nsc-4347 and Carcinoma--Ehrlich-Tumor

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

Alcoholic extract of the fruits of the plant Piper longum and its component piperine was studied for their immunomodulatory and antitumor activity. Alcoholic extract of the fruits was 100% toxic at a concentration of 500 microg/ml to Dalton's lymphoma ascites (DLA) cells and 250 microg/ml to Ehrlich ascites carcinoma (EAC) cells. Piperine was found to be cytotoxic towards DLA and EAC cells at a concentration of 250 microg/ml. Alcoholic extract and piperine was also found to produce cytotoxicity towards L929 cells in culture at a concentration of 100 and 50 microg/ml, respectively. Administration of alcoholic extract of Piper longum (10 mg/dose/animal) as well as piperine (1.14 mg/dose/animal) could inhibit the solid tumor development in mice induced with DLA cells and increase the life span of mice bearing Ehrlich ascites carcinoma tumor to 37.3 and 58.8%, respectively. Administration of Piper longum extract and piperine increased the total WBC count to 142.8 and 138.9%, respectively, in Balb/c mice. The number of plaque forming cells also enhanced significantly by the administration of the extract (100.3%) and piperine (71.4%) on 5th day after immunization. Bone marrow cellularity and alpha-esterase positive cells were also increased by the administration of Piper longum extract and piperine.

Topics: Adjuvants, Immunologic; Alkaloids; Animals; Antineoplastic Agents, Phytogenic; Benzodioxoles; Carcinoma, Ehrlich Tumor; Mice; Mice, Inbred BALB C; Piper; Piperidines; Plant Extracts; Polyunsaturated Alkamides; Sheep; Xenograft Model Antitumor Assays