Growth Inhibition and Apoptotic Effect of Pine Extract and Abietic Acid on MCF-7 Breast Cancer Cells via Alteration of Multiple Gene Expressions Using In Vitro Approach.

In vitro anti-proliferative activity of Pinus palustris extract and its purified abietic acid was assessed against different human cancer cell lines (HepG-2, MCF-7 and HCT-116) compared to normal WI-38 cell line. Abietic acid showed more promising IC50 values against MCF-7 cells than pine extract (0.06 µg/mL and 0.11 µM, respectively), with insignificant cytotoxicity toward normal fibroblast WI-38 cells. Abietic acid triggered both G2/M cell arrest and subG0-G1 subpopulation in MCF-7, compared to SubG0-G1 subpopulation arrest only for the extract. It also induced overexpression of key apoptotic genes (Fas, FasL, Casp3, Casp8, Cyt-C and Bax) and downregulation of both proliferation (VEGF, IGFR1, TGF-ß) and oncogenic (C-myc and NF-κB) genes. Additionally, abietic acid induced overexpression of cytochrome-C protein. Furthermore, it increased levels of total antioxidants to diminish carcinogenesis and chemotherapy resistance. P. palustris is a valuable source of active abietic acid, an antiproliferative agent to MCF-7 cells through induction of apoptosis with promising future anticancer agency in breast cancer therapy.

Morphological alterations in the jejunal mucosa of aged rats and the possible protective role of green tea.

INTRODUCTION: Gastrointestinal disorders become more prevalent with ageing. This study is aimed to describe morphological changes that occur in the jejunal mucosa of male albino rats as a result of ageing and the protec-tive effect of green tea (GT) extract. MATERIAL AND METHODS: The experiment was performed on sixty rats: thirty young-adult (6-month old, body mass 200-220 g) and thirty old (24-month-old, body mass 220-260 g) animals. Each group was further divided into two subgroups (n = 15 each): control rats and GT-treated rats that received 1.5 mL (300 mg/kg/day) of GT extract for 14 weeks by oral gavage. Sections of the jejunum were stained with hematoxylin and eosin, periodic acid Schiff, toluidine blue and Mallory trichrome methods. The presence of proliferating cell nuclear antigen (PCNA)- and CD68-positive cells was evaluated by immunohistochemical staining. Ultrathin sections were prepared and examined by a transmission electron microscope (TEM). RESULTS: Jejunal sections of the old control rats showed distortion of submucosa and attenuated muscularis externa with decreased height of intestinal villi. The villi also showed partial loss of acidophilic brush border with wide spaces between enterocytes. Swollen, short, blunt or broad villi with abundant mononuclear cell infiltration of lamina propria and congested blood vessels were evident both by light and electron microscopy. The number of PCNA- and CD68-positive cells in jejunal mucosa of old rats was higher than in young rats. The activity of glutathione peroxidase (GPX) and total antioxidant capacity (TAC) in the mucosa of old control rats were lower, whereas malondialdehyde (MDA) levels were higher in the jejunal homogenates of old rats as compared to young control rats. Administration of GT extract protected the jejunal mucosa from age-related changes by restoring its histological structure. The treatment of old rats with GT extract significantly decreased MDA levels in the jejunum and increased TAC and GPX activity. CONCLUSIONS: The age-related changes of the morphology of rat jejunum could be ameliorated by prolonged supplementation of the green tea extract.

Tiron ameliorates oxidative stress and inflammation in a murine model of airway remodeling.

Airway remodeling includes lung structural changes that have a role in the irreversibility of pulmonary dysfunction shown in chronic bronchial asthmatics. The current experiment investigated the effect of the mitochondrial antioxidant, tiron in comparison with dexamethasone (DEXA) on airway remodeling in chronic asthma. Sensitized BALB/c mice were challenged with ovalbumin (OVA) aerosol for 8weeks, OVA sensitized-challenged mice were treated with either DEXA or tiron, respectively. After that, lung tissue and bronchoaveolar lavage fluid (BALF) were used for measurement of different biological markers. Lungs were examined for histopathological changes and immunohistochemistry. Upon comparing with vehicle treated animals, trion or DEXA treatment significantly reduced eosinophils, lymphocytes, neutrophils and macrophages count in the BALF. Both drugs significantly alleviated chronic OVA-induced oxidative stress as illustrated by decreased pulmonary malondialdenhyde (MDA) and increased glutathione (GSH) and superoxide dismutase (SOD) levels. Asthmatic mice exhibited elevated levels of NOx, IL-13 and TGF-ß1 that were reduced by DEXA and tiron. Histopathological changes and increased immunoreactivity of nuclear factor-Kappa B (NF-κ B) in OVA-challenged mice were minimized by tiron and DEXA treatment. In conclusion, in this model of chronic asthma DEXA and tiron ameliorated airway remodeling and inflammation in experimental chronic asthma with no difference between the effect of tiron and DEXA. Tiron has a potential role as adjuvant treatment in chronic asthma.