In vitro evaluation of the antitumor effect of bismuth lipophilic nanoparticles (BisBAL NPs) on breast cancer cells

Aim: The objective of this study was to evaluate the antitumor activity of lipophilic bismuth nanoparticles (BisBAL NPs) on breast cancer cells. Materials and methods: The effect of varying concentrations of BisBAL NPs was evaluated on human MCF-7 breast cancer cells and on MCF-10A fibrocystic mammary epitheliocytes as noncancer control cells. Cell viability was evaluated with the MTT assay, plasma membrane integrity was analyzed with the calcein AM assay, genotoxicity with the comet assay, and apoptosis with the Annexin V/7-AAD assay. Results: BisBAL NPs were spherical in shape (average diameter, 28 nm) and agglomerated into dense electronic clusters. BisBAL NP induced a dose-dependent growth inhibition. Most importantly, growth inhibition was higher for MCF-7 cells than for MCF-10A cells. At 1 µM BisBAL NP, MCF-7 growth inhibition was 51%, while it was 11% for MCF-10A; at 25 µM BisBAL NP, the growth inhibition was 81% for MCF-7 and 24% for MCF-10A. With respect to mechanisms of action, a 24-hour exposure of 10 and 100 µM BisBAL NP caused loss of cell membrane integrity and fragmentation of tumor cell DNA. BisBAL NPs at 10 µM were genotoxic to and caused apoptosis of breast cancer cells. Conclusion: BisBAL NP-induced growth inhibition is dose dependent, and breast cancer cells are more vulnerable than noncancer breast cells. The mechanism of action of BisBAL NPs may include loss of plasma membrane integrity and a genotoxic effect on the genomic DNA of breast cancer cells. Keywords: antitumor activity, bismuth nanoparticles, breast cancer, chemotherapy, cytotoxicit

Cumulative antitumor effect of bismuth lipophilic nanoparticles and cetylpyridinium chloride in inhibiting the growth of lung cancer

Objective: To determine the combined antitumor effect of bismuth lipophilic nanoparticles (BisBAL NP) and cetylpyridinium chloride (CPC) on human lung tumor cells. Material and methods: The human lung tumor cells A549 were exposed to 1–100 µM BisBAL NP or CPC, either separately or in a 1:1 combination. Cell viability was measured with the PrestoBlue assay, the LIVE/DEAD assay, and fluorescence microscopy. The integrity and morphology of cellular microtubules were analyzed by immunofluorescence. Results: A 24-h exposure to 1 µM solutions reduced A549 growth with 21.5% for BisBAL NP, 70.5% for CPC, and 92.4% for the combination ( p < 0.0001), while a 50 µM BisBAL NP/CPC mixture inhibited cell growth with 99% ( p < 0.0001). BisBAL NP-curcumin conjugates were internalized within 30 min of exposure and could be traced within the nucleus of tumor cells within 2 h. BisBAL NP, but not CPC, interfered with microtubule organization, thus interrupting cell replication, similar to the action mechanism of docetaxel. Conclusion: The growth inhibition of A549 human tumor cells by BisBAL NP and CPC was cumulative as of 1 µM. The BisBAL NP/CPC combination may constitute an innovative and cost-effective alternative for treating human lung cancer

Antimicrobial potential of AH Plus supplemented with bismuth lipophilic nanoparticles on E. faecalis isolated from clinical isolates

The objective of this study was to determine the antimicrobial potential of AH plus supplemented with bismuth lipophilic nanoparticles (BisBAL NPs) on the growth of Enterococcus faecalis isolated from patients with endodontic infections. BisBAL NPs, synthesized with the colloidal method, were characterized, in its pure form or AH Plus-absorbed, by energy-dispersive X-ray spectroscopy and scanning electron microscopy (EDS-SEM). Antimicrobial activity was evaluated with disc diffusion assays, and antibiofilm activity with fluorescence microscopy. BisBAL NP-supplemented AH Plus had a 4.9 times higher antimicrobial activity than AH Plus alone ( p = 0.0001). In contrast to AH Plus alone, AH Plus supplemented with BisBAL NP inhibited E. faecalis biofilm formation. The sealing properties of AH plus were not modified by the incorporation of BisBAL NPs, which was demonstrated by a 12-day split-chamber leakage assay with daily inoculation, which was used to evaluate the possible filtration of E. faecalis . Finally, BisBAL NP-supplemented AH plus-BisBAL NPs was not cytotoxic for cultured human gingival fibroblasts. Their viability was 83.7% to 89.9% after a 24-h exposure to AH Plus containing 50 and 10 µM BisBAL NP, respectively. In conclusion, BisBAL NP-supplemented AH Plus constitutes an innovative nanomaterial to prevent re-infection in endodontic patients without cytotoxic effects

Expresión de citocinas proinflamatorias, linfocitos T CD8+ y macrófagos inducida por MTA, Portland y Apexit

Tesis Univ. Granada. Departamento de Estomatología. Leída el 13 de mayo del 201

Cetylpyridinium chloride inhibits human breast tumor cells growth in a no-selective way

Objective: Analyze the antitumor capacity of cetylpyridinium chloride (CPC) on human breast tumor cells, and the possible action mechanism. Material and methods: The human breast tumor cells MCF-7 and no-tumor breast cells MCF-10A were exposed to CPC under various condition (concentration and duration). Cell viability was measured with MTT assay, the LIVE/DEAD assay, and fluorescence microscopy. Membrane permeability after CPC exposure was evaluated by Calcein AM assay, mitochondrial morphology with a MitoView staining, and genotoxicity with the comet assay and fluorescence microscopy. Results: CPC was cytotoxic to both MCF-7 and MCF-10A as of a 24-h exposure to 0.1 µM. Cytotoxicity was dose-dependent and reached 91% for MCF-7 and 78% for MCF-10A after a 24-h exposure to 100 µM CPC, which outperformed the positive control doxorubicin in effectiveness and selectivity. The LD50 of CPC on was 6 µM for MCF-7 and 8 µM for MCF-10A, yielding a selectivity index of 1.41. A time response analysis revealed 64% dead cells after only 5 min of exposure to 100 µM CPC. With respect to the action mechanisms, the comet assay did not reveal genome fragmentation. On the other hand, membrane damage was dose-dependent and may also affect mitochondrial morphology. Conclusion: Cetylpyridinium chloride inhibits MCF-7 cell growing in a non-selective way as of 5 min of exposure. The action mechanism of CPC on tumor cells involves cell membrane damage without change neither mitochondrial morphology nor genotoxicity

Comparative Study of Antitumor Activity between Lipophilic Bismuth Nanoparticles (BisBAL NPs) and Chlorhexidine on Human Squamous Cell Carcinoma

The objective of this study was to compare the antitumor activity of lipophilic bismuth nanoparticles (BisBAL NPs) and chlorhexidine (CHX) on human squamous cell carcinoma. BisBAL NPs were synthesized by colloidal method and characterized by energy dispersive X-ray spectroscopy in conjunction with scanning electron microscopy (EDS-SEM). The effect of BisBAL NPs and CHX on oral cancer cell line (CAL-27) and nontumor control cell human gingival fibroblasts (HGFs) was determined by MTT cell viability assay. The obtained results showed selective inhibition of CAL-27 cell growth by BisBAL nanoclusters. A 24 h exposition to 25 μM BisBAL NP decreased 91% of CAL-27 cell growth, while nontumor HGFs cells were unaffected by BisBAL NPs showing 90% of cell viability. In contrast, CHX kills both CAL-27 and HGFs with the same efficacy. 25 μM of CHX decreased 97% and 80% of tumor and nontumoral cell growth. BisBAL NP and CHX alter cell permeability suggesting that action mechanism may include loss of cell membrane integrity. Also, CHX and not BisBAL NP presented genotoxicity on genomic DNA of tumor cells. As conclusion, BisBAL NPs have a selective antitumor activity on human squamous cell carcinoma, unlike CHX which was cytotoxic for both tumoral and nontumoral control cells