macelignan and Breast-Neoplasms

Paclitaxel (PTX) is one of the drugs of choice in the treatment of breast and lung cancer. However, its severe side effects, including mielosuppression, cardiotoxicity and neurotoxicity, frequently cause treatment to be discontinued. Solid lipid nanoparticles (NPs) of glyceril tripalmitate (tripalmitin) loaded with PTX (Tripalm-NPs-PTX) including modifications by the addition of hexa(ethylene glycol), β-cyclodextrin and macelignan were developed. All NPs-PTX formulations displayed excellent hemocompatibility and significantly enhanced PTX antitumor activity in human breast (MCF7, MDAMB231, SKBR3 and T47D) and lung (A549, NCI-H520 and NCI-H460) cancer cells. Tripalm-NPs-PTX decreased PTX IC

Topics: Antineoplastic Agents; beta-Cyclodextrins; Breast Neoplasms; Cell Line; Female; Humans; Lignans; Lung Neoplasms; MCF-7 Cells; Nanoparticles; Neoplastic Stem Cells; Paclitaxel; Polyethylene Glycols; Spheroids, Cellular; Triglycerides; Tumor Cells, Cultured

The effect of macelignan, a phytoestrogen, on P-gp function was investigated using multidrug resistant cancer cells overexpressing P-gp (NCI/ADR-RES) and the fluorescent P-gp substrates, daunorubicin and rhodamine 123. Macelignan (40 microM) increased the cellular accumulation of daunorubicin by approximately threefold in NCI/ADR-RES cells, whereas it did not alter the cellular accumulation of daunorubicin in MCF-7/sensitive cells. Similarly, the presence of macelignan also enhanced significantly (P < 0.05) the cellular accumulation of rhodamine 123 in a concentration-dependent manner in NCI/ADR-RES cells. Furthermore, cancer cells were more susceptible to the cytotoxicity of vinblastine, a P-gp substrate, in the presence of macelignan. Those results suggest that macelignan has inhibitory effects on P-gp mediated cellular efflux. However, P-gp activity did not affect the cellular accumulation of macelignan itself. Taken all together, macelignan was identified as a novel inhibitor of P-gp activity and may be a promising lead compound for the rational design of more efficacious drugs to reverse multidrug resistance in cancer.

Topics: Adenocarcinoma; Analysis of Variance; Antineoplastic Agents, Phytogenic; ATP Binding Cassette Transporter, Subfamily B; Biological Transport, Active; Breast Neoplasms; Cell Line, Tumor; Cell Survival; Daunorubicin; Dose-Response Relationship, Drug; Drug Design; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Synergism; Female; Fluorescent Dyes; Growth Inhibitors; Humans; Lignans; Phytoestrogens; Phytotherapy; Rhodamine 123; Vinblastine

Five new dibenzylbutane type lignans (1-5) were isolated from the stem bark of Iryanthera lancifolia. Their structures were determined by extensive 1D and 2D NMR spectroscopic studies and chemical evidence. Seventeen of the isolated compounds were tested for their estrogenic activities in the estrogen responsive human breast cancer cell line MCF-7 BUS using the E-Screen proliferation assay. Cell proliferation was evaluated by the SRB assay to calculate the estrogenic parameters. The majority of the compounds induced a mitogenic response. This effect, given as Relative Proliferative Effect (RPE) to reference estrogen 17beta-estradiol (E(2)), ranged between 14% and 84%.

Topics: Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Female; Humans; Lignans; Molecular Structure; Phytoestrogens