The NF-kappa B inhibitor, celastrol, could enhance the anti-cancer effect of gambogic acid on oral squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Gambogic acid (GA) is a major active ingredient of gamboge, a widely used traditional Chinese medicine that has been reported to be a potent cytotoxic agent against some malignant tumors. Many studies have shown that the NF-kappa B signaling pathway plays an important role in anti-apoptosis and the drug resistance of tumor cells during chemotherapy. In this study, the effects and mechanisms of GA and the NF-kappa B inhibitor celastrol on oral cancer cells were investigated.</p> <p>Methods</p> <p>Three human oral squamous cell carcinoma cell lines, Tca8113, TSCC and NT, were treated with GA alone, celastrol alone or GA plus celastrol. Cytotoxicity was assessed by MTT assay. The rate of apoptosis was examined with annexin V/PI staining as well as transmission electronic microscopy in Tca8113 cells. The level of constitutive NF-kappa B activity in oral squamous cell carcinoma cell lines was determined by immunofluorescence assays and nuclear extracts and electrophoretic mobility shift assays (EMSAs) <it>in vitro</it>. To further investigate the role of NF-kappa B activity in GA and celastrol treatment in oral squamous cell carcinoma, we used the dominant negative mutant SR-IκBα to inhibit NF-kappa B activity and to observe its influence on the effect of GA.</p> <p>Results</p> <p>The results showed that GA could inhibit the proliferation and induce the apoptosis of the oral squamous cell carcinoma cell lines and that the NF-kappa B pathway was simultaneously activated by GA treatment. The minimal cytotoxic dose of celastrol was able to effectively suppress the GA-induced NF-kappa B pathway activation. Following the combined treatment with GA and the minimal cytotoxic dose of celastrol or the dominant negative mutant SR-IκBα, proliferation was significantly inhibited, and the apoptotic rate of Tca8113 cells was significantly increased.</p> <p>Conclusion</p> <p>The combination of GA and celastrol has a synergistic antitumor effect. The effect can be primarily attributed to apoptosis induced by a decrease in NF-kappa B pathway activation. The NF-kappa B signaling pathway plays an important role in this process. Therefore, combining GA and celastrol may be a promising modality for treating oral squamous cell carcinoma.</p

Evidence-based assessment of antiosteoporotic activity of petroleum-ether extract of Cissus quadrangularis Linn. on ovariectomy-induced osteoporosis

The increasing incidence of postmenopausal osteoporosis and its related fractures have become global health issues in the recent days. Postmenopausal osteoporosis is the most frequent metabolic bone disease; it is characterized by a rapid loss of mineralized bone tissue. Hormone replacement therapy has proven efficacious in preventing bone loss but not desirable to many women due to its side-effects. Therefore we are in need to search the natural compounds for a treatment of postmenopausal symptoms in women with no toxic effects. In the present study, we have evaluated the effect of petroleum-ether extract of Cissus quadrangularis Linn. (CQ), a plant used in folk medicine, on an osteoporotic rat model developed by ovariectomy. In this experiment, healthy female Wistar rats were divided into four groups of six animals each. Group 1 was sham operated. All the remaining groups were ovariectomized. Group 2 was fed with an equivolume of saline and served as ovariectomized control (OVX). Groups 3 and 4 were orally treated with raloxifene (5.4 mg/kg) and petroleum-ether extract of CQ (500 mg/kg), respectively, for 3 months. The findings were assessed on the basis of animal weight, morphology of femur, and histochemical localization of alkaline phosphatase (ALP) (an osteoblastic marker) and tartrate-resistant acid phosphatase (TRAP) (an osteoclastic marker) in upper end of femur. The study revealed for the first time that the petroleum-ether extract of CQ reduced bone loss, as evidenced by the weight gain in femur, and also reduced the osteoclastic activity there by facilitating bone formation when compared to the OVX group. The osteoclastic activity was confirmed by TRAP staining, and the bone formation was assessed by ALP staining in the femur sections. The color intensity of TRAP and ALP enzymes from the images were evaluated by image analysis software developed locally. The effect of CQ was found to be effective on both enzymes, and it might be a potential candidate for prevention and treatment of postmenopausal osteoporosis. The biological activity of CQ on bone may be attributed to the phytogenic steroids present in it

Mel e açúcar mascavo na cicatrização de feridas Honey and brown sugar in wounds healing

O estudo teve como objetivo comparar a eficácia do mel e do açúcar mascavo na cicatrização de feridas induzidas cirurgicamente na pele de cobaias, para avaliar o tempo de cicatrização, as variações macroscópicas e microscópicas do tecido cicatricial, a contração das feridas e o grau de contaminação. Quinze cobaias da raça Abissínia, machos inteiros, de seis meses de idade e pesando entre 500 a 850 gramas, foram divididas em três grupos com cinco animais cada, nos quais foram induzidas, cirurgicamente, três feridas em cada animal com dimensão de 1,5cm² e distância entre elas de 1,5cm, na região dorsal. A ferida F1 foi tratada diariamente com mel, a ferida F2 com solução salina 0,9% (controle) e a ferida F3 com o açúcar mascavo. A eutanásia foi realizada no Grupo 1 ao sétimo dia após a cirurgia, no Grupo 2 ao décimo quarto dia e no Grupo 3 no vigésimo primeiro dia após a cirurgia, sendo as biópsias encaminhadas para avaliação histopatológica. Foram também realizados swabs das feridas em todos os grupos no terceiro e sétimo dias após a cirurgia e as amostras enviadas para a cultura e isolamento bacteriano. Concluiu-se que as feridas tratadas com o mel cicatrizaram mais rápido em relação às tratadas com o açúcar mascavo, demonstrando a maior propriedade cicatrizante do mel em relação ao açúcar mascavo.<br>The study aimed to compare the effectiveness of honey and brown sugar in wounds healing induced in the skin of guinea pigs, to evaluate the healing time, microscopic and macroscopic healing variations, wound contraction and contamination degree. Fifteen guinea pigs, Abyssinia breed, males, six months of age and weighing between 500 to 850 grams, were divided in three groups with five animals each. Three wounds were promoted in each animal, surgical, with 1.5cm² and 1.5cm between them, in the dorsal region. The F1 was treated, daily, with honey, F2 with saline solution 0,9% (control) and F3 with brown sugar. Euthanasia was performed in Group 1 on the seventh day after the surgery, Group 2 on the fourteenth day and the Group 3 on the twenty-first day after the surgery and the biopsies sent to histopathological evaluation. Wounds swabs were made in all groups on the third and seventh days after the surgery and the samples sent for culture and bacterial isolation. The wounds treated with honey healed faster than treated with brown sugar