Development of a novel liposomal nanoparticle formulation of cisplatin to breast cancer therapy

Cisplatin is one of the conventional drugs used in chemotherapy which has a potent antitumor function. However, due to the dangerous side effects, including the damage to DNA of the normal cells, its clinical use is limited. The aim of this study was to prepare and characterize nanoliposome containing cisplatin. We optimized liposome formulations through the modification of the proportion of SPC80 (soybeanphospholipids with 75 phosphatidylcholine) and cholesterol content. Then, novel PEGylated liposomal formulations containing SPC80: cholesterol: DSPE-mPEG (at ratios of 85:10:5) were designed and developed to serve as a therapy to achieve more improved pharmaceutical efficiency. Zeta Sizer showed that PEGylated nanoliposomes had a mean diameter of 119.7 ± 2.1 nm, a zeta potential of �26.03 ± 1.34 mV, and entrapment efficiency of 96.65 ± 3. The optimum formulations represented sustained, thermo-sensitive release, and augmented cellular uptake. The cytotoxic effect of the liposomal drug was higher than the free medication drug that confirmed the efficiency of cellular uptake. This study suggests that nanoliposome-loaded cisplatin plays a vital role in improving drug efficacy and the reduction of dosage. © 2020 Wiley Periodicals, Inc

Vanadium complex induced apoptosis in HepG2 Cells by the up-regulation of p53, p21, and Caspase-8

OBJECTIVE: The anti-cancer effects of 4-bromo-2-(((5-chloro-2-hydroxyphenyl) imino) methyl) phenol ([IV(L)] complex) have been verified. The main mechanisms used by the [IV(L)] complex to induce apoptosis in cancer cells have yet to be clarified. This study has been designed to explore the effects of the [IV(L)] complex on the expression of apoptosis-related genes, including P53, caspase-8, bax, bcl-2, bim, P21, and bid, in human liver hepatocellular carcinoma (HepG2) cell lines and mouse fibroblast cells (L929), as normal cells. MATERIALS AND METHODS: The RPMI medium was used to culture L929 and HepG2 cells at the IC50 concentration of the [IV(L)] complex. The expression of some apoptosis-related genes (p53, caspase-8, bax, bcl-2, bim, P21, and bid) was evaluated before and after 48 h from treating the cells by the [IV(L)] complex at the IC50 concentration using the real-time PCR. Data analyzed via SPSS 18 (SPSS Inc., Chicago, IL, USA) software and p< 0.05 was designated as the significant level. RESULTS: The [IV(L)] complex increased the mRNA expression levels of P53 and P21 genes in HepG2 (p< 0.05) cells. In addition, the expression levels of caspase-8 and bid decreased after treatment with the [IV(L)] complex (p= 0.05), and the expression levels of bax and bim genes remained fixed in the HepG2-treated cells. In L929 cells, the mRNA expression levels of P53, caspase-8, bim, P21, and bid increased, with the expression level of the bax gene significantly decreased after 48 h from treatment with the [IV(L)] complex(p= 0.001). CONCLUSIONS: The Vanadium [IV(L)] complex induced apoptosis in HepG2 cells using the P53-P21 pathway-dependent method. In L929 cells, the mRNA expression levels of caspase-8 and bid were up-regulated in the treated cells. Therefore, it seems that apoptosis is triggered by both the P53-P21 pathway and the extrinsic apoptotic pathway in L929 cells

The hydroalcoholic extract of Baneh leaves (Pistacia atlantica) induces apoptosis in the breast cancer cells

Objective: Breast cancer is one of the most prevalent cancers among women, which has widespread in recent years in Iran. Wild Pistachio (Pistacia Atlantica), known as Baneh in Iran, is a medicinal plant. The present study aimed to test the anti-tumor properties of the hydro-alcoholic extract of Baneh leaves in MCF-7 breast cancerous cells. Materials and Methods: The MTT assay, morphologic analysis, and DNA fragmentation assay were conducted to evaluate the inhibitory effects of the Baneh leaves hydro-alcoholic extract on the proliferation of cancerous cells (MCF-7) and normal ones (L929). The mRNA expression levels of some apoptotic genes, including p53, caspase-8, caspase-3, bax, and bcl-2 were measured by real-time PCR. Results: Data analysis demonstrated that the IC50 value for MCF-7 and L929 cells after 48-hours treatment with extract was 250 g/mL and 400 g/mL, respectively. The morphologic analysis and DNA fragmentation assay confirmed the occurrence of apoptosis in both L929 and MCF-7 cells after treatment with the Baneh extract at IC50 concentration. It gives the idea that up-regulation of caspase-8, caspase-3, p53, and bax genes decrease in the expression of bcl-2 gene, showing that the Baneh extract induces apoptosis through both intrinsic and extrinsic pathways of programmed cell death in MCF-7 cells. Conclusions: Breast cancer cells are more sensitive to the treatment with the Baneh extract compared to normal cells, making this extract a promising candidate to be used in the preparation of anti-cancer drugs against breast cancer cells with fewer side effects on healthy cells