Nanoformulated 3'-diindolylmethane modulates apoptosis, migration, and angiogenesis in breast cancer cells.

Background: It is well-established that specific herbal plants contain natural active ingredients that have demonstrated anti-cancer potential. Therefore, they are considered highly beneficial as a potential adjuvant, alternative or complementary agent in anti-cancer therapy. However, the low chemical stability and limited bioavailability of 3, 3'-Diindolylmethane (DIM), a plant-derived compound used in clinical settings, limit its therapeutic applications. To overcome this challenge, researchers have focused on developing innovative approaches to improve DIM's biological activity, such as utilizing nanoformulations. Here, we investigated the potential benefits of coating DIM nanoparticles (DIM-NPs) with PEG/chitosan in the treatment of breast cancer. Our results demonstrate the molecular mechanism underlying the activity of DIM-NPs, highlighting their potential as an effective therapeutic strategy for breast cancer treatment. Methods: DIM-PLGA-PEG/chitosan NPs were synthesised and characterised using dynamic light scattering (DLS) and evaluated the impact of these NPs on two breast cancer cell models. Results: DIM-NPs had an average diameter of 102.3 nm and a PDI of 0.182. When treated with DIM-NPs for 48 h, both MCF7 and MDA-MB-231 cells displayed cytotoxicity at a concentration of 6.25 g/mL compared to untreated cells. Furthermore, in MDA-MB-231 cells, treatment with 2.5 µg/mL of DIM-NPs resulted in a significant decrease in cell migration, propagation, and angiogenesis which was further enhanced at 10 µg/mL. In chicken embryos, treatment with 5 µg/mL of DIM-NPs on day 2 led to a significant reduction in angiogenesis. Furthermore, this treatment induced cell death through a regulatory pathway involving the upregulation of Bax and p53, as well as the downregulation of Bcl-2. These results were supported by in-silico analysis of DIM's binding affinity to key proteins involved in this pathway, namely Bax, Bcl-2, and p53. Conclusion: Our findings show that DIM-NPs induces apoptosis, inhibit migration, and reduce angiogenesis in breast cancer. However, further research using a preclinical cancer model may be necessary to determine the pharmacokinetics of DIM-NPs and ensure their safety and efficacy in vivo.

Novel curcumin nanoformulation induces apoptosis, and reduces migration and angiogenesis in liver cancer cells.

BACKGROUND: Curcumin has been used in the treatment of several diseases; however, its low pharmacologic profile reduces its therapeutic use. Towards improving its biological activity, nanoformulations have emerged. Thus, we aimed to determine whether curcumin nanoparticles (Cur-NPs) coated with PEG/chitosan improve the treatment of liver cancer (LC) cells and underpin the molecular mechanisms underlying their anti-cancer activity. METHODS: Cur-NPs were synthesised in the form of Cur-PLGA-PEG/chitosan NPs. The effect of Cur-NPs was assessed in HepG2 and Huh 7 LC cells and THLE-2 normal liver cells. RESULTS: The size of synthesised Cur-NPS was determined in the standard range of 141.2 ± 47.5 nm. Compared to THLE-2 cells, LC cells treated with Cur-NPs exerted cytotoxicity at 6.25 µg/mL after 48h. Treatment of HepG-2 cells with 2.5 µg/mL of Cur-NPs inhibited cell migration and this inhibition was augmented at 10 µg/mL (p < 0.001). Treatment of chicken embryo with 5 µg/mL Cur-NPs reduced angiogenesis (p < 0.001) of 4-day-old embryos. The nanoformulation upregulated Bax and p53 and downregulated Bcl-2 in a concentration-dependent manner and subsequently induce apoptosis in HepG-2 cells. CONCLUSION: Treatment of LC cells with Cur-NPs decreased cell proliferation, migration, and angiogenesis, and induced cell death by promoting the proapoptotic pathway.

Curcumin nanoparticles (Cur-NPs) increase the anticancer efficiency of Curcumin against liver cancer cells.Cur-NPs induce apoptotic cell death of Liver cancer cells.Cur-NPs have ant-angiogenesis and metastasis effect.

Synthesis, Solid State Structure, and Cytotoxic Activity of a Complex Dimer of Yttrium with Anthranilic Acid against Cancer Cells.

This paper presents the synthesis and isolation of a new binuclear complex of yttrium with anthranilic acid (HA). The complex [Y2(HA)6(H2O)4] Cl6.2C2H5OH (C1) was obtained as single crystals that its X-ray analysis revealed its triclinic P-1 space group in addition to anti-prismatic geometry around each of the yttrium ions. In the complex, the anthranilic acid ligands are bidentate, zwitter ionic and neutral, and the yttrium ions' charge is only compensated by six chloride ions. The cytotoxicity of this complex against human breast cancer MDA-MB-231 cells, prostate cancer PC-3 cells, and bladder cancer T-24 cells was evaluated. This yttrium complex displayed more cytotoxic activity against the bladder cancer cells with an IC50 value of 307.7 µg/ml (223 µM). On the other hand, the activities of complex C1 against the MDA-MB-231 and PC-3 cells were less significant respectively with IC50 values of 1097 µg/ml (796 µM) and 921 µg/ml (669 µM).

Synthesis, X-ray structure and anticancer activity evaluation of a binuclear La(III) complex with anthranilic acid.

A binuclear La(III) complex {[La2(HA)4(H2O)4(C2H5OH)2Cl2]Cl4 (C1)} with 2-aminobenzoic acid (HA) was prepared from the ligand and heptahydrated lanthanum chloride. The complex was characterised by X-ray crystallography that revealed anti-prismatic geometry around both of the lanthanum. In the complex, the four 2-aminobenzoic acid ligands are zwitter ionic and the two lanthanum(III) ions net charge is only counterbalanced by chloride ions. The complex cytotoxicity was determined against human breast (MDA-MB-231), prostate (PC-3) and bladder (T-24) cancer cells. This complex afforded cytotoxicity towards the T-24 bladder cancer cells with an IC50 value of 383.5 µg/mL (319 µM). In contrary, activities by the lanthanum complex with IC50 values of 1124 µg/mL (934 µM) and 739 µg/mL (614 µM) were, respectively, shown against the MDA-MB-231 and PC-3 cancer cells. This means the complex is more cytotoxic against the T-24 cells, despite that its activity is less compared with activities shown by classical drugs.

Saudi honey alleviates indomethacin-induced gastric ulcer via improving antioxidant and anti-inflammatory responses in male albino rats.

Recent years have reported a rise in the occurrence of gastric ulceration especially among young children and adults. This study investigated the mechanism by which two types of Saudi honey: Alnahal Aljawal honey (Wadi) or Bin Ghaithan honey (Talh) exerted their antiulcer potential in indomethacin-induced gastric ulceration. Four cohorts of rats were used: Group 1; Healthy controls, Group 2; Ulcerative animals, Group 3; Ulcerative + Wadi honey treatment, Group 4; Ulcerative + Talh honey treatment. We profiled the levels of different indicators of oxidative stress including the activities of gastric mucosal glutathione superoxide dismutase (SOD), catalase (CAT), peroxidase (GPx), reduced glutathione (GSH), and lipid peroxidation (measured as malondialdehyde; MDA). CRP content, IL-10, and plasma tumor necrosis factor-α were also evaluated. The stomach was visually examined for macroscopic lesions and using light microscope for histopathological changes in the glandular mucosa. Wadi or Talh honey significantly reduced the ulcer indices, and essentially protected the glandular mucosa from lesions. Wadi or Talh honey also significantly reduced the gastric mucosal concentrations of GPx, SOD and GSH. In addition, the administration of Wadi or Talh honey decreased gastric mucosal plasma TNF-α and MDA, CRP content, and IL-10 levels. In conclusion, Wadi or Talh honey possibly exerted their antiulcer potential via restoring the homeostasis and stabilizing the enzymatic (SOD and GPx) and non-enzymatic (GSH) antioxidants as well as reducing the levels of inflammatory cytokines (TNF-α, CRP content, IL-10 and, NF-κB activity), and inhibiting the lipid peroxidation in the gastric mucosa. Consequently, Wadi or Talh honey may be of beneficial therapy for patients diagnosed with gastric ulceration. Clinical studies need to be conducted to further support these findings.

Novel Pomegranate-Nanoparticles Ameliorate Cisplatin-Induced Nephrotoxicity and Improves Cisplatin Anti-Cancer Efficacy in Ehrlich Carcinoma Mice Model.

Cisplatin (CISP) is one of the most widely used anti-cancer chemotherapeutic agents with remarkable efficacy against various types of cancers. However, it has been associated with nephrotoxicity amongst other undesirable side effects. Pomegranate (PE) is a potent antioxidant and anti-inflammatory agent effective against cancer, with a superior benefit of not being associated with the common toxicities related to the use of conventional chemotherapeutic agents. However, the application of PE is limited by its reduced solubility and decreased bioavailability. We investigated the potential of a novel nanoparticle (NP) enclosing PE to enhance its solubility and improve its bioavailability, and efficacy to prevent CISP-associated nephrotoxicity in a mice model of Ehrlich solid carcinoma (ESC). All mice were grouped into four cohorts: (I) control, (II) tumor, (III) CISP, and (IV) CISP + PE-NPs. The data obtained demonstrated that PE-NPs was beneficial in potently ameliorating CISP-induced nephrotoxicity in ESC mice. PE-NPs significantly attenuated CISP-induced oxidative stress and lipid peroxidation in the kidney via improving activities of antioxidants (SOD, GSH, and CAT). Additionally, PE-NPs considerably decreased CISP-induced inflammation in the kidney by decreasing the levels of NF-kB, IL-1ß, and TNF-α. Notably, PE-NPs did not assuage the antitumor efficacy of CISP as revealed by histological assessment and tumor weight data. In summary, PE-NPs may be a potent alternative anticancer therapy devoid of nephrotoxicity.

Optimizing the catalytic activities of methanol and thermotolerant Kocuria flava lipases for biodiesel production from cooking oil wastes.

In this study, two highly thermotolerant and methanol-tolerant lipase-producing bacteria were isolated from cooking oil and they exhibited a high number of catalytic lipase activities recording 18.65 ± 0.68 U/mL and 13.14 ± 0.03 U/mL, respectively. Bacterial isolates were identified according to phenotypic and genotypic 16S rRNA characterization as Kocuria flava ASU5 (MT919305) and Bacillus circulans ASU11 (MT919306). Lipases produced from Kocuria flava ASU5 showed the highest methanol tolerance, recording 98.4% relative activity as well as exhibited high thermostability and alkaline stability. Under the optimum conditions obtained from 3D plots of response surface methodology design, the Kocuria flava ASU5 biocatalyst exhibited an 83.08% yield of biodiesel at optimized reaction variables of, 60 â—‹C, pH value 8 and 1:2 oil/alcohol molar ratios in the reaction mixture. As well as, the obtained results showed the interactions of temperature/methanol were significant effects, whereas this was not noted in the case of temperature/pH and pH/methanol interactions. The obtained amount of biodiesel from cooking oil was 83.08%, which was analyzed by a GC/Ms profile. The produced biodiesel was confirmed by Fourier-transform infrared spectroscopy (FTIR) approaches showing an absorption band at 1743 cm-1, which is recognized for its absorption in the carbonyl group (C=O) which is characteristic of ester absorption. The energy content generated from biodiesel synthesized was estimated as 12,628.5 kJ/mol. Consequently, Kocuria flava MT919305 may provide promising thermostable, methanol-tolerant lipases, which may improve the economic feasibility and biotechnology of enzyme biocatalysis in the synthesis of value-added green chemicals.

Enhancement of ß-Glucan Biological Activity Using a Modified Acid-Base Extraction Method from Saccharomyces cerevisiae.

Beta glucan (ß-glucan) has promising bioactive properties. Consequently, the use of ß-glucan as a food additive is favored with the dual-purpose potential of increasing the fiber content of food products and enhancing their health properties. Our aim was to evaluate the biological activity of ß-glucan (antimicrobial, antitoxic, immunostimulatory, and anticancer) extracted from Saccharomyces cerevisiae using a modified acid-base extraction method. The results demonstrated that a modified acid-base extraction method gives a higher biological efficacy of ß-glucan than in the water extraction method. Using 0.5 mg dry weight of acid-base extracted ß-glucan (AB extracted) not only succeeded in removing 100% of aflatoxins, but also had a promising antimicrobial activity against multidrug-resistant bacteria, fungi, and yeast, with minimum inhibitory concentrations (MIC) of 0.39 and 0.19 mg/mL in the case of resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, respectively. In addition, AB extract exhibited a positive immunomodulatory effect, mediated through the high induction of TNFα, IL-6, IFN-γ, and IL-2. Moreover, AB extract showed a greater anticancer effect against A549, MDA-MB-232, and HepG-2 cells compared to WI-38 cells, at high concentrations. By studying the cell death mechanism using flow-cytometry, AB extract was shown to induce apoptotic cell death at higher concentrations, as in the case of MDA-MB-231 and HePG-2 cells. In conclusion, the use of a modified AB for ß-glucan from Saccharomyces cerevisiae exerted a promising antimicrobial, immunomodulatory efficacy, and anti-cancer potential. Future research should focus on evaluating ß-glucan in various biological systems and elucidating the underlying mechanism of action.

Exosomes are the Driving Force in Preparing the Soil for the Metastatic Seeds: Lessons from the Prostate Cancer.

Exosomes are nano-membrane vesicles that various cell types secrete during physiological and pathophysiological conditions. By shuttling bioactive molecules such as nucleic acids, proteins, and lipids to target cells, exosomes serve as key regulators for multiple cellular processes, including cancer metastasis. Recently, microvesicles have emerged as a challenge in the treatment of prostate cancer (PCa), encountered either when the number of vesicles increases or when the vesicles move into circulation, potentially with an ability to induce drug resistance, angiogenesis, and metastasis. Notably, the exosomal cargo can induce the desmoplastic response of PCa-associated cells in a tumor microenvironment (TME) to promote PCa metastasis. However, the crosstalk between PCa-derived exosomes and the TME remains only partially understood. In this review, we provide new insights into the metabolic and molecular signatures of PCa-associated exosomes in reprogramming the TME, and the subsequent promotion of aggressive phenotypes of PCa cells. Elucidating the molecular mechanisms of TME reprogramming by exosomes draws more practical and universal conclusions for the development of new therapeutic interventions when considering TME in the treatment of PCa patients.

Melatonin inhibits breast cancer cell invasion through modulating DJ-1/KLF17/ID-1 signaling pathway.

Breast cancer is the most common neoplastic disorder diagnosed in women. The main goal of this study was to explore the effect of melatonin against breast cancer metastasis and compared this with the actions of taxol (a well-known chemotherapeutic drug), and the impact of their combination against breast cancer metastasis. Melatonin showed no cytotoxic effect while taxol showed antiproliferative and cytotoxic effects on MCF-7 and MDA-MB-231 cells. Furthermore, melatonin inhibited the generation of reactive oxygen species. Melatonin and taxol clearly decreased cell migration and invasion at low doses, especially those matching the normal physiological concentration at night. Melatonin and taxol markedly reduced DJ-1 and ID-1 and increased KLF17 messenger RNA and protein expression levels. The present results also showed that melatonin and taxol induced GSK3-ß nuclear and Snail cytosolic localization. These changes were accompanied by a concurrent rise in E-cadherin expression. The above data show that normal levels of melatonin may help in preventing breast cancer metastasis through inhibiting DJ-1/KLF17/ID-1 signaling pathway. The combination of melatonin and taxol is a potent candidate against breast cancer metastasis, better than using melatonin or taxol as a single drug.

Low doses of Paclitaxel repress breast cancer invasion through DJ-1/KLF17 signalling pathway.

Paclitaxel (taxol) is an important agent against many tumours, including breast cancer. Ample data documents that paclitaxel inhibits breast cancer metastasis while others prove that paclitaxel enhances breast cancer metastasis. The mechanisms by which paclitaxel exerts its action are not well established. This study focuses on the effect of paclitaxel, particularly the low doses on breast cancer metastasis and the mechanisms that regulate it. Current results show that, paclitaxel exerts significant cytotoxicity even at low doses in both MCF-7 and MDA-MB-231 cells. Interestingly, paclitaxel significantly inhibits cell invasion and migration, decreases Snail and increases E-cadherin mRNA expression levels at the indicated low doses. Furthermore, paclitaxel-inhibiting breast cancer metastasis is associated with down-regulation of DJ-1 and ID-1 mRNA expression level with a concurrent increase in KLF17 expression. Under the same experimental conditions, paclitaxel induces KLF17 and concurrently represses ID-1 protein levels. Our results show for the first time that paclitaxel inhibits breast cancer metastasis through regulating DJ-1/KLF17/ID-1 signalling pathway; repressed DJ-1 and ID-1 and enhanced KLF17 expression.