Anticancer and Antimicrobial Activity of Red Sea Seaweeds Extracts-Mediated Gold Nanoparticles

Biosynthesis of gold nanoparticles (AuNPs) is emerging as a better alternative to traditional chemical-based techniques. During this study, extracts of different marine algae species Ulva rigida (green algae), Cystoseira myrica (brown Algae), and Gracilaria foliifera (red Algae) were utilized as reducing and capping agents to synthesize AuNPs. AuNPs capped by U. rigida, C. myrica, and G. foliifera were confirmed by the appearance of surface plasmonic bands at 528, 540, and 543 nm, respectively. Transmission electron microscopy revealed mostly spherical shapes of AuNPs having a size of about 9 nm, 11 nm, and 13 nm for C. myrica, and G. foliifera extracts, respectively. Fourier transform-infrared spectroscopy (FTIR) illustrated the major chemical constituents of U. rigida, C. myrica, and G. foliifera. LC50 values of the biosynthesized AuNPs against Artemia salina nauplii were calculated at a range of concentrations (5-188 μg ml−1) after 16 to 24h. AuNPs concentration-dependent lethality was noted and U. rigida extracts-mediated AuNPs presented the lowest cytotoxicity. The biosynthesized AuNPs exhibited significant anticancer activity (86.83%) against MCF-7 cell lines (human breast adenocarcinoma cell lines) at 188 µg/ml concentration. G. foliifera demonstrated the highest anticancer value (92.13%) followed by C. myrica (89.82%), and U. rigida (86.83%), respectively. The AuNPs synthesized by different algal extracts showed variable antimicrobial activity against the tested pathogenic microorganisms. AuNPs of U. rigida extracts showed significant antimicrobial activity against dermatophytic fungi Trichosporon cataneum (30 mm) followed by Trichophyton mantigrophytes (25 mm). Furthermore, it also exhibited mild activity against Escherichia coli (17 mm), Cryptococcus neoformans (15 mm), Candida albicans (13 mm), and Staphylococcus aureus (11mm), respectively whereas no effects were observed against Bacillus cereus. To conclude, AuNPs can be effectively synthesized by marine algal species, and particularly U. rigida extracts could be effective reducing agents for the green AuNPs synthesis. These AuNPs could potentially serve as efficient alternative anticancer agents against human breast adenocarcinoma and anti-dermatophytes associated with skin infections.

Annihilating efficacy of Euphorbia hirta L. extracts on Artemia salina Nauplii and human breast adenocarcinoma cells (MCF-7 & MDA-MB-231)

Cancer is one of the major causes of death both in developed and developing countries. Recently the secondary metabolites produced by plants are being investigated due to their promising anticancer activities. Accordingly in the present study the anti-cancer potentials of Euphorbia hirta L., a well-known medicinal plant was explored for its anticancer activity. The methanol and aqueous extracts of Euphorbia hirta L. (EHA and EHM) were tested against Artemia salina nauplii for toxicity and MDA-MB-231 and MCF-7 human breast adenocarcinoma cell lines for its cytotoxic potentials. Both the extracts EHA and EHM exhibited maximum toxicity towards Artemia salina among which the methanol extract was able to kill all the nauplii in its highest concentration. Excitingly, Euphorbia hirta L. extracts exhibited minimal cytotoxicity on normal cells (VERO) than in human breast cancer cells (MDA-MB-231 and MCF-7). In conclusion, the results suggest that EHM extract of the selected plant may have promising therapeutic potential against human breast cancers and may lead to the development of new clinical drug specifically against ER-positive breast cancer.

Cytotoxicity evaluation of indomethacin-loaded polymeric nanoparticles in a human breast adenocarcinoma cell model/ Avaliação da citotoxicicidade de nanopartículas poliméricas contendo indometacina em modelo celular de adenocarcinoma de mama humano

Novas pesquisas indicam que anti-inflamatórios podem ser aplicados como agentes anti-cancerígenos como indometacina para hepatocarcinoma humano, canceres de colon e estômago. Como sabe-se, indometacina possui efeitos adversos gastrointestinais, cardiovasculares e renais. Uma vez que cancer de mama tem alta incidência e não há estudo da indometacina carreada em nanopartículas para esta aplicação, este estudo envolve o desenvolvimento de nanocapsulas de poli-epsilon-caprolactona carregadas com indometacina para a redução de citotoxicidade como agente quimioprotetor para cancer de mama. O nanocarreador foi preparado por método de deposição interfacial e sua caracterização foi realizada por determinação de pH, diâmetro médio e índice de polidispersão por espalhamento dinâmico de luz, potencial zeta por mobilidade eletroforética, eficiência de encapsulação por método de cromatografia líquida de alta eficiência e seu ensaio de citotoxicidade com linhagem de células queratinócitos (HaCaT) e células de cancer de mama (MCF-7). As formulações branca (C-NC) e contendo indometacina (Ind-OH-NC) mostraram leve pH ácido, diâmetros em torno de 200 nm e PDI0,2 com potencial zeta em torno de -20 mV e eficiência de encapsulação de 99% (1 mg.mL-1), cujo coeficiente de distribuição indicou efeito de permeação e retenção (efeito EPR). Ambas formulações não foram citotóxicas às células HaCaT, provando serem seguras às células normais e Ind-OH-NC teve uma permeação concentração e tempo-dependente e teve eficácia em reduzir a viabilidade celular da linhagem MCF-7.

Calophyllum brasiliense Extracts Induced Apoptosis in Human Breast Adenocarcinoma Cells

Aims: Apoptosis, or programmed cell death, is linked to several mechanisms of cell growth control. The present work aimed at evaluating the induction of apoptosis in MCF-7 human breast adenocarcinoma cell by Calophyllum brasiliense. Study design: The tests were performed in triplicates in the apoptosis assays and sextuplicates in the cytotoxic assays, to each group, and the data expressed the mean +/- standard deviations. The cytotoxicity IC50s were obtained based on nonlinear regression curve fit. Two-way ANOVA and Tukey’s tests were applied in the apoptosis analyses. Place and duration of study: The work was done at the Center for Research in Biodiversity (Cell Culture Laboratory, and Phytochemistry Laboratory), and Research Center (Molecular Biology Laboratory), Paulista University, between Jan 2019 and Dec 2019. Methodology: Two aqueous extracts, obtained from the stem (STE) and from the leaves (LFE) of Calophyllum brasiliense by a 24-h maceration, were submitted to a cytotoxic assay against MCF-7 breast cancer cell lines at the concentrations of 0.01 µg/ml, 0.1 µg/ml, 1.0 µg/ml, 10 µg/ml and 100 µg/ml. They were also subjected to the evaluation of apoptosis and necrosis cell death induction at concentrations of 50, 100 and 200 μg/ml, after 6 h, 12 h and 24 h. Curcumin was used as a reference drug for both cytotoxic (50 mM, 5.0 mM, 0.5 mM, 0.05 mM and 0.005 mM ) and apoptosis/necrosis (12.5 μM, 25 μM and 50 μM / 6 h, 12 h and 24 h) assays. Apoptosis and necrosis were accessed by the use of annexin V and 7-AAD, in a two-channel flow cytometer. Results: In terms of the cytotoxic activity, STE (IC50 7.86 µg/ml) was more toxic than LFE (IC50 74.35 µg/ml), and curcumin IC50 was 0.00159 µg/ml. STE induced 21.19 % and LFE, 20.63 %, in comparison to 13.4% of apoptosis induction by curcumin. The results of apoptosis induction in the cancer cells were achieved at 24 h, extract concentrations at 100 µg/ml. Conclusion: Both the extracts, STE and LFE, were cytotoxic against MCF-7 breast cancer cell line, and induced more apoptosis in MCF-7 cells than curcumin, suggesting that they are high potential sources of natural product-inducing apoptosis agents to be used against adenocarcinoma breast cells.

Anti-cancer Effects of Epigenetics Drugs Scriptaid and Zebularine in Human Breast Adenocarcinoma Cells

Background: High relapse and metastasis progression in breast cancer patients have prompted the need to explore alternative treatments. Epigenetic therapy has emerged as an attractive therapeutic strategy due to the reversibility of epigenome structures. Objective: This study investigated the anti-cancer effects of epigenetic drugs scriptaid and zebularine in human breast adenocarcinoma MDA-MB-231 and MCF-7 cells. Methods: First, the half maximal inhibitory concentration (IC50) of scriptaid, zebularine and the combination of both drugs on human breast adenocarcinoma MDA-MB-231 cells was determined. Next, MDA-MB-231 and MCF-7 cells were treated with scriptaid, zebularine and the combination of both. After treatments, the anti-cancer effects were evaluated via cell migration assay, cell cycle analysis and apoptotic studies, which included histochemical staining and reverse-transcriptase polymerase chain reaction (RT-PCR) of the apoptotic genes. Results: Both epigenetic drugs inhibited cell viability in a dose-dependent manner with 2 nM scriptaid, 8 µM zebularine and combination of 2 nM scriptaid and 2 µM zebularine. Both MDA-MB-231 and MCF-7 cells exhibited a reduction in cell migration after the treatments. In particular, MDA-MB-231 cells exhibited a significant reduction in cell migration (p < 0.05) after the treatments of zebularine and the combination of scriptaid and zebularine. Besides, cell cycle analysis demonstrated that scriptaid and the combination of both drugs could induce cell cycle arrest at the G0/G1 phase in both MDA-MB-231 and MCF-7 cells. Furthermore, histochemical staining allowed the observation of apoptotic features, such as nuclear chromatin condensation, cell shrinkage, membrane blebbing, nuclear chromatin fragmentation and cytoplasmic extension, in both MDA-MB-231 and MCF-7 cells after the treatments. Further apoptotic studies revealed that the upregulation of pro-apoptotic Bax, downregulation of anti-apoptotic Bcl-2 and elevation of Bax/Bcl-2 ratio were found in MDA-MB-231 cells treated with zebularine and MCF-7 cells treated with all drug regimens. Conclusion: Collectively, these findings suggest that scriptaid and zebularine are potential anti-cancer drugs, either single or in combination, for the therapy of breast cancer. Further investigations of the gene regulatory pathways directed by scriptaid and zebularine are definitely warranted in the future.

Vepris macrophylla Essential Oil Produces Notable Antiproliferative Activity and Morphological Alterations in Human Breast Adenocarcinoma Cells

Medicinal plants contain numerous bioactive molecules that synergistically provide therapeutic benefits. We have devoted our attention to various EOs without toxicity to normal cells, studying their activities against human cancer cells. In particular, we have studied the cytotoxicity of Vepris macrophylla (Baker) I. Verd. EO. V. macrophylla is an evergreen tree of Madagascar where is much appreciated as a source of traditional remedies. Its major volatile components are citral, i.e., a mixture of neral and geranial, citronellol and myrcene. The antiproliferative activities of V. macrophylla EO were studied against human breast adenocarcinoma cell line SKBR3. Cellular metabolism was analyzed by MTT assay at different concentrations of EO and at different times of incubation (24, 48 and 72 h). Moreover, morphological and ultrastructural analyses were performed to study its antiproliferative effects against human adenocarcinoma cells, demonstrating the ability of V. macrophylla EO, stored inside numerous intracellular vesicles, to damage both plasma membranes and disorganize the cytoskeleton protein as actin filaments.

Cancer selective cytotoxicity of Sida acuta extracts on Artemia salina and human breast adenocarcinoma cells

Cancer is one of the major causes of morbidity and mortality globally. The interests in the use of plants or plant-derived compounds are increasing recently due to their promising results in chemoprevention. The present study investigates the anti-cancer potentials of Sida acuta, a traditionally well-known medicinal plant. Accordingly, the methanol and aqueous extracts of S. acuta (SAM and SAA) were tested against Artemia salina nauplii for toxicity and on MDA-MB-231 and MCF-7 human breast adenocarcinoma cell lines for cytotoxic and apoptotic properties. Both the extracts, SAM and SAA exhibited higher toxicity towards Artemia salina. Interestingly, the extracts exhibited minimal cytotoxicity in normal cells (VERO) than in human breast cancer cells (MDA-MB-231 and MCF-7). The highly active SAA successfully induced apoptosis in MDA MB 231 and MCF-7 cells showing 17.81% and 4.27% of late apoptotic cells and 27.14% and 37.32% of early apoptotic cells, respectively. Most of the drugs being developed from plant sources had landed successfully in clinical trials. In conclusion, the observations clearly suggest that SAA may have possible therapeutic potential against human breast cancer-derived diseases specifically against ER-positive breast cancer.

Trichostatin A and Zebularine along with E-cadherin re-expression enhance tumour necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated cell cycle arrest in human breast adenocarcinoma cells

Breast cancer is the leading cause of death among women in which its definite cure remains uncovered. Tumour necrosis factor-related apoptosis inducing ligand (TRAIL) is a potential anti-cancer agent due to its selective killing towards cancer cells while sparing the healthy cells. However, it is limited by the development of TRAIL resistance. With the attempt to overcome TRAIL resistance, this research embarked to study the effect of epigenetic drugs, Trichostatin A (TSA) and Zebularine (Zeb) along with E-cadherin re-expression on anti-cancer effect in human breast adenocarcinoma cells. The MDA-MB-231 re-expressed with E-cadherin (231-EGFP) was treated with TSA and Zeb before being treated with TRAIL (TZT) to compare the effect on MDA-MB-231 and MCF-7. The cell viability, cell cycle and migration assays were conducted on these cells, prior to reverse-transcription-polymerase chain reaction (RT-PCR) targeted on proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 2 (CDK2), matrix metalloproteinase 9 (MMP9). TZT induced a significant increase in G0/G1-arrested cell population and reduction in cell viability in 231-EGFP. These were verified by the suppression of PCNA and CDK2 mRNA expression. However, there was a negligible effect to reduce the cell migration of the invasive MDA-MB-231 and 231-EGFP cells in accordance with the lack of down-regulation of MMP9. In conclusion, this research shows that TSA and Zeb have sensitized breast cancer towards TRAIL treatment in 231-EGFP cells, validating the potentiality of E-cadherin as a biomarker of TRAIL treatment efficacy in the invasive breast cancer.