Targeted Photothermal Therapy of Melanoma in C57BL/6 Mice using Fe3O4@Au Core-shell Nanoparticles and Near-infrared Laser.

BACKGROUND: Gold nanoshells can be tuned to absorb a particular wavelength of light. As a result, these tunable nanoparticles (NPs) can efficiently absorb light and convert it to heat. This phenomenon can be used for cancer treatment known as photothermal therapy. In this study, we synthesized Fe3O4@Au core-shell NPs, magnetically targeted them towards tumor, and used them for photothermal therapy of cancer. OBJECTIVE: The main purpose of this research was to synthesize Fe3O4@Au core-shell NPs, magnetically target them towards tumor, and use them for photothermal therapy of cancer. MATERIAL AND METHODS: In this experimental study, twenty mice received 2 × 106 B16-F10 melanoma cells subcutaneously. After tumors volume reached 100 mm3, the mice were divided into five groups including a control group, NPs group, laser irradiation group, NPs + laser group and NPs + magnet + laser group. NPs were injected intravenously. After 6 hours, the tumor region was irradiated by laser (808 nm, 2.5 W/cm2, 6 minutes). The tumor volumes were measured every other day. RESULTS: The effective diameter of Fe3O4@Au NPs was approximately 37.8 nm. The average tumor volume in control group, NPs group, laser irradiation group, NPs + laser irradiation group and NPs + magnet + laser irradiation group increased to 47.3, 45.3, 32.8, 19.9 and 7.7 times, respectively in 2 weeks. No obvious change in the average body weight for different groups occurred. CONCLUSION: Results demonstrated that magnetically targeted nano-photothermal therapy of cancer described in this paper holds great promise for the selective destruction of tumors.

Atorvastatin enhances apoptotic effects of tamoxifen on melanoma cancer cells.

AIM: Tamoxifen engages mitochondrial estrogen receptor beta as an antagonist, increases mitochondrial cytotoxicity and induces tumor cell death. Tamoxifen also engages plasma membrane estrogen receptor alpha as an agonist, while it is suggested that in some users its activation is put into action by mechanism of resistance to tamoxifen. Apoptotic inducers have been shown to promote tamoxifen-induced cell death, which might be of great importance in overcoming tamoxifen resistance. Considering the pleiotropic effects of statins, in the present study, we investigated the effects of atorvastatin on tamoxifen-induced intrinsic apoptotic pathway activity in melanoma cells. METHODS: Melanoma B16F10 cells were treated for 24 and 48 h with various concentrations of tamoxifen, atorvastatin and combination of tamoxifen + atorvastatin. Cells with no treatment were considered a control group, and the study was then followed by quantitative RT- PCR assay. Bax and cytochrome c gene expressions were calculated by ΔΔct method. RESULTS: Co-treatment of atorvastatin + tamoxifen could strongly enhance the expression of pro/apoptotic factors of Bax and cytochrome c in melanoma cells compared to the tamoxifen and atorvastatin groups. CONCLUSION: In general, we conclude that the atorvastatin-induced increase in Bax and cytochrome c gene expression might be a permissive response to tamoxifen-induced cell death (Fig. 2, Ref. 37).

Antihypertensive and antioxidant effects of a hydroalcoholic extract obtained from aerial parts of Otostegia persica (Burm.) Boiss.

Otostegia persica (Burm.) Boiss. is used for the treatment of various diseases in traditional medicine. The aim of this study was to assess the effects of hydroalcoholic extract of the aerial parts of O. persica in dexamethasone (Dex) induced hypertension in male Wistar rats. For induction of hypertension, Dex at 30 µg/kg/day was administered subcutaneously for 14 days. In a prevention study, animals received O. persica extract orally at various doses of 100, 200 and 400 mg/kg 4 days before Dex administration and during the test period lasted for 18 days. In a reversal study, rats received O. persica extract from day 8 to 14. Systolic blood pressure (SBP) was measured using tail-cuff method. The weight of thymus gland was measured as a marker of glucocorticoid activity. The hydrogen peroxide (H2O2) concentration and ferric reducing antioxidant power (FRAP) were determined in plasma samples. Dex injection significantly increased SBP and plasma H2O2 levels while decreased the body and thymus weights and FRAP values. Oral administration of O. persica extract prevented and dose-dependently reversed a rise in SBP. Pre-treatment with O. persica extract also reduced the plasma H2O2 concentration, increased the plasma FRAP levels and prevented the body weight loss upon Dex administration. These results suggest antihypertensive and antioxidant effects of O. persica extract in Dex-induced hypertension. However, further investigations are needed to elucidate the detailed mechanism(s) of antihypertensive effect of this traditional herbal medicine.

Antiangiogenic and antiproliferative effects of black pomegranate peel extract on melanoma cell line.

In the present study possible effects of black pomegranate peel extract (PPE) on the B16F10 melanoma cells proliferation and Human Umbilical Vein Endothelial Cells (HUVECs) angiogenesis were investigated. PPE was added into the cell lines (B16F10 and HUVECs) media with different concentrations (10-450 µg/ml). After 48 h, the cell survival was measured by 3-(Dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide (MTT) assay. Angiogenesis was investigated by matrigel assay (PPE (200, 300, 400 µg/ml)); HUVECs, vascular endothelial growth factor (VEGF) mRNA expression was detected by quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) assay. VEGF concentration in culture medium of HUVECs was determined by enzyme-linked immunosorbent assay (ELISA). PPE had positive anti proliferative effect on melanoma cells in a dose-dependent manner, but not on HUVECs. The matrigel assay results indicated that PPE significantly inhibited length, size and junction of the tube like structures (P<0.05). VEGF mRNA expression and concentration levels in culture medium of PPE treated HUVECs reduced significantly in a concentration-dependent manner (P<0.05). Simultaneous inhibition of melanoma cell proliferation and angiogenesis proposed that, PPE can be a good candidate against melanoma development. Based on the results, PPE could effectively suppress angiogenesis potentially through a VEGF dependent mechanism. Further studies are needed to confirm these results.

Effect of human Wharton's jelly mesenchymal stem cell secretome on proliferation, apoptosis and drug resistance of lung cancer cells.

Multipotent mesenchymal stem cells (MSCs) are recently found to alter the tumor condition. However their exact role in tumor development is not yet fully unraveled. MSCs were established to perform many of their actions through paracrine effect. Thus investigation of MSC secretome interaction with tumor cells may provide important information for scientists who are attempting to apply stem cells in the treatment of the disease. In this study we investigated the effect of human Wharton's jelly derived MSC (WJ-MSCs) secretome on proliferation, apoptotic potential of A549 lung cancer cells, and their response to the chemotherapeutic agent doxorubicin. WJ-MSCs were isolated from human umbilical cord and then characterized according to the International Society for Cellular Therapy criteria and WJ-MSC secretome was collected. BrdU cell proliferation assay and Annexin V-PI staining were used for the evaluation of cytotoxic and proapoptotic effects of WJ-MSC secretome on A549 cells. WJ-MSC secretome neither induced proliferation of lung cancer cells nor affected the apoptotic potential of the tumor cells. We also studied the combinatorial effect of WJ-MSC secretome and the anticancer drug doxorubicinwhich showed no induction of drug resistance when A549 cells was treated with combination of WJ-MSC secretome and doxorubicin. Although MSCs did not show antitumor properties, our in vitro results showed that MSC secretome was not tumorigenic and also did not make lung cancer cells resistant to doxorubicin. Thus MSC secretome could be considered safe for other medical purposes such as cardiovascular, neurodegenerative, and autoimmune diseases which may exist or occur in cancer patients.

Antioxidant and cytoprotective effects of L-Serine on human endothelial cells.

Oxidative stress has been implicated as a prominent determinant in the development of several diseases such as atherosclerosis. Anti atherosclerotic effects of L-serine have been shown previously but its responsible mechanisms remained unidentified. This study aimed to investigate the antioxidant and cytoprotecrtive effects of L-serine and its possible mechanisms. For this purpose, cell viability analysis and nuclear factor-erythroid 2 (NF-E2)-related factor 2 (Nrf2) activity, heme oxygenase-1 (HO-1) concentration, total Nitric Oxide (NOx) production were evaluated in oxidative stress-induced Human Umbilical Vein Endothelial Cells (HUVECs) pretreated by L-serine. Cytoprotective effects of L-serine was measured through 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Nrf2 activity and HO-1 concentration were determined in the cell lysate by commercial immunoassay methods. NOx was assayed in the supernatant of culture medium through colorimetric Griess method. Pretreatment with L-serine (0.1-3.2 mM) protected endothelial cells from hydrogen peroxide-mediated cell cytotoxicity (H(2)O(2), 0.5 mM) and lead to significant induction of Nrf2 activity, HO-1 expresssion and NOx production. These findings demonstrated that L-serine has antioxidant and cytoprotective effects through the elevation of some crucial antioxidant factors such as Nrf2, HO-1 and NO.

Interleukin-10 and Transforming Growth Factor-ß in Early and Late Lesions of Patients with Leishmania major induced Cutaneous Leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. Better understanding of host immune response to the parasite leads to helpful strategies for disease control. Interleukin (IL)-10 and transforming growth factor (TGF)-ß are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. However, there is little information about the function of IL-10 and TGF-ß in old world cutaneous leismaniasis. The aim of this study was to analyze the role of IL-10 and TGF-ß in human cutaneous leishmaniasis due to Leishmania major infection. METHODS: Biopsies were obtained from lesions of twenty proven cases of L. major induced cutaneous leishmaniasis. IL-10 and TGF-ß positive cells were detected by immunofluorescence staining of frozen sections and compared between two groups of patients with early and late lesions. RESULTS: The mean percentage of IL-10 positive cells were significantly (P= 0.035) higher in late lesions (0.51±0.24) than early ones (0.15±0.07). Similar results were obtained for TGF-ß with mean percentages of 0.16±0.05 and 0.53±0.28 in early and late lesions respectively (P= 0.008). CONCLUSION: IL-10 and TGF-ß are present in lesions of L. major induced cutaneous leishmaniasis and contribute to the pathogenesis of long lasting disease forms.

Interleukin-10 and Transforming Growth Factor-ß in Early and Late Lesions of Patients with Leishmania major Induced Cutaneous Leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis is a neglected parasitic disease, which imposes massive human distress and financial costs to the endemic countries. Better understanding of host immune response to the parasite leads to helpful strategies for disease control. Interleukin (IL)-10 and transforming growth factor (TGF)-ß are important immune regulatory cytokines, which appear to develop non-healing forms of leishmaniasis. However, there is little information about the function of IL-10 and TGF-ß in old world cutaneous leismaniasis. The aim of this study was to analyze the role of IL-10 and TGF-ß in human cutaneous leishmaniasis due to Leishmania major infection. METHODS: Biopsies were obtained from lesions of twenty proven cases of L. major induced cutaneous leishmaniasis. IL-10 and TGF-ß positive cells were detected by immunofluorescence staining of frozen sections and compared between two groups of patients with early and late lesions. RESULTS: The mean percentage of IL-10 positive cells were significantly (P= 0.035) higher in late lesions (0.51±0.24) than early ones (0.15±0.07). Similar results were obtained for TGF-ß with mean percentages of 0.16±0.05 and 0.53±0.28 in early and late lesions respectively (P= 0.008). CONCLUSION: IL-10 and TGF-ß are present in lesions of L. major induced cutaneous leishmaniasis and contribute to the pathogenesis of long lasting disease forms.