proliferation; Cell Survival; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Humans; Mice; Osteosarcoma; Proto-Oncogene Proteins c-akt; Xanthophylls

Serum antioxidant vitamins A (retinol) and E (alpha-tocopherol), beta-carotene, zinc, and selenium, and cholesterol and related proteins for 170 children with newly diagnosed malignancy were measured at diagnosis and 6 months after initiation of treatment, and compared with those of 632 cancer-free controls. Incident cancer cases and controls were 1-16 years old and recruited between 1986 and 1989. At diagnosis, age- and sex-adjusted serum concentrations of retinol, beta-carotene, zinc, and alpha-tocopherol were significantly inversely associated with cancer. No significant decreases in mean values were observed at 6 month, except for the alpha-tocopherol-to-cholesterol ratio in patients with bone tumors and serum zinc in bone tumors and central nervous system malignancies. An increase during the period of treatment was found for retinol and selenium in leukemia patients. beta-carotene was maintained at the initial concentrations determined prior to therapy. These findings provide further information about micronutrient requirements in children with cancer.

Topics: Adolescent; Antioxidants; beta Carotene; Bone Neoplasms; C-Reactive Protein; Case-Control Studies; Central Nervous System Neoplasms; Child; Child, Preschool; Cholesterol; Chromatography, High Pressure Liquid; Female; Follow-Up Studies; Humans; Immunoglobulins; Infant; Leukemia; Male; Micronutrients; Neoplasms; Pilot Projects; Selenium; Serum Albumin; Vitamin A; Vitamin E; Zinc