The study draws attention to gold nanoparticles as a resource for technological innovation in the anti-inflammatory, analgesic and anti-tumor fields. GNPs have biological effects that deserve investigation to assess their full interaction with organic systems.
It has been well-characterized that the renin-angiotensin system (RAS) physiologically regulates systemic arterial pressure. However, RAS signaling has also been shown to increase cell proliferation during malignancy, and angiotensin receptor blockers (ARBs) are able to decrease pro-survival signaling by inhibiting anti-apoptotic molecules and suppressing caspase activity. In this study, the apoptotic effects of telmisartan, a type of ARB, was evaluated using a non-cancerous human renal cell line (HEK) and a human renal cell carcinoma (RCC) cell line (786). Both types of cells were treated with telmisartan for 4 h, 24 h, and 48 h, and then were assayed for levels of apoptosis, caspase-3, and Bcl-2 using MTT assays, flow cytometry, and immunostaining studies. Analysis of variance was used to identify significant differences between these data (P < 0.05). Following the treatment of 786 cells with 100 µM and 200 µM telmisartan, a marked inhibition of cell proliferation was observed. 50 µM cisplatin also caused high inhibition of these cells. Moreover, these inhibitions were both concentration- and time-dependent (P < 0.05). Various apoptotic effects were also observed compared with control cells at the 24 h and 48 h timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were detected, consistent with induction of cell death. In contrast, treatment of HEK cells with telmisartan did not produce an apoptotic effect compared with control cells at the 24 h timepoint (P > 0.05). Treatment with cisplatin promoted in HEK cells high index of apoptosis (P < 0.001). Taken together, these results suggest that telmisartan induces apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human RCC cells.
The ability to induce apoptosis is an important marker for cytotoxic antitumor agents. Some natural compounds have been shown to modulate apoptosis pathways that are frequently blocked in human cancers, and therefore, these compounds provide novel opportunities for cancer drug development. Phyllanthus, a plant genus of the family Euphorbiaceae, exhibits multiple pharmacological actions. Of these, Phyllanthus niruri extracts exhibit significant antitumor activity, which is consistent with the traditional medicinal use of this plant. To examine the apoptotic effects of a spray-dried extract of P. niruri (SDEPN), human hepatocellular carcinoma cells (HepG2, Huh-7), colorectal carcinoma cells (Ht29) and keratinocytes (HaCaT) were exposed to the extract for 4, 8 and 24 h. Flow cytometry and caspase-3 immunostaining were used to detect apoptosis, while analysis of variance was applied to identify significant differences between groups (P < 0.05). At all timepoints, the SDEPN induced significantly different cytotoxic effects for HepG2 and Huh-7 cells compared with control cells (P < 0.001). In contrast, the SDEPN had a protective effect on HaCaT cells compared with control cells at all timepoints (P < 0.001). In caspase-3 assays, activation was detected after cell death was induced in Huh-7 and HepG2 cancer cells by the SDEPN. In combination, these results indicate that the SDEPN is selectively toxic towards cancer cell lines, yet is protective towards normal cells.
In this study we show, for the first time, that gold nanoparticles (AuNPs) synthesized by a simple, inexpensive, and environmentally-correct method can be easily conjugated with the antibodies anti--catenin and anti-E-cadherin to specifically target colorectal carcinoma cells. The antibody/AuNPs conjugates were then successfully applied for imaging cancerous cells with fluorescence confocal microscopy. The AuNPs as well as the conjugates were very stable in high-salinity medium, a prerequisite for application in physiological-like environments. Fluorescence results suggest that conjugation was achieved by direct adsorption of antibodies on the AuNPs surface. Finally, compared with a standard method of cell staining, our method is less laborious and the preparation time (from immobilization of cells onto glass cover slips until observation by confocal microscopy) decreased from 27 h to about 1 h, which makes the method eligible for colorectal cancer diagnostic.
Maytenus is the largest genus of the family Celastraceae and the species Maytenus ilicifolia (popularly known as 'Espinheira Santa'). It is widely used in traditional Brazilian medicine to treat stomach conditions including nausea, gastritis, and ulcers. In this study, the apoptotic effects of a spray-dried extract of M. ilicifolia (SDEMI) was evaluated using human hepatocellular cells (HepG2), colorectal carcinoma cells (HT-29), and normal keratinocytes (HaCaT). Cells were treated with SDEMI for 4 and 24 h, then were assayed for levels of apoptosis, caspase-3, and Bcl-2 by flow cytometry, immunostaining, and Western blot, respectively. Significant differences between groups were determined using analysis of variance (P < 0.05). For HepG2 and HT-29 cells treated with SDEMI, various cytotoxic effects were observed compared with control cells at all timepoints assayed (P < 0.001). Furthermore, positive caspase-3 staining and down-regulation of Bcl-2 were observed, consistent with the induction of cell death detected in these cell lines. In contrast, treatment of HaCaT cells with SDEMI was associated with a protective effect compared with control cells at both timepoints (P < 0.001). For example, increased expression of Bcl-2 and negative caspase-3 staining were detected. Taken together, these results suggest that SDEMI protects normal cells, while SDEMI mediates induction of apoptosis via down-regulation of Bcl-2 and involvement of caspase-3 in human carcinoma cells.
Excitation emission matrix (EEM) fluorescence spectroscopy combined with the OPLS method has been investigated as a promising tool to discriminate between normal and cancer cell lines in two datasets: (i) using several types of normal and cancer cells (including 3T3, ARPE, HEK, HepG2, HeLa, HT-29 and 786-0 cells); (ii) considering the expression of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9) in suspensions of HEK and 786-0 cell lines. Partial Least Squares-Discriminant Analysis (PLS-DA) using the score matrix from PARAFAC (Parallel Factor Analysis), UPLS-DA (Unfolded Partial Least Squares with Discriminant Analysis) and orthogonal projection to latent structures (OPLS) were used as the bases for the discrimination models. UPLS-DA presented relevant performance for cancer cells in both datasets, with 100% and 66.7% correct prediction for first and second cases, respectively, and poor discrimination relative to normal cells in the first dataset (25%). By using the OPLS, we achieved 75% correct prediction for normal cells and maintained 100% concordance for cancer objects. On applying OPLS to the second dataset, we obtained 100% correct prediction in both classes (normal and cancer) for calibration and prediction sets. These results suggest that EEM fluorescence spectroscopy combined with chemometrics could be used as a clinical tool for cancer cell detection based on intrinsic biomolecular signatures.
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