Application of dextran-coated iron oxide nanoparticles in enhancing the radiosensitivity of cancerous cells in radiotherapy with high-energy electron beams

Purpose: Nowadays, cancer is one of the most important causes of morbidity and mortality in the world. The ideal aim of radiotherapy is delivering a lethal radiation dose to tumor cells while minimizing radiation exposure to healthy tissues around the tumor. One way to increase the dose in the tumor cells is the use of high-atomic number nanoparticles as radiosensitizer agents in these cells. The aim of this in vitro study was investigating the radiosensitization enhancement potential of the dextran-coated iron oxide nanoparticles (IONPs) on HeLa and MCF-7 cell lines in irradiations with high-energy electron beams. Materials and Methods: In this in vitro study, the cytotoxicity level of dextran-coated IONPs at different concentrations (10, 40, and 80 μg/ml) was assessed on HeLa and MCF-7 cell lines. To evaluate the radiosensitivity effect, the nanoparticles were incubated with the cells at different concentrations for 24 h and afterward irradiated with different doses (0, 2, 4, 6, and 8 Gy) of 6 and 12 MeV electron beams. The cells survival fractions were obtained by the methylthiazoletetrazolium assay. Results: Toxicity results of the nanoparticles at 10 and 40 μg/ml concentrations showed no significant cytotoxicity effect. The cells survival rates in groups receiving radiation in the absence and presence of IONPs showed a significant difference. The radiosensitivity enhancement induced by the nanoparticles in MCF-7 cell line was more than it in HeLa cell line. The average of radiosensitization enhancement factor at 10, 40, and 80 μg/ml concentrations and under 6 MeV irradiations obtained as 1.13, 1.19, 1.25, and 1.26, 1.28, 1.29 for HeLa, and MCF-7 cells, respectively. When 12 MeV electron beams were carried out, the values of 1.17, 1.26, 1.32, and 1.29, 1.32, 1.35 were obtained for the cells at the mentioned concentrations, respectively. Furthermore, the significant differences were observed in radiosensitization enhancement between 6 and 12 MeV electron beams irradiations. Conclusion: Use of dextran-coated IONPs can increase radiosensitivity and consequently at a given absorbed dose more cell killing will occur in cancerous cells. In other words, these nanoparticles can improve the efficiency of electron therapy

Intracellular GSH alterations and its relationship to level of resistance following exposure to cisplatin in cancer cells

One of the major complications in cancer chemotherapy with cisplatin as one of the important medicines in treatment regimens of different cancers is the development of resistance. One of the most described cellular defense mechanisms involved in resistance is glutathione [GSH], thus in this study, the effects of cisplatin on the total intracellular GSH level [GSHi] in some sensitive and resistant variants of human cell lines [hepatocarcinoma HepG2, sking A375, cisplatin sensitive glioblastoma U373MG and cisplatin resistant glioblastoma U373MGCP, cisplatin sensitive ovary A2780S and cisplatin resistant A2780CP cells] were studied. MTT assay was performed to measure cytotoxicity of cisplatin [33.3 microM for 1 hour]. Following cisplatin exposure, GSHi [per million cells] was evaluated using a photometrical assay up to 90 minutes. Our results indicate that there are significant differences between GSHi content of A2780CP and U373MGCP cells compared to other cell lines. Moreover, IC[50] of cisplatin in different cells seems to have a relation with mean of GSH level in 90 minutes [GSH [mean][90]]. As a conclusion, it seems that resistance to cisplatin in different cell lines is more related with the diverse patterns of GSHi variations following cisplatin exposure than its original level, and/or its cellular increase or decrease. It is also suggested that GSH [mean][90] may be used as a factor for the prediction of cellular resistance to cisplatin

Effect of curcumin on doxorubicin-induced cytotoxicity in H9c2 cardiomyoblast cells

Doxorubicin [DOX], a widely used chemotherapeutic agent can give rise to serve cardiotoxicity by inducing apoptosis. Curcumin, the active compound of the rhizome of Curcuma longa L. has anti-inflammatory, antioxidant and anti-proliferative activities. Curcumin has been identified to increase cytotoxicity in several cancer cell lines in combination with DOX, but there is no study about its effect and DOX on normal cardiac cells. Therefore, in the present study, we evaluated the effect of curcumin on apoptosis induced by DOX in H9c2 rat heart-derived cells. Cell viability was determined by MTT assay. Also, activation of caspase-3 was evaluated by spectrophotometry. Quantitative real time RT-PCR was used to evaluate the expression of c-IAP1. Detection of intracellular DOX accumulation was performed by flow cytometry. No toxicity observed when the cells exposed for 1 hr to different concentrations of curcumin, but pretreatment of cells with curcumin increased cytotoxicity of DOX in a dose dependent manner. Analysis of caspase-3 activation showed that curcumin pretreatment increased caspase-3 activation. RT-PCR analysis clearly showed that curcumin significantly decreased mRNA gene expression of c-IAP1 compared to cells treated with DOX alone. Pretreatment of H9c2 cells with DOX and curcumin had no effect on the intracellular accumulation of DOX. Our observations indicated that subtoxic concentrations of curcumin sensitize H9c2 cells to DOX-induce apoptosis. These results suggest that the use of curcumin in combination with DOX in malignancy must be reevaluated

Acute and subacute toxicity of teucrium polium total extract in rats

Teucrium Polium L. [TP] is widely used in traditional medicine of many countries including Iran. There are various reports about pharmacological properties of TP such as calcium antagonist, anti- ulcer, anti - diabetic. There are a few reports about possible toxicological effects of this plant. In the present study we designed to evaluate the subchronic toxicity of Teucrium Polium total extract in rats. Sprague Dawley rats [40 males, 40 females] were divided into four dose groups [10 animals/dose/sex] and were gavaged daily with either 100, 300 or 600 mg/kg of the total extract for 44 days. Control group was received normal saline. Body weight and food consumption was monitored daily. After 45 days animal was sacrificed and hematological and biochemical parameters, as well as weight of left kidney and liver were measured. There was no significant difference in hematological parameters in both sexes as compared to their respective Controls. In biochemical parameters, a significant increase [p<0.05] was seen in both ALT and AST enzyme activities in female rats receiving 300 mg/kg TP. There was also a significant increase in liver weight of male rats receiving 600 mg/kg. No other significant changes in any other parameter were observed. Present data suggests that female rats are more sensitive to higher doses of TP and that liver could serve as a target organ toxicity of this extract