Korea University: A new secret of cisplatin discovered

A new secret of cisplatin, a representative anticancer drug that has been widely used for decades, has been revealed.

A research team led by Professor Hong Seok-cheol of the Department of Physics of Korea University College of Science and composed of members from KU’s Department of Physics and the Center for Molecular Spectroscopy and Dynamics of the Institute for Basic Science elucidated at the molecular level the mechanism of action of cisplatin, a representative anticancer drug. This research was funded by the Individual Research (Mid-Career Researcher) Program of the Ministry of Science and ICT and the Institute for Basic Science. Its findings were published in Nucleic Acids Research on November 24.

In the human body, there is enough DNA to wrap around the earth 2.5 million times. However, the double-helix DNA molecule is tightly compacted into the form of chromatin and squeezed into a tiny nucleus inside cells, wound up in molecular spools that are invisible to the naked eye. The growth and death of cells in the human body is regulated through a reversible remodeling process in which these chromatin structures are loosened and tightened. The new finding of this research indicates that cisplatin functions like a fixer and could inhibit nucleosome remodeling required for normal biological functions.

The research team paid attention to the fact that most DNA molecules present in cells are in the form of chromatin. Based on the possibility that chromatin is the primary target of cisplatin, the research team precisely measured at the molecular level the change in the physical properties of chromatin when bound by cisplatin. Through their measurements, the research team confirmed that cisplatin-bound chromatin, which would otherwise be reversibly renewed (remodeled) like a spring, permanently lost elasticity and did not respond to any strong physical or chemical stimuli, such as a strong pull or highly concentrated saline water.

Using magnetic tweezers, it was possible for the research team to capture these changes in chromatin in real time at the molecular level.

This research confirmed cisplatin’s strong anticancer activity by fastening chromatin in an in vivo environment while proposing magnetic tweezers as a device for measuring the efficacy and development of DNA-targeted anticancer drugs. The research was conducted in collaboration with Professor Kim Jun-gon of Korea University; Kim Jae-hoon and Professor Song Ji-joon’s team from the Korea Advanced Institute of Science and Technology; and Professor Lee Nam-Kyung’s team from Sejong University.

“This study is significant as it suggests that the pharmacological target of cisplatin could be chromatin, a more condensed upper structure, rather than pure DNA. Therefore, I expect that this finding can serve as a clue to the measurement of the efficacy and mechanism of action of various anticancer drugs targeting DNA and the design of powerful anticancer drugs,” said Professor Hong.

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