Combination effect of doxorubicin and HIF inhibitor on MCF-7 CD44+/CD24- subpopulation cells in hypoxic condition

Abstract Hypoxia-inducible factors (HIFs) and cancer stem cells (CSCs) are two challenging causes of radiotherapy and chemotherapy resistance, leading to most cases of failure and recurrence in breast cancer therapy. This study was conducted to investigated the inhibitory effect of combination therapy with doxorubicin (an anthracycline) and FM19G11 (an HIF inhibitor) on MCF-7 cells and their CSC-like cells (CSC-LCs). MCF-7 CSC-LCs with a CD44+/CD24- phenotype were sorted and characterized by flow cytometry. A combination of doxorubicin and FM19G11 caused more cytotoxic effects on MCF-7 and CSC-LCs compared to doxorubicin monotherapy. The largest synergistic effect was observed in CSC-LCs under hypoxic conditions; however, MCF-7 cells showed no synergism in normoxic conditions. The administration of doxorubicin and FM19G11 induced late apoptotic and necrotic cell death in MCF-7 and CSC-LCs. Additionally, G2 phase arrest was observed in both cells. Our results demonstrated that co-administration of FM19G11 and doxorubicin had a synergistic effect in hypoxia and improved drug resistance in breast cancer stem cells.

[Effect of HESA-a on acute pomyelocytic cell line[NB4]]

Acute leukemia is one of the main causes of cancer in the world. Now a days using natural materials as source of anticancer drugs is more recommended. HESA-A is a drug of herbal-marine origin [patented by Iranian researcher]. HESA-A is composed of 50% inorganic substance? 45% organic substance [aminoenthraquinone] and 5% water. In this study effects of HESA-A? on NB4 cell line [Acute promyelocytic leukemia cells] was evaluated. HESA-A was prepared in normal saline as a stock solution [80 mg/ml, PH=7.4], and then was sterilized. After culturing and proliferation of NB4 cell line, the cells were treated by doses of 1, 2, 4 and 8 mg/ml of HESA-A. Respectively after 72h, the percentage of viable and dead cells were counted by using Trypan blue staining in Neubanr hemocytometer. Then by MTTassay, the percentage of cell survival were determined by ELISA reader in 570nm. Finally the effects of HESA-A on apoptosis were evaluated by flocytometery. This in vitro study shows that HESA-A has a cytotoxcic and antiprolifrative effects against NB4 cell line [Dose dependent].IC50 dose was 5mg/ml .HESA-A can result in apoptosis in 50% of the cells. Although the mechanism of HESA-A cytotoxicity action is not known, yet this study shows that this drug may cause apoptosis of cells by dose dependent method

Effect of ProRoot MTA, Portland cement, and amalgam on the expression of fibronectin, collagen I, and TGFβ by human periodontal ligament fibroblasts in vitro.

Context: Today many materials have been introduced for root-end filling materials. One of them is mineral trioxide aggregate (MTA) that is mentioned as a gold standard. Aims: The purpose of this in vitro study was to evaluate the reaction of human periodontal ligament fibroblasts to the root-end filling materials, such as ProRoot MTA, Portland cement, and amalgam. Settings and Design: Eight impacted teeth were extracted in aseptic condition. The tissues around the roots were used to obtain fibroblast cells. After cell proliferation, they were cultured in the chamber slides and the extracts of the materials were added to the wells. Materials and Methods: Immunocytochemical method for measuring the expression of Fibronectin, collagen I and transforming growth factor beta (TGF®) was performed by Olysia Bioreport Imaging Software. Statistical Analysis Used: The results were analyzed by SPSS 13.0 and Tukey post hoc test with P<0.05 as the limit of significance. Results: Collagen expression in MTA specimens was higher than the other groups in 24 h significantly. After 48 h, the Portland cement group showed the most expression of collagen significantly and after 1 week, Portland cement and MTA groups had the most expression of collagen but there was no significant difference between these 2 groups. After 1 week, the Portland cement group demonstrated a higher amount of TGF® and fibronectin. Conclusions: The results suggest that Portland cement can be used as a less expensive root filling material with low toxicity. It has better effects than amalgam on the fibroblasts.

Cytotoxic activity of some marine brown algae against cancer cell lines

The aim of this study was to investigate the in vitro cytotoxic activity of total extract of MeOH (70 percent) and partition fractions of hexan, chloroform (CHCL3), ethylacetate (EtOAc) and MeOH-H2O of brown algae species (Sargassum swartzii, Cystoseira myrica, Colpomenia sinuosa) found in the Persian Gulf against in different cell lines including HT-29, Caco-2, T47D, MDA-MB468 and NIH 3T3 cell lines by MTT and AnnexinV-PI assay. The hexan fraction of S. swartzii and C. myrica showed selective cytotoxicity against proliferation of Caco-2 cells (IC50<100 μg/ml) T47D cell line (IC50<100 μg/ml), respectively. S. swartzii and C. myrica were also observed for increasing apoptosis in Caco-2 and T47D cells. Total extract and fractions of C. sinuosa did not show any significant cytotoxicity against the studied cell lines. MDA-MB468 cells were more sensitive to C. myrica than was T47D (IC50 99.9±8.11 vs. 56.50‘± 0.88). This reflects an estrogen receptor independent mechanism for cytotoxicity of the extract. The IC50 of the hexan fraction of C. myrica on T47D parent cells was lower than it was on T47D-TR cells (IC50 99.9±8.11 vs. 143.15 ± 7.80). This finding suggests a role for the MDR-1 in the development of possible future tolerance to the extract.