lignans and Carcinoma--Ehrlich-Tumor

Honokiol (HK) is a common herbal medicine extracted from magnolia plants. Low aqueous solubility and limited bioavailability of HK have hindered its clinical application, especially for cancer treatment. Nano-drug delivery system has the potential to enhance HK delivery and therefore, enhance its anti-cancer activity.. The study's aim is to design novel PEGylated-PLGA polymeric nanocapsules (NCs) for HK delivery to breast tumor-bearing mice after systemic administration.. Formulation of different HK-loaded NCs and their physio-chemical characterization were optimized through the use of different formulation variables. The antitumor activity of the HK-loaded NCs was investigated both in vitro using MCF-7 and EAC breast cancer cell lines and in vivo using solid Ehrlich carcinoma (SEC) breast cancer model.. The optimum HK-loaded NCs were prepared from 15% PEG-PLGA diblock copolymer and exhibited the lowest nano size of 125 nm, smooth spherical morphology, highest drug loading of 94% and highest cellular uptake into breast cancer cells. HK-loaded PEGylated NCs can effectively inhibit the in vitro cell growth of breast cancer cells by 80.2% and 58.1% compared to 35% and 31% with free HK in the case of MCF-7 and EAC, respectively. HK-loaded NCs inhibited SEC tumor growth by 2.3 fold significantly higher than free HK, in vivo.. The designed drug delivery system encapsulating HK exhibited a pronounced decrease in tumor growth biomarkers meanwhile proved its safety in animals. Therefore, 15% PEGylated HK-loaded NCs may act as a promising new approach for breast cancer treatment.

Topics: Animals; Antineoplastic Agents, Phytogenic; Biphenyl Compounds; Breast Neoplasms; Carcinoma, Ehrlich Tumor; Drug Delivery Systems; Female; Humans; Lignans; MCF-7 Cells; Mice; Micelles; Nanocapsules; Polyethylene Glycols; Polyglactin 910; Solubility; Xenograft Model Antitumor Assays

Despite numerous studies with the Piper genus, there are no previous results reporting in vitro or in vivo Piper regnellii (Miq.) C. DC. var. regnellii anticancer activity. The aim of this study was to investigate P. regnellii in vitro and in vivo anticancer activity and further identify its active compounds. In vitro antiproliferative activity was evaluated in 8 human cancer cell lines: melanoma (UACC-62), breast (MCF7), kidney (786-0), lung (NCI-H460), prostate (PC-3), ovary (OVCAR-3), colon (HT29), and leukemia (K-562). Total growth inhibition (TGI) values were chosen to measure antiproliferative activity. Among the cell lines evaluated, eupomatenoid-5 demonstrated better in vitro antiproliferative activity towards prostate, ovary, kidney, and breast cancer cell lines. In vivo studies were carried out with Ehrlich solid tumor on Balb/C mice treated with 100, 300, and 1000 mg/kg of P. regnellii leaves dichloromethane crude extract (DCE), with 30 and 100 mg/kg of the active fraction (FRB), and with 30 mg/kg of eupomatenoid-5. The i. p. administration of DCE, FRB, and eupomatenoid-5 significantly inhibited tumor progression in comparison to control mice (saline). Therefore, this study showed that neolignans of Piper regnellii have promising anticancer activity. Further studies will be undertaken to determine the mechanism of action and toxicity of these compounds.

Topics: Animals; Antineoplastic Agents; Benzofurans; Carcinoma, Ehrlich Tumor; Cell Line, Tumor; Female; Humans; Lignans; Male; Mice; Mice, Inbred BALB C; Phenols; Piper; Plant Extracts; Plant Leaves

The antitumoural properties of grandisin, a tetrahydrofuran neolignan from Piper solmsianum, were investigated by in-vitro and in-vivo assays using the Ehrlich ascites tumoural (EAT) model.. Viability of the tumour cells was evaluated by Trypan blue exclusion and MTT methods, after incubation with grandisin (0.017-2.3 microm). The effects of grandisin on the activity of caspase-3, -6, -8, and -9 were also investigated using colorimetric protease kits. In-vivo studies were performed in EAT-bearing mice treated intraperitoneally with 2.5, 5 or 10 mg/kg grandisin for 10 days.. Grandisin inhibited the growth of EAT cells, by both methods, with IC50 values less than 0.25 microm. The results showed that the activity of all the caspases studied increased in grandisin-treated cells, when compared with control, non-treated cells. Administering grandisin to EAT-bearing mice increased survival of the animals, in a dose-dependent manner. Simultaneously, we detected a 66.35% reduction of intraperitoneal tumour cell burden in the animals treated with 10 mg/kg grandisin. Additionally, in these animals, the marked increase of vascular endothelial growth factor (VEGF) levels, induced by EAT development, was decreased with treatment with grandisin, resulting in a reduction of 32.1% of VEGF levels in the peritoneal washing supernatant, when compared with the control.. The results demonstrated that grandisin induced in-vitro cytotoxicity and antiangiogenic effects in mice while it acted against tumour evolution, prolonging host survival.

Topics: Angiogenesis Inhibitors; Animals; Antineoplastic Agents, Phytogenic; Carcinoma, Ehrlich Tumor; Caspases; Cell Proliferation; Dose-Response Relationship, Drug; Furans; Inhibitory Concentration 50; Lignans; Male; Mice; Neoplasms, Experimental; Neovascularization, Pathologic; Phytotherapy; Piper; Plant Extracts; Plant Leaves; Vascular Endothelial Growth Factor A