Anticancer activity of thymoquinone against breast cancer cells: Mechanisms of action and delivery approaches.

The rising incidence of breast cancer has been a significant source of concern in the medical community. Regarding the adverse effects and consequences of current treatments, cancers' health, and socio-economical aspects have become more complicated, leaving research aimed at improved or new treatments on top priority. Medicinal herbs contain multitarget compounds that can control cancer development and advancement. Owing to Nigella Sativa's elements, it can treat many disorders. Thymoquinone (TQ) is a natural chemical derived from the black seeds of Nigella sativa Linn proved to have anti-cancer and anti-inflammatory properties. TQ interferes in a broad spectrum of tumorigenic procedures and inhibits carcinogenesis, malignant development, invasion, migration, and angiogenesis owing to its multitargeting ability. It effectively facilitates miR-34a up-regulation, regulates the p53-dependent pathway, and suppresses Rac1 expression. TQ promotes apoptosis and controls the expression of pro- and anti-apoptotic genes. It has also been shown to diminish the phosphorylation of NF-B and IKK and decrease the metastasis and ERK1/2 and PI3K activity. We discuss TQ's cytotoxic effects for breast cancer treatment with a deep look at the relevant stimulatory or inhibitory signaling pathways. This review discusses the various forms of polymeric and non-polymeric nanocarriers (NC) and the encapsulation of TQ for increasing oral bioavailability and enhanced in vitro and in vivo efficacy of TQ-combined treatment with different chemotherapeutic agents against various breast cancer cell lines. This study can be useful to a broad scientific community, comprising pharmaceutical and biological scientists, as well as clinical investigators.

Anti-cancer & anti-metastasis properties of bioorganic-capped silver nanoparticles fabricated from Juniperus chinensis extract against lung cancer cells.

The current study evaluated the anti-cancer properties of bio-functionalized silver nanoparticles fabricated by Juniperus chinensis leaf extracts. The nanoparticles were characterized by scanning electron microscopy, transmission electron microscopy, UV-visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, dynamic light scattering, Zeta potential and X-ray spectroscopy. Further, this study elucidated the cellular and molecular mechanisms of nanoparticles for anti-proliferative and apoptotic effects on human lung cancer cells (A549) and compared them with commercial drug cisplatin. The size of the spherical nanoparticle was 12.96 nm with negative zeta potential. Up-regulation of caspase 3,9 and p53, Annexin V-FITC/PI, DAPI staining, and ROS production indicated the remarkable apoptotic effect of AgNPs compared to cisplatin. Moreover, down-regulation of MMP2/MMP9 scratch and matrigel assays revealed anti-metastatic properties of AgNPs. Cell cycle analysis and downregulation of cyclin D1 indicated cancer cell cessation in the G0/G1 phase. Overall, the results revealed that the green-synthetized AgNPs had anti-metastasis and anti-proliferation effects on lung cancer cells in comparison to cisplatin with lower side effects on the normal cell line.

Anti-proliferative effects of Ziziphus spina-christi and Phlomis russeliana leaf extracts on HEK293 and MCF-7 Cell Lines and Evaluation of Bax and Bcl-2 Genes Expression Level in MCF-7 Cells.

To investigate the effects of Phlomis russeliana and Ziziphus spina-christi leaf extracts on apoptosis in breast cancer MCF-7 cells. Cell lines were divided into a control group and the groups exposed to 0.001, 0.01, 0.1, 1, and 10 mg/ml of Ziziphus spina-christi and Phlomis russeliana leaf extracts. Cell viability was quantified by the MTT assay. The expression of Bax and Bcl-2 genes was evaluated by Real-time PCR analysis. Statistical analysis was performed using ANOVA. HEK293 cell viability significantly increased in the groups exposed to 0.001, 0.01, and 0.1 mg/ml of Z.christi leaf extract and decreased in the group exposed to 10 mg/ml of P.russeliana leaf extract. MCF-7 cells viability significantly decreased in the groups exposed to 0.001, 0.01, 0.1, 1 and 10 mg/ml of Z.christi leaf extract and increased in the groups exposed to 0.001 and 0.01 mg/ml of P.russeliana leaf extract. The exposure of MCF-7 cells to 1 and 10 mg/ml of P.russeliana leaf extract also led to a significant decrease in cell viability. The cytotoxic effect of Z.christi was higher than P.russeliana leaf extracts on MCF7 cells.  1 mg/ml of Z.christi leaf extracts also significantly increased the expression level of Bax and Bcl-2 genes in MCF7 cells. Bcl-2 gene expression significantly increased in the group exposed to 10 mg/ml of P.ruseliana leaf extract.Despite P.russeliana leaf extract, lower Z.christi leaf extract concentrations inhibited MCF-7 cells proliferation. Ziziphus spina-christi and phlomis russeliana leaf extracts mechanism of action has occurred through the Bax-independent apoptotic pathway on MCF-7 cells.

Ecofriendly Biomolecule-Capped Bifidobacterium bifidum-Manufactured Silver Nanoparticles and Efflux Pump Genes Expression Alteration in Klebsiella pneumoniae.

Background: Klebsiella pneumoniae is currently considered as an immediate threat to human health due to its various multidrug efflux pumps. Microbially synthesized silver nanoparticles (AgNPs) are an attractive and eco-friendly approach to prevent antibiotic resistance in bacteria. In the present study, we compared the inhibitory effect of both commercial and green AgNPs by Bifidobacterium bifidum on OxqAB efflux pump genes in ciprofloxacin-resistant strains of K. pneumoniae. Materials and Methods: AgNPs were characterized by ultraviolet-visible spectrophotometer, Fourier transform infrared spectroscopy, X-ray diffraction, zeta potential, transmission electron microscopy, and scanning electron microscopy. Antibiogram was used to identify resistant isolates and the effect of the biosynthesized AgNPs against OxqAB efflux pump strains was assessed by the minimum inhibitory concentration (MIC) method. The expression levels of oxqAB genes were evaluated using real-time polymerase chain reaction (PCR) followed by exposure to subMICs of the AgNPs. Results: PCR results showed that 25 strains had OxqAB efflux pump and the MIC method indicated that AgNPs had an inhibitory effect on all resistant strains with OxqAB efflux pump. The efficacy of the synthetic nanoparticles was assessed by comparing the antiefflux pump activity with commercial AgNPs. In ciprofloxacin-resistant isolates, the oxqAB genes expression levels reduced in the subMIC of both AgNPs, whereas biosynthesized AgNPs had greater bactericidal effects compared with the commercial AgNPs. Conclusions: Efflux pumps could be an attractive target for our biosynthesized AgNPs. The oxqAB genes expression levels reduced in subMIC of both AgNPs, whereas biosynthesized AgNPs had greater bactericidal effects than the commercial AgNPs.

Antibiofilm effect of green engineered silver nanoparticles fabricated from Artemisia scoporia extract on the expression of icaA and icaR genes against multidrug-resistant Staphylococcus aureus.

Silver nanoparticles (AgNPs) are at the forefront of the swiftly developing scope of nanotechnology. In the current study, we investigated the green synthesis of AgNPs using Artemisia scoporia as a reducing and capping agent. The biosynthesized AgNPs were characterized using ultraviolet-visible spectroscopy, X-ray diffraction, Fourier-Transform infrared spectroscopy, dispersive absorption spectroscopy, scanning electron microscopy, and transmission electron microscopy. The efficacy of the nanoparticle synthesis was assessed by comparing the antibiofilm activity with commercial AgNPs. The effect of sub-minimum inhibitory concentrations (MICs) of AgNPs on biofilm formation was determined by microtiter plate assay. The expression level of the icaA and icaR genes was assessed by real-time polymerase chain reaction assay. The structural and functional aspects of AgNPs were confirmed. The expression levels of icaA and icaR in the isolates exposed to sub-MIC of both commercial and biosynthetic AgNPs were lower and higher than in the control group, respectively. Our results also indicated that greater reduction and induction in icaA and icaR gene expression were noticed with the sub-MIC doses of biosynthetic AgNP versus commercial AgNP, respectively. This study suggested the application of AgNPs as a significant therapeutic and clinical option in the future and usage for fabricating medical implants. Nevertheless, further investigation is required for examining the pharmaceutical and medicinal properties of AgNPs.