Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM.
At the molecular level, several developmental signaling pathways, such as Wnt/ß-catenin, have been associated with the initiation and subsequent progression of prostate carcinomas. The present report elucidated the anti-cancerous attributes of an anthraquinone, aloe-emodin (AE), against androgen-independent human prostate cancer DU145 cells. The cytotoxicity profiling of AE showed that it exerted significant cytotoxic effects and increased lactose dehydrogenase levels in DU145 cells (p < 0.01 and p < 0.001). AE also induced considerable reactive oxygen species (ROS)-mediated oxidative stress, which escalated at higher AE concentrations of 20 and 25 µM. AE also efficiently instigated nuclear fragmentation and condensation concomitantly, followed by the activation of caspase-3 and -9 within DU145 cells. AE further reduced the viability of mitochondria with increased cytosolic cytochrome-c levels (p < 0.01 and p < 0.001) in DU145 cells. Importantly, AE exposure was also correlated with reduced Wnt2 and ß-catenin mRNA levels along with their target genes, including cyclin D1 and c-myc. Furthermore, the molecular mechanism of AE was evaluated by performing molecular docking studies with Wnt2 and ß-catenin. Evidently, AE exhibited good binding energy scores toward Wnt2 and ß-catenin comparable with their respective standards, CCT036477 (Wnt2 inhibitor) and FH535 (ß-catenin inhibitor). Thus, it may be considered that AE was competent in exerting anti-growth effects against DU145 androgen-independent prostate cancer cells plausibly by modulating the expression of Wnt/ß-catenin signaling.
Breast cancer represents the most frequently occurring cancer globally among women. As per the recent report of the World Health Organization (WHO), it was documented that by the end of the year 2020, approximately 7.8 million females were positively diagnosed with breast cancer and in 2020 alone, 685,000 casualties were documented due to breast cancer. The use of standard chemotherapeutics includes the frontline treatment option for patients; however, the concomitant side effects represent a major obstacle for their usage. Carbazole alkaloids are one such group of naturally-occurring bioactive compounds belonging to the Rutaceae family. Among the various carbazole alkaloids, 3-Methoxy carbazole or C13H11NO (MHC) is obtained from Clausena heptaphylla as well as from Clausena indica. In this study, MHC was investigated for its anti-breast cancer activity based on molecular interactions with specific proteins related to breast cancer, where the MHC had predicted binding affinities for NF-κB with −8.3 kcal/mol. Furthermore, to evaluate the biological activity of MHC, we studied its in vitro cytotoxic effects on MCF-7 cells. This alkaloid showed significant inhibitory effects and induced apoptosis, as evidenced by enhanced caspase activities and the cellular generation of ROS. It was observed that a treatment with MHC inhibited the gene expression of NF-kB in MCF-7 breast cancer cells. These results suggest that MHC could be a promising medical plant for breast cancer treatment. Further studies are needed to understand the molecular mechanisms behind the anticancer action of MHC.
Inflammatory breast cancer (IBC) is one of the most belligerent types of breast cancer. While various modalities exist in managing/treating IBC, drug delivery using microneedles (MNs) is considered to be the most innovative method of localized delivery of anti-cancer agents. Localized drug delivery helps to treat IBC could limit their adverse reactions. MNs are nothing but small needle like structures that cause little or no pain at the site of administration for drug delivery via layers of the skin. The polyethylene glycol diacrylate (PEGDA) based MNs were fabricated by using three dimensional (3D) technology called Projection Micro-Stereo Lithography (PµSL). The fabricated microneedle patches (MNPs) were characterized and coated with a coating formulation comprising of gemcitabine and sodium carboxymethyl cellulose by a novel and inventive screen plate method. The drug coated MNPs were characterized by various instrumental methods of analysis and release profile studies were carried out using Franz diffusion cell. Coat-and-poke strategy was employed in administering the drug coated MNPs. Overall, the methods employed in the present study not only help in obtaining MNPs with accurate dimensions but also help in obtaining uniformly drug coated MNPs of gemcitabine for treatment of IBC. Most importantly, 100% drug release was achieved within the first one hour only.
Worldwide, the primary problem today is the proliferation of cancer and secondary bacterial infections caused by biofilms, as they are the principal causes of death due to the lack of effective drugs. A great deal of biological activities of silver nanoparticles (AgNPs) have made them a brilliant choice for the development of new drugs in recent years. The present study was conducted to evaluate the anticancer, antibacterial, anti-QS, and antibiofilm effects of AgNPs synthesized from Eruca sativa (E. sativa) leaf extract. The ultraviolet-visible (UV-Vis) spectra showed a peak of surface plasmon resonance at 424 nm λmax, which corresponded to AgNP formation. The Fourier transform infrared spectroscopy (FT-IR) confirmed that biological moieties are involved for the development of AgNPs. Moreover, transmission electron microscopy (TEM) analyses confirmed the spherical shape and uniform size (8.11 to 15 nm) of the AgNPs. In human lung cancer cells (A549), the anticancer potential of AgNPs was examined by the MTT [3-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay, scratch assay, and invasion assay. The results indicated that AgNPs inhibit the migration of A549 cells. The synthesized AgNPs showed MIC values of 12.5 µg/mL against Chromobacterium violaceum (C. violaceum) and 25 µg/mL against Pseudomonas aeruginosa (P. aeruginosa), which demonstrated their antibacterial abilities. Biological compounds that disable the QS system are being investigated as potential strategies for preventing bacterial infections. Thus, we analyzed the potential effectiveness of synthesized AgNPs in inhibiting QS-regulated virulence factors and biofilm formation in both strains of bacteria. In C. violaceum, the synthesized AgNPs significantly inhibited both violacein (85.18% at 1/2 × MIC) and acyl homoserine lactone (78.76% at 1/2 × MIC). QS inhibitory activity was also demonstrated in P. aeruginosa at a sub-MIC concentration (1/2 × MIC) by a reduction in pyocyanin activity (68.83%), total protease (68.50%), LasA activity (63.91%), and LasB activity (56.40%). Additionally, the exopolysaccharide production was significantly reduced in both C. violaceum (65.79% at 1/2 × MIC) and P. aeruginosa (57.65% at 1/2 × MIC). The formation of biofilm was also significantly inhibited at 1/2 × MIC in C. violaceum (76.49%) and in P. aeruginosa (65.31%). Moreover, a GC-MS analysis confirmed the presence of different classes of bioactive phytochemical constituents present in the leaf extract of E. sativa. On the basis of our results, we conclude that biologically synthesized AgNPs showed numerous multifunctional properties and have the potential to be used against human cancer and bacterial biofilm-related infections.
Bacterial cells have the ability to form biofilm onto the surfaces of food matrixes and on food processing equipment, leading to a source of food contamination posing serious health implications. Therefore, our study aimed to determine the effect of Eruca sativa Miller (E. sativa) crude extract against biofilms of food-borne bacteria along with in silico approaches to investigate adhesion proteins responsible for biofilm activity against the identified phytochemicals. The antibacterial potential of crude extract was evaluated using agar well diffusion technique and combinations of light and scanning electron microscopy to assess the efficacy of crude extract against the developed biofilms. Our results showed that crude extract of E. sativa was active against all tested food-borne bacteria, exhibiting a rapid kinetics of killing bacteria in a time-dependent manner. MIC and MBC values of E. sativa crude extract were found to be ranging from 125 to 500 µg/mL and 250 to 1000 µg/mL respectively. Furthermore, inhibition of developed biofilm by E sativa was found to be ranging from 58.68% to 73.45% for all the tested strains. The crude extract also reduced the viability of bacterial cells within biofilms and amount of EPS (ranging 59.73-82.77%) in the biofilm matrix. Additionally, the microscopic images also revealed significant disruption in the structure of biofilms. A molecular docking analysis of E. sativa phytochemicals showed interaction with active site of adhesion proteins Sortase A, EspA, OprD, and type IV b pilin of S. aureus, E. coli, P. aeruginosa, and S. enterica ser. typhi, respectively. Thus, our findings represent the first demonstration of E. sativa crude extract's bioactivity and potency against food-borne bacteria in their planktonic forms, as well as against the developed biofilms. Therefore, a possible mechanistic approach for inhibition of biofilm via targeting adhesion proteins can be explored further to target biofilm producing food-borne bacterial pathogens.
