Báo cáo khoa học: The benzophenanthridine alkaloid sanguinarine perturbs microtubule assembly dynamics through tubulin binding A possible mechanism for its antiproliferative activity Manu Lopus and Dulal Panda

The Benzophenanthridine Alkaloid Sanguinarine Perturbs Microtubule Assembly Dynamics Through Tubulin Binding: A Possible Mechanism for Its Antiproliferative Activity

Authors: Manu Lopus and Dulal Panda

Field: Biosciences and Bioengineering, Indian Institute of Technology Bombay, India

Document Content: This study investigates the antiproliferative activity of sanguinarine, a benzophenanthridine alkaloid, and proposes a mechanism involving its interaction with tubulin and disruption of microtubule assembly dynamics. Sanguinarine was found to inhibit the proliferation of HeLa cells with a notable IC50 value. Unlike many other microtubule-targeting agents, sanguinarine does not appear to arrest the cell cycle at mitosis. Instead, it effectively depolymerizes microtubules in both interphase and mitotic cells, leading to disorganized chromosome structure and cell death. The research also demonstrates that sanguinarine binds to tubulin, inducing conformational changes and copolymerizing into microtubule polymers. These findings suggest that sanguinarine’s antiproliferative effect is primarily mediated by its ability to destabilize microtubule dynamics, offering a distinct mechanism compared to existing microtubule-depolymerizing drugs.

Detailed Table of Contents:

• Keywords
• Correspondence
• Abstract
• Introduction
• Results
• Discussion
• Experimental Procedures
• Materials
• Cell Culture and Proliferation Assay
• Immunofluorescence Microscopy
• Determination of Mitotic Indices and Live/Dead Cells
• Purification of Tubulin
• Spectral Measurements
• Inhibition of Paclitaxel-Induced Polymerization of Tubulin
• Transmission Electron Microscopy
• Copolymerization of Sanguinarine and Tubulin
• Effects of Sanguinarine on Tubulin–ANS Complex Fluorescence
• Acknowledgements
• References