The anticancer effects of biodegradable nanomagnetic dual natural components on the leptin gene expression in lung cancer.

Lung cancer is an invasive and progressive, fatal disease with few treatment choices and poor overall survival rates in nonsurgical stages. Leptin (LEP), an adipocyte derivative cytokine, participates in carcinogenesis. Increased amounts of systemic and pulmonary LEP indicate lung cancer. Curcumin (CUR) and silibinin (SIL) are herbal compounds which have many anticancer properties, but they have hydrophobic structures and low solubility in water. In this study, evaluated CUR-SIL dual drug-loaded poly (ɛ-caprolactone) [PCL]-co-poly ethylene glycol (PEG) magnetic nanoparticles (MNPs) were used to determine the inhibitory effect on LEP gene expression. The physicochemical properties of free and CUR-SIL-loaded PCL-PEG were fully characterized. The cytotoxic effect of CUR-SIL-loaded PCL-PEG magnetic nanoparticles was determined by MTT assay. Afterward, the inhibition of LEP gene expression was specified through real-time PCR. Results indicated that CUR-SIL cytotoxicity is time- and dose-dependent. CUR-SIL loaded MNPs showed the IC50 limit in lower concentrations in comparison to net CUR-SIL. CUR-SIL loaded MNPs reduced LEP expression more than net CUR-SIL. These results revealed the possibilities of CUR-SIL-loaded MNPs as a natural and effective antitumor drug delivery system to fight lung tumors.

Comparison of inhibitory effect of 17-DMAG nanoparticles and free 17-DMAG in HSP90 gene expression in lung cancer.

BACKGROUND: Up-regulation of hsp90 gene expression occurs in numerous cancers such as lung cancer. D,L-lactic-co-glycolic acid-poly ethylene glycol-17-dimethylaminoethylamino-17-demethoxy geldanamycin (PLGA-PEG-17DMAG) complexes and free 17-DMAG may inhibit the expression. The purpose of this study was to examine whether nanocapsulating 17DMAG improves the anti cancer effect over free 17DMAG in the A549 lung cancer cell line. MATERIALS AND METHODS: Cells were grown in RPMI 1640 supplemented with 10% FBS. Capsulation of 17DMAG is conducted through double emulsion, then the amount of loaded drug was calculated. Other properties of this copolymer were characterized by Fourier transform infrared spectroscopy and H nuclear magnetic resonance spectroscopy. Assessment of drug cytotoxicity on the grown of lung cancer cell line was carried out through MTT assay. After treatment, RNA was extracted and cDNA was synthesized. In order to assess the amount of hsp90 gene expression, real-time PCR was performed. RESULTS: In regard to the amount of the drug load, IC50 was significant decreased in nanocapsulated(NC) 17DMAG in comparison with free 17DMAG. This was confirmed through decrease of HSP90 gene expression by real-time PCR. CONCLUSIONS: The results demonstrated that PLGA-PEG-17DMAG complexes can be more effective than free 17DMAG in down-regulating of hsp90 expression by enhancing uptake by cells. Therefore, PLGA-PEG could be a superior carrier for this kind of hydrophobic agent.

Comparison of inhibitory effects of 17-AAG nanoparticles and free 17-AAG on HSP90 gene expression in breast cancer.

BACKGROUND: HSP90 may be overexpressed in cancer cells which are greatly dependent on Hsp90 function. Geldanamycin derivative 17 allylamino-17-demethoxygeldanamycin (17-AAG) inhibits the function and expression of HSP90. 17-AAG has poor water-solubility which is a potential problem for clinical practice. In this study for improving the stability and solubility of molecules in drug delivery systems we used a ß-cyclodextrin- 17AAG complex. MATERIALS AND METHODS: To assess cytotoxic effects of ß-cyclodextrin-17AAG complexes and free 17AAG, colorimetric cell viability (MTT) assays were performed. Cells were treated with equal concentrations of ß-cyclodextrin- 17AAG complex and free 17AAG and Hsp90 gene expression levels in the two groups was compared by real-time PCR. RESULTS: MTT assay confirmed that ß-cyclodextrin- 17AAG complex enhanced 17AAG cytotoxicity and drug delivery in T47D breast cancer cells. The level of Hsp90 gene expression in cells treated with ß-cyclodextrin- 17AAG complex was lower than that of cells treated with free 17AAG (P=0.001). CONCLUSIONS: The results demonstrated that ß-cyclodextrin- 17AAG complexes are more effective than free 17AAG in down-regulating HSP90 expression due to enhanced ß-cyclodextrin-17AAG uptake by cells. Therefore, ß-cyclodextrin could be superior carrier for this kind of hydrophobic agent.

ABT-737, Synergistically Enhances Daunorubicin-Mediated Apoptosis in Acute Myeloid Leukemia Cell Lines.

PURPOSE: Intensive chemotherapy with daunorubicin (DNR) is associated with serious side effects in acute myeloid leukemia (AML) patients. In this study the effect of small-molecule BH3-mimetic, ABT-737, on the sensitivity of HL60 and U937 AML cell lines was investigated. METHODS: The cytotoxic effects of DNR and ABT-737, alone or in combination were assessed using MTT assay and combination index analysis. The effects of treatments on the cell proliferation was determined by trypan blue assay. ELISA cell death assay was used for measurement of apoptosis. RESULTS: IC50 values of DNR and ABT-737 were 2.52 and 0.59 µM for HL-60 cells line and 1.31 and 0.80 µM for U937 cell line at 24 h, respectively. Surprisingly, combination treatment significantly lowered the IC50 values in a synergic manner in both cell lines. Moreover, treatment with a mixture of two agents had more growth inhibition effect relative to the monotherapy. RESULTS of apoptosis assay showed that the cytotoxic effects are related to the enhancement of apoptosis. CONCLUSION: Our study suggests that ABT-737 synergistically enhances the cytotoxic effect of DNR in AML cell lines and therefore may be useful to overcome chemoresistance of leukemia patients.

Plasma Leptin, hTERT Gene Expression, and Anthropometric Measures in Obese and Non-Obese Women with Breast Cancer.

INTRODUCTION: Expression of human telomerase reverse transcriptase (hTERT) occurs in most cancers but its relation with obesity is unclear. This study explores the association between leptin levels and anthropometric indices with hTERT mRNA levels in breast cancer patients of different obesity grades. MATERIALS AND METHODS: In this case-control study, 65 breast cancer patients participated. Expression of tissues hTERT mRNA was carried out by real-time reverse transcription polymerase chain reaction. Leptin concentrations were measured by enzyme-linked immunoassay. RESULTS: Twelve patients (18.46%) were hTERT negative and 53(81.54%) were positive. hTERT mRNA levels were associated with BMI but not with waist circumference (WC) (r = 0.219, P = 0.22) and waist to hip ratio (WHR) (r = 0.212, P = 0.237). Leptin level and hTERT mRNA levels (r = 0.484, P = 0.008) were correlated as well as BMI and hTERT expression. CONCLUSIONS: This study has shown a correlation between leptin levels and hTERT expression. These findings may clarify the role of leptin in breast carcinogenesis, and hence obesity could be responsible for increased incidences in breast cancer as well as its progression via enhanced production of leptin.