Gene expression profiles of some prognostic markers in a human breast cell line (MCF7) exposed to Curcumin nanoparticles and nanocapsules

Introduction: Worldwide, cancer is a significant public health problem. Curcumin exhibits anti-inflammatory, antiproliferative, and anticancer properties when used in medicine. Investigated study for Curcumin's chemopreventive mechanism against human malignancies, this research examined the cellular and molecular alterations generated by curcumin modified compound in breast cancer (MCF-7) cell lines. Oncogenic EGFR and VEGFR2 mutations lead to the formation, invasion, and maintenance of malignant phenotypes in humans, including breast cancer. Studied prognostic markers such as C-myc and Ki67 in breast cancer, and the apoptotic gene as Caspase-3 have been done. Aim of the work: The purpose of this study is to determine the therapeutic efficacy of curcumin nanoparticles and nanocapsules in breast cancer cell lines (MCF7). Materials and methods: We used real-time PCR to assess the expression of the C-myc, Ki67, EGFR, VEGFR2, and Caspase-3 genes in MCF7 cells treated with Curcumin nanoparticles and nanocapsules. Results: Curcumin nanoparticles and nanocapsules boosted apoptotic cell populations considerably regardless of the nanotechnology used. Additionally, the mRNA expression analysis results indicated that the mechanism activated by curcumin nanocapsules involved the upregulation of the oncogenes EGFR and VEGFR2. In comparison to curcumin nanoparticles, curcumin nanocapsules significantly reduced the expression of Ki67 and c-myc mRNAs in breast cancer cells. The mRNA expression study revealed that curcumin nanocapsules produce an increase in the apoptotic Caspase-3 gene production compared to cells treated with curcumin nanoparticles. Conclusion: This work demonstrates that curcumin nanoparticles created using a novel mechanical process can be employed successfully as an anticancer agent. These findings add to our understanding of the molecular mechanisms behind curcumin nanocapsules' anticancer activity in breast cancer.

Curcumin Nanoparticles Enhance Antioxidant Efficacy of Diclofenac Sodium in Experimental Acute Inflammation

We investigated the in vivo effect of curcumin nanoparticles (nC) in addition to diclofenac sodium on local edema and oxidative stress parameters in carrageenan-induced paw edema on rats. Seven groups were investigated: control group (C), the acute inflammation (AI) group, an AI group treated with Diclofenac (AID, 5 mg/kg b.w. Diclofenac sodium), two AI groups treated with cC (conventional Curcumin)—AIC200 and AIcC200D (D = Diclofenac, 200 represent the concentration of active substance expressed in mg/kg b.w.), and two AI groups with nC (Curcumin nanoparticles)—AIC200 and AIcC200D. Serum and tissue oxidative stress was assessed by measuring five parameters. Curcumin nanoparticles alone and in combination with D better reduced the paw edema than D alone (p < 0.027). The rats treated with D and nC (AIcC200D) had the highest inhibition percentage on edema, reaching the maximum level of inhibition (81%) after 24 h. Conventional curcumin and nC presented antioxidant effects in acute inflammation, with significantly better results obtained for nC. The pro-oxidant markers were reduced up to 0.3 by the cC and up to 0.4 times by the nC and both solutions increased the antioxidant markers up to 0.3 times. The nC enhanced the antioxidative efficacy of D, as this combination reduced the pro-oxidant markers up to 1.3 times. Curcumin nanoparticles could represent a therapeutic option in association with classical nonsteroidal anti-inflammatory medication in acute inflammation, as they might offer a reduction of drug dose and possible limitation of their associated side effects.

Study on Apoptosis of Prostate Cancer Cells Induced by IκBα Overexpression Synergistic with Poly (Lactic-Co-Glycolic Acid)-Curcumin Nanoparticles

Objective. To investigate the synergistic effects of IκBα overexpression and poly (lactic-co-glycolic acid)-curcumin nanoparticles (PLGA-Cur-NPs) on prostate cancer (PC) and reveal the underlying mechanisms of cooperative sensitization induced by curcumin. Methods. Proliferation and apoptosis rate in IκBα overexpressed and PLGA-Cur-NPs-treated PC cells were detected by MTT and flow cytometry assay. The expression levels of IκBα, apoptosis-related, and signaling proteins were measured by western blotting assay. Results. PC cell proliferation was significantly inhibited by the overexpression of IκBα. The apoptosis rate of PC cells was significantly increased at a high concentration of curcumin exposure, while the activation of NF-κB pathway was obviously inhibited. In addition, PLGA-Cur-NPs treatment synergistic with IκBα overexpression enhanced the apoptosis of PC cells by suppressing the NF-κB pathway activation. Conclusion. IκBα overexpression synergistic with PLGA-Cur-NPs could obviously inhibit proliferation, induce apoptosis, and suppress the activation of NF-κB pathway in PC cells. These findings may provide an experimental basis to establish the tumor gene therapy combined with traditional Chinese medicine treatment, thus promoting the clinical application of both tumor gene therapy and anti-tumor Chinese medicine.

Protective Effect of Natural Antioxidant, Curcumin Nanoparticles, and Zinc Oxide Nanoparticles against Type 2 Diabetes-Promoted Hippocampal Neurotoxicity in Rats

Numerous epidemiological findings have repeatedly established associations between Type 2 Diabetes Mellitus (T2DM) and Alzheimer’s disease. Targeting different pathways in the brain with T2DM-therapy offers a novel and appealing strategy to treat diabetes-related neuronal alterations. Therefore, here we investigated the capability of a natural compound, curcumin nanoparticle (CurNP), and a biomedical metal, zinc oxide nanoparticle (ZnONP), to alleviate hippocampal modifications in T2DM-induced rats. The diabetes model was induced in male Wistar rats by feeding a high-fat diet (HFD) for eight weeks followed by intraperitoneal injection of streptozotocin (STZ). Then model groups were treated orally with curcumin, zinc sulfate, two doses of CurNP and ZnONP, as well as metformin, for six weeks. HFD/STZ-induced rats exhibited numerous biochemical and molecular changes besides behavioral impairment. Compared with model rats, CurNP and ZnONP boosted learning and memory function, improved redox and inflammation status, lowered Bax, and upregulated Bcl2 expressions in the hippocampus. In addition, the phosphorylation level of the MAPK/ERK pathway was downregulated significantly. The expression of amyloidogenic-related genes and amyloid-beta accumulation, along with tau hyperphosphorylation, were lessened considerably. In addition, both nanoparticles significantly improved histological lesions in the hippocampus. Based on our findings, CurNP and ZnONP appear to be potential neuroprotective agents to mitigate diabetic complications-associated hippocampal toxicity.

CD123-Targeted Nano-Curcumin Molecule Enhances Cytotoxic Efficacy in Leukemic Stem Cells

Acute myeloblastic leukemia (AML) is a disease with a high rate of relapse and drug resistance due to the remaining leukemic stem cells (LSCs). Therefore, LSCs are specific targets for the treatment of leukemia. CD123 is specifically expressed on LSCs and performs as a specific marker. Curcumin is the main active compound of a natural product with low toxicity for humans. It has been reported to inhibit leukemic cell growth. However, curcumin is practically insoluble in water and has low bioavailability. In this study, we aimed to formulate curcumin nanoparticles and conjugate with the anti-CD123 to overcome the low water solubility and improve the targeting of LSCs. The cytotoxicity of both curcumin-loaded PLGA/poloxamer nanoparticles (Cur-NPs) and anti-CD123-curcumin-loaded PLGA/poloxamer nanoparticles (anti-CD123-Cur-NPs) were examined in KG-1a cells. The results showed that Cur-NPs and Cur-NPs-CD123 exhibited cytotoxic effects on KG-1a cells with the IC50 values of 74.20 ± 6.71 and 41.45 ± 5.49 µM, respectively. Moreover, anti-CD123-Cur-NPs induced higher apoptosis than Cur-NPs. The higher uptake of anti-CD123-Cur-NPs in KG-1a cells was confirmed by using flow cytometry. In conclusion, the anti-CD123-Cur-NPs formulation improved curcumin’s bioavailability and specific targeting of LSCs, suggesting that it is a promising drug delivery system for improving the therapeutic efficacy against AML.

Ameliorative effect of curcumin and zinc oxide nanoparticles on multiple mechanisms in obese rats with induced type 2 diabetes

The present study was carried out to investigate the therapeutic effect of synthesized naturally compounds, curcumin nanoparticles (CurNPs) and metal oxide, zinc oxide nanoparticles (ZnONPs) on a high-fat diet (HFD)/streptozotocin (STZ)-induced hepatic and pancreatic pathophysiology in type 2 diabetes mellitus (T2DM) via measuring AKT pathway and MAPK pathway. T2DM rats were intraperitoneally injected with a low dose of 35 mg/kg STZ after being fed by HFD for 8 weeks. Then the rats have orally received treatments for 6 weeks. HFD/STZ-induced hepatic inflammation, reflected by increased phosphorylation of p38-MAPK pathway’s molecules, was significantly decreased after nanoparticle supplementation. In addition, both nanoparticles significantly alleviated the decreased phosphorylation of AKT pathway. Further, administration of ZnONPs, CurNPs, conventional curcumin, and ZnSO4 (zinc sulfate), as well as metformin, effectively counteracted diabetes-induced oxidative stress and inflammation in the internal hepatic and pancreatic tissues. Based on the results of the current study, ZnONPs and CurNPs could be explored as a therapeutic adjuvant against complications associated with T2DM. Both nanoparticles could effectively delay the progression of several complications by activating AKT pathway and down-regulating MAPK pathway. Our findings may provide an experimental basis for the application of nanoparticles in the treatment of T2DM with low toxicity.

Improving Curcumin Bioavailability: Current Strategies and Future Perspectives

Curcumin possesses a plethora of interesting pharmacological effects. Unfortunately, it is also characterized by problematic drug delivery and scarce bioavailability, representing the main problem related to the use of this compound. Poor absorption, fast metabolism, and rapid systemic clearance are the most important factors contributing to low curcumin levels in plasma and tissues. Accordingly, to overcome these issues, numerous strategies have been proposed and are investigated in this article. Due to advances in the drug delivery field, we describe here the most promising strategies for increasing curcumin bioavailability, including the use of adjuvant, complexed/encapsulated curcumin, specific curcumin formulations, and curcumin nanoparticles. We analyze current strategies, already available in the market, and the most advanced technologies that can offer a future perspective for effective curcumin formulations. We focus the attention on the effectiveness of curcumin-based formulations in clinical trials, providing a comprehensive summary. Clinical trial results, employing various delivery methods for curcumin, showed that improved bioavailability corresponds to increased therapeutic efficacy. Furthermore, advances in the field of nanoparticles hold great promise for developing curcumin-based complexes as effective therapeutic agents. Summarizing, suitable delivery methods for this polyphenol will ensure the possibility of using curcumin-derived formulations in clinical practice as preventive and disease-modifying therapeutics.