Molecular and Cellular PharmacologyMembrane interaction of an antitumor antibiotic, mithramycin, with anionic phospholipid vesicles
Section snippets
Materials and methods
MTR, MgCl2 solution (4.9 mol/L), DMPC, PS, CF, Sephadex G-50, Triton X-100, and Tris were purchased from the Sigma Chemical Co. DMPA was from Fluka. Solvents used were of spectroscopic grade. Deionized water from a Milli Q source (Millipore Corp.) was used for preparation of the buffer and all other solutions. (MTR)2Mg2+ complex was prepared by incubating 10–20 μM MTR with 10 mM Mg2+ for 1 hr.
Fluorescence measurements were performed in a Shimadzu RF-540 spectrofluorometer using both 2- and
Results
Fluorescence emission spectra of MTR both in the aqueous buffer and in two different concentrations of DMPC/DMPA SUV are shown in Fig. 1. Maximum emission of MTR was at 536 nm in aqueous buffer; it was blue-shifted by 2 nm in phospholipid vesicles, emitting maximally at 534 nm. Enhancement of the intensity of MTR fluorescence was observed in the presence of increasing concentrations of the phospholipid vesicles. Similar enhancement of fluorescence intensity also was observed when phospholipid
Discussion
The antitumor activities of antibiotics such as actinomycin, chromomycin, and the anthracycline group of antibiotics are often attributed directly to their interaction with DNA 28, 29. However, studies with other antitumor antibiotics, such as doxorubicin, indicate that the drug can be cytotoxic even without entering the cells 30, 31. A growing body of literature indicates that the cytotoxicity could be related directly to drug–membrane and in particular to drug–lipid interactions [31]. Studies
Acknowledgements
We thank Dr. Dipak Dasgupta for his keen interest in this work and a critical reading of the manuscript. We also thank Dr. Amitabha Chattopadhyay of CCMB for many fruitful suggestions in the preparation of the manuscript. We acknowledge both scientific and technical support from the electron microscope facility of SINP. Sangita Majee acknowledges a Senior Research Fellowship from CSIR, India.
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