A Cocktail of Natural Compounds Holds Promise for New Immunotherapeutic Potential in Head and Neck Cancer / 中国结合医学杂志

OBJECTIVE@#To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC).@*METHODS@#Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected.@*RESULTS@#Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production.@*CONCLUSIONS@#This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

Efecto quimioprotector del extracto alcaloideo de Melocactus bellavistensis (cactus globoso) sobre el cáncer de colon inducido con 1,2-dimetilhidrazina en ratas / Chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine

RESUMEN Objetivos Determinar la toxicidad y el efecto quimioprotector del extracto alcaloideo de Melocactus bellavistensis (cactus globoso) sobre el cáncer de colon inducido en ratas con 1,2 dimetilhidrazina (DMH). Materiales y métodos Se obtuvo el extracto alcaloideo de la parte carnosa de Melocactus bellavistensis, posteriormente, se realizó un ensayo de toxicidad aguda en 30 ratones de cepas Balb C57. Para evaluar su efecto quimioprotector se indujo el cáncer de colon en 45 ratas Holtzmann con DMH, según el siguiente diseño experimental: un grupo control con: polisorbato de sodio (PS) a 2 mL/kg y cuatro grupos con DMH 20 mg/kg más 0, 1, 5 y 10 mg/kg de extracto alcaloideo de Melocactus bellavistensis respectivamente. Resultados Con una muestra de 5 g de extracto alcaloideo se determinó una DL50 mayor a 1000 mg/mL en el ensayo de toxicidad aguda del extracto alcaloideo de Melocactus bellavistensis. Los resultados del efecto quimioprotector en los indicadores de estudio histopatológico revelaron que a las dosis de 5 y 10 mg/kg demostraron actividad antitumoral significativa en el cáncer de colon inducido por dimetilhidrazina en ratas con 100% de inhibición de neoplasia. Conclusiones En condiciones experimentales, el extracto de alcaloides de Melocactus bellavistensis demostró tener efecto quimioprotector en cáncer de colon inducido por dimetilhidrazina en ratas.

ABSTRACT Objectives To determine the toxicity and chemoprotective effect of the alkaloid extract of Melocactus bellavistensis against colon cancer induced in rats using 1,2-dimethylhydrazine (DMH). Materials and methods The alkaloid extract was obtained from the fleshy part of M. bellavistensis, and an acute toxicity test was then carried out on 30 mice of the Balb C57 strain. To assess its chemoprotective effect, colon cancer was induced in 45 Holtzman rats using DMH according to the following experimental design: one control group received 2 mL/kg sodium polysorbate, and four groups received 20 mg/kg DMH plus 0, 1, 5, or 10 mg/kg M. bellavistensis alkaloid extract. Results With a sample of 5 g of alkaloid extract, an LD50 greater than 1000 mg/mL was determined in the acute toxicity test. Histological indicators revealed that the 5 and 10 mg/kg doses had significant anti-tumor activity with 100% neoplasia inhibition against DMH- induced colon cancer in rats. Conclusions Under experimental conditions, the alkaloid extract of M. bellavistensis has a chemoprotective effect against DMH-induced colon cancer in rats.

The impacts of Elaeagnus umbellata Thunb. leaf and fruit aqueous extracts on mice hepatic, extrahepatic antioxidant and drug metabolizing enzymes related structures

ABSTRACT In this work, the potential chemopreventive activities of Elaeagnus umbellata fruit aqueous (EUFA) and leaf aqueous (EULA) extracts focusing on the modulatory influence of xenobiotic metabolizing enzymes (XMEs), antioxidant enzymes, glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), lactate dehydrogenase (LDH) activity, lipid peroxidation (LP), sulfhydryl groups were investigated in the hepatic and extrahepatic organs of Swiss albino mice (50 and 100 mg/kg body wt given orally for 14 days) and compared with BHA (0.75 % in diet). The modulatory and chemopreventive properties of two different doses EUFA and EULA were observed for cytochrome P450, cytochrome b5, sulfhydryl groups, NADPH-cytochrome P450 reductase, NADH-cytochrome b5 reductase, 7-ethoxyresorufin-deethylase and N,N-dimethylaniline N-oxidase activities in the liver and compared with BHA as a standard. The activities of glutathione S-transferase (GST) and DT-diaphorase (DTD) showed a significant increase in the kidney, forestomach, heart and brain at both doses of EUFA and EULA. The results of EULA-treated groups were found a notable increase in LDH, G6PD, 6PGD, GST and DTD activities. Superoxide dismutase level in liver, kidney and heart exhibited a significant increase at both doses of EULA. Glutathione reductase activity was a remarkable level at high dose of EUFA in liver, kidney and EULA in kidney. Both doses of EUFA were effective in inducing glutathione peroxidase activitiy in heart. The levels of LP at low and high doses of EULA-treated and EUFA-treated were effective in liver and kidney, respectively. The present results demonstrate that significant effects in the level of XMEs and antioxidant enzymes of EUFA and EULA are remarkable for modulating roles and natural chemoprevention properties and therefore is considered for a valuable natural source.

Alginate encapsulation in Glycyrrhiza glabra L.with phyto-chemical profiling of root extracts of in vitro converted plants using GC-MS analysis

Objective: To investigate the conversion potential of alginate encapsulated nodes of Glycyrrhiza glabra with phyto-chemical evaluation of root extract of field transferred plants. Methods: The excised axenic nodal segments were encapsulated in alginate matrix planted on Murashige and Skoog (1962) medium with different supplementation and formulations of PGRs.The two year old field transferred plants were evaluated for phyto-compounds analysis using GC-MS technique. Results: Varied responses were observed during the study, maximum conversion 95.83% ± 2.40% was obtained in these encapsulates when planted on MS medium containing 2.5 μM Kinetin and 0.5 μM α-Naphthalene acetic acid, which eventually developed into complete plantlets in a single step.Further,GC-MS analysis showed the presence of different phyto-compounds in the methanolic root extracts of in vitro con-verted plants. The results obtained revealed the presence of about 47 phyto-compounds along with various potential bioactive compounds useful for industrial and pharmaceu-tical purposes. Conclusions: This study investigates high frequency regeneration and conversion of Glycyrrhiza glabra in a single step in short time. Also, the in vitro raised plants are analysed for bioactive compounds after field transfer, which shows the presence of numerous compounds useful for commercial and pharmacological purposes.

Alginate encapsulation in Glycyrrhiza glabra L. with phyto-chemical profiling of root extracts of in vitro converted plants using GC-MS analysis

Objective To investigate the conversion potential of alginate encapsulated nodes of Glycyrrhiza glabra with phyto-chemical evaluation of root extract of field transferred plants. Methods The excised axenic nodal segments were encapsulated in alginate matrix planted on Murashige and Skoog (1962) medium with different supplementation and formulations of PGRs. The two year old field transferred plants were evaluated for phyto-compounds analysis using GC-MS technique. Results Varied responses were observed during the study, maximum conversion 95.83% ± 2.40% was obtained in these encapsulates when planted on MS medium containing 2.5 μM Kinetin and 0.5 μM α-Naphthalene acetic acid, which eventually developed into complete plantlets in a single step. Further, GC-MS analysis showed the presence of different phyto-compounds in the methanolic root extracts of in vitro converted plants. The results obtained revealed the presence of about 47 phyto-compounds along with various potential bioactive compounds useful for industrial and pharmaceutical purposes. Conclusions This study investigates high frequency regeneration and conversion of Glycyrrhiza glabra in a single step in short time. Also, the in vitro raised plants are analysed for bioactive compounds after field transfer, which shows the presence of numerous compounds useful for commercial and pharmacological purposes.

Antioxidant, cytotoxic and alpha-glucosidase inhibition activities from the Mexican berry "Anacahuita" (Cordia boissieri)

This study describes the total phenolic and flavonoid content as well as cytotoxic, alpha-glucosidase inhibition and antiradical/antioxidant potential of extracts obtained from the edible fruits of Cordia boissieri, which is widely distributed throughout northeastern Mexico. Phenolic and flavonoid content were evaluated by means of the Folin-Ciocalteu method and aluminum chloride colorimetric assay respectively. The antiradical/antioxidant activity was determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging and Trolox Equivalent Antioxidant Capacity (TEAC) assays. Cytotoxic activity was assessed by means of human cancer cell lines (MCF-7 and HeLa), alpha-glucosidase inhibition was determined by colorimetric assay using p-Nitrophenyl α-D-glucopyranoside (PNPG) as a substrate. Results indicate that extract of C. boissieri fruit has a good antioxidant potential to show a EC50: 137.76 ± 35 μg/mL and 65 ± 2 μM/g in the DPPH and TEAC assays respectively, inhibitor of the enzyme alpha-glucosidase involved in sugar uptake (IC50: 215.20 ± 35 μg/mL), cytotoxic activities against MCF-7 (IC50: 310 ± 42 μg/mL) and HeLa (IC50: 450.4 ± 21 μg/mL) cancer cell lines as well as an important phenolic content with 230 ± 23 mg/100g and 54± 11 mg/100g of phenols and flavonoids totals respectively. These results point towards an interesting potential for the fruits of C. boissieri as chemopreventive properties and expand the possibilities for agro-industrial uses(AU)

Este estudio describe el contenido de fenoles y flavonoides totales, el efecto citotóxico, la inhibición de la enzima alfaglucosidasa y el potencial antirradical/ antioxidante del extracto obtenidos a partir de los frutos de Cordia boissieri, especie distribuida por todo el noreste de México. El contenido de fenoles y flavonoides totales se determinó por medio de los métodos de Folin-Ciocalteu y cloruro férrico respectivamente. La actividad antirradical / antioxidante se determinó mediante el secuestro del radical libre 2,2-difenil-1-picrilhidrazil (DPPH) y el ensayo de Capacidad Antioxidante Equivalente al Trolox (CAET). La actividad citotóxica se evaluó sobre las líneas celulares de cáncer humano (MCF-7 y HeLa), para determinar la inhibición de la enzima alfa-glucosidasa se utilizó el ensayo colorimétrico utilizando como sustrato p-Nitrofenil-α-D-Glucopiranósido (PNPG). Los resultados indican que el extracto del fruto de C. boissieri tiene un buen contenido de antioxidantes al mostrar una CE50 de 137.76 ± 35 μg/mL y de 65 ± 2 μM/g en los ensayos de DPPH y CAET respectivamente, un efecto inhibitorio interesante sobre la enzima alfa-glucosidasa, implicadas en la absorción de azúcar (CI50: 215.20 ± 35 μg/mL), efecto citotóxico contra las células cancerosas MCF-7 (CI50: 310 ± 42 μg/mL) y HeLa (450.4 ± 21 μg/mL), así como un importante contenido compuestos fenólicos con 230 ± 23 mg / 100g y 54 ± 11 mg / 100 g de fenoles y flavonoides totales, respectivamente. Estos resultados sugieren el potencial del fruto de C. boissieri como una fuente importante de compuestos quimiopreventivos y amplían las posibilidades para su aprovechamiento agroindustrial(AU)

Hot water extract of Chlorella vulgaris induced DNA damage and apoptosis

OBJECTIVES: The aim of this study was to determine the antiproliferative and apoptotic effects of hot water extracts of Chlorella vulgaris on hepatoma cell line HepG2. INTRODUCTION: The search for food and spices that can induce apoptosis in cancer cells has been a major study interest in the last decade. Chlorella vulgaris, a unicellular green algae, has been reported to have antioxidant and anti-cancer properties. However, its chemopreventive effects in inhibiting the growth of cancer cells have not been studied in great detail. METHODS: HepG2 liver cancer cells and WRL68 normal liver cells were treated with various concentrations (0-4 mg/ml) of hot water extract of C. vulgaris after 24 hours incubation. Apoptosis rate was evaluated by TUNEL assay while DNA damage was assessed by Comet assay. Apoptosis proteins were evaluated by Western blot analysis. RESULTS: Chlorella vulgaris decreased the number of viable HepG2 cells in a dose dependent manner (p < 0.05), with an IC50 of 1.6 mg/ml. DNA damage as measured by Comet assay was increased in HepG2 cells at all concentrations of Chlorella vulgaris tested. Evaluation of apoptosis by TUNEL assay showed that Chlorella vulgaris induced a higher apoptotic rate (70 percent) in HepG2 cells compared to normal liver cells, WRL68 (15 percent). Western blot analysis showed increased expression of pro-apoptotic proteins P53, Bax and caspase-3 in the HepG2 cells compared to normal liver cells WRL68, and decreased expression of the anti-apoptotic protein Bcl-2. CONCLUSIONS: Chlorella vulgaris may have anti-cancer effects by inducing apoptosis signaling cascades via an increased expression of P53, Bax and caspase-3 proteins and through a reduction of Bcl-2 protein, which subsequently lead to increased DNA damage and apoptosis.

Ginger extract (Zingiber officinale) has anti-cancer and anti-inflammatory effects on ethionine-induced hepatoma rats

OBJECTIVE: To evaluate the effect of ginger extract on the expression of NFêB and TNF-á in liver cancer-induced rats. METHODS: Male Wistar rats were randomly divided into 5 groups based on diet: i) control (given normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline-deficient diet + 0.1 percent ethionine to induce liver cancer and v) choline-deficient diet + ginger extract (100mg/kg body weight). Tissue samples obtained at eight weeks were fixed with formalin and embedded in paraffin wax, followed by immunohistochemistry staining for NFêB and TNF-á. RESULTS: The expression of NFêB was detected in the choline-deficient diet group, with 88.3 ± 1.83 percent of samples showing positive staining, while in the choline-deficient diet supplemented with ginger group, the expression of NFêB was significantly reduced, to 32.35 ± 1.34 percent (p<0.05). In the choline-deficient diet group, 83.3 ± 4.52 percent of samples showed positive staining of TNF-á, which was significantly reduced to 7.94 ± 1.32 percent (p<0.05) when treated with ginger. There was a significant correlation demonstrated between NFêB and TNF-á in the choline-deficient diet group but not in the choline-deficient diet treated with ginger extract group. CONCLUSION: In conclusion, ginger extract significantly reduced the elevated expression of NFêB and TNF-á in rats with liver cancer. Ginger may act as an anti-cancer and anti-inflammatory agent by inactivating NFêB through the suppression of the pro-inflammatory TNF-á.

Effect of curcumin and resveratrol on the cell cycle regulation, apoptosis and inhibition of metastasis related proteins in HN-4 cells

Nontraditional or alternative medicine is becoming an increasingly attractive approach for the treatment of various inflammatory disorders and cancers. Curcumin is the major constitute of turmoric powder extracted from the rhizomes of the plant Curcuma longa. Resveratrol is a phytoalexin present in grapes and a variety of medicinal plants. In this report, We investigated the effect of curcumin and resveratrol on regulatory protein of cell cycle, induction of apoptosis and MMP activity. Treatment with 75 M curcumin for 24 hrs produced morphological changing in HN-4 cells. Curcumin and resveratrol inhibited the cellular growth in HN-4 cells. Inhibition of cell growth was associated with down-regulation of cell cycle regulatory proteins. Curcumin-induced caspase-3 activation and Bax degradation were dose-dependent with a maximal effect at a concentration of 100 M. The elevated caspase-3 activity in curcumin treated HN-4 cells are correlated with down-regulation of survivin and cIAP1, but not cIAP2. Curcumin induced a dose-dependent increase of cytochrome c in the cytosol. Curcumin induced-apoptosis was mediated through the release of cytochrome c. In addition, curcumin-induced apoptosis was caused by the generation of reactive oxygen species, which was prevented by antioxidant N-acetyl-cysteine (NAC). Cotreatment with NAC markedly prevented cytochrome c release, Bax cleavage and cell death. Also resveratrol-induced apoptosis was preceded by down-regulation of the anti-apoptotic Bcl-2, cIAP1, and caspase-3 activity. However, resveratrol-induced apoptosis was not prevented by antioxidant NAC. In addition, HN-4 cells release basal levels of MMP2 when cultured in serum-free medium. Treatment of the cells with various concentrations of PMA for 24 hr induced the expression and secretion of latent MMP9 as determined by gelatin zymography. HN-4 cells were treated with various concentrations of curcumin and resveratrol in the presence of 75 nM PMA, and MMP2 and 9 activities were inhibited by curcumin and resveratrol. These findings have implications for developing curcumin-based anticancer and anti-inflammation therapies.

Effect of resveratrol on coxsackie virus B3m-induced mycocarditis in mice / 中成药

Objective: To observe the intervening effect of resveratrol on coxsackie virus B3m-induced mycocarditis in Balb/c mice and explore its mechanism. Methods: An animal model of viral mycocarditis induced by coxsackie virus B3m (CVB3m) was used, taking ribavirin as control drug, to examine the changes of general condition, mortality, the weights of heart, liver and spleen, serum MDA and NO levels, and cardiac histology in Balb/c mice. Results: By comparison with ribavirin, it was found that in the mice model of viral mycocarditis induced by coxsackie virus B3m resveratrol significantly improved the changes of general condition, mortality, the weights of heart, liver and spleen, serum MDA and NO levels, and cardiac histology. Conclusion: It suggested that resveratrol might have some chemopreventive and chemotherapeutic effects in the treatment of viral mycocarditis.