1-5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan and Leukemia

A novel approach to circumvent multidrug resistance is hybridization of natural products in dimers. We analyzed homodimers of two artesunic acid molecules and heterohybrids of artesunic acid and betulin in human CCRF-CEM and multidrug-resistant P-glycoprotein-overexpressing CEM/ADR5000 leukemia cells. Multidrug-resistant cells were not cross-resistant to the novel compounds. Collateral sensitivity was observed for artesunic acid homodimer. Artesunic acid and artesunic acid homodimer induced G0/G1 cell cycle arrest, apoptosis, and formation of reactive oxygen species.

Topics: Apoptosis; Artemisinins; Cell Cycle; Cell Line, Tumor; Cell Survival; Drug Resistance, Neoplasm; Flow Cytometry; Formazans; Humans; Leukemia; Magnetic Resonance Spectroscopy; Reactive Oxygen Species; Spectrometry, Mass, Electrospray Ionization; Succinates; Triterpenes

Plantago major linn. and P. asiatica Linn. (Plantaginaceae) are commonly used as folk medicine in Taiwan for treating infectious diseases related to the respiratory, urinary and digestive tracts. In this study, we investigated the antiviral, cytotoxic and immunomodulatory activities of hot water extracts of these two species in vitro on a series of viruses, namely herpesviruses (HSV-1 and HSV-2), adenoviruses (ADV-3, ADV-8 and ADV-11), and on various human leukemia, lymphoma and carcinoma cells with XTT, BrdU and IFN-gamma kits. Results showed that hot water extract of P. asiatica possessed significant inhibitory activity on the proliferation of lymphoma (U937) and carcinoma (bladder, bone, cervix, kidney, lung and stomach) cells and on viral infection (HSV-2 and ADV-11). P. major and P. asiatica both exhibited dual effects of immunodulatory activity, enhancing lymphocyte proliferation and secretion of interferon-gamma at low concentrations (< 50 microg/ml), but inhibiting this effect at high concentration (> 50 microg/ml). The present study concludes that hot water extracts of P. major and P. asiatica possess abroad-spectrum of antileukemia, anticarcinoma and antiviral activities, as well as activities which modulate cell-mediated immunity. Further investigations to elucidate the active component(s) of P. asiatica and P. major and to evaluate their clinical application are warranted.

Topics: Adenoviridae; Adjuvants, Immunologic; Antineoplastic Agents, Phytogenic; Antiviral Agents; Drug Screening Assays, Antitumor; Enzyme-Linked Immunosorbent Assay; Formazans; Herpesvirus 1, Human; Humans; Interferon-gamma; Leukemia; Lymphocyte Activation; Plant Extracts; Plantago; Tumor Cells, Cultured

In order to establish a new more rapid, safe and sensitive colorimetric assay for the proliferation of leukemic cells, MTS/pms has been developed. This automated colorimetric assay is based on the characteristic of viable and metabolically active leukemic cells to cleave MTS/pms into a water-soluble product whose optical density is determined at 492 nm by an automated microtiter-plate reader photometer. The results indicated that only active leukemic cells cleaved MTS/pms into product measured, and dead cells did not reduce MTS/pms. A linear relations hip were found between the viable cell number and optical density of MTS/pms cleaved by HL-60 and K562 cell (r = 0.963). Compared with MTT and INT assays, the reduced product of MTS/pms is water-soluble. It is concluded that MTS/pms colorimetric assay is more rapid, accurate and sensitive for the bioassay of proliferation of leukemic cells.

Topics: Cell Division; Colorimetry; Formazans; HL-60 Cells; Humans; K562 Cells; Leukemia; Methylphenazonium Methosulfate; Tetrazolium Salts; Thiazoles