A paper on compounds that bind to the quadruple helix structure and exhibit anticancer activity has been published in the British scientific journal Scientific Reports.

A research group led by Dr. Das Sinjan, Associate Professor Shuntaro Takahashi and Professor Naoki Sugimoto at the Frontier Institute for Biomolecular Engineering Research (FIBER), Konan University, in collaboration with Dr. Sudipta Bhowmik at the Mahatma Gandhi Medical Advanced Research Institute, Sri Balaji Vidyapeeth University (SBV University, MGMARI), India, has elucidated the mechanism of action of compounds that exhibit anticancer activity by binding to the intracellular i-motif DNA, a four-fold helical structure. A research paper resulting from this project has been published in Scientific Reports.

While medical technology has made remarkable progress in recent years, cancer is still the leading cause of death in Japan. Therefore, the development of superior anti-cancer drugs to eradicate cancer has become one of the biggest challenges of this century. Many anticancer agents act on nucleic acids (DNA and RNA) in cells, which may cause normal cells to become cancerous by damaging the nucleic acids of normal cells. On the other hand, substances suspected to be carcinogenic, on the contrary, have the potential to function as anticancer agents, and may be important drug candidates for anticancer agents. In this study, FIBER’s research group, in collaboration with Dr. Sudipta Bhowmik of India-core, SBV Univ. MGMARI, analyzed the interaction between crystal violet, one of the dyes suspected to be carcinogenic, and DNA of genes that are activated in various cancer cells. As a result, they found that crystal violet specifically binds to the i-motif type DNA tetraplex, which is a part of the DNA of BCL2, a type of oncogene. Mutational analysis and molecular dynamics calculations suggest that crystal violet specifically interacts with a portion of the BCL2 gene called the loop region in the i-motif structure. To investigate the anticancer properties of crystal violet, crystal violet was added to human breast cancer cells (MCF-7) and significantly reduced the expression level of the BCL2 gene, indicating that crystal violet acts as an anticancer agent targeting the DNA fourfold helix structure. Until now, there have been few reports of molecules that bind to specific i-motif type DNA tetraplexes and regulate gene expression. Therefore, crystal violet is considered to act as an anticancer drug with a novel mechanism of action to suppress the expression of specific oncogenes by targeting i-motif type DNA. Based on the results of this study, we expect to develop new anticancer agents with reduced carcinogenicity and side effects by designing molecules that improve the selectivity of the i-motif of crystal violet.

We will continue to synthesize and analyze artificial molecules that control nucleic acid structures in collaboration with our overseas core members.

【Scientific Reports (electronic edition)】Click here for the link to the published page.

【Published Articles】

“Theranostic approach to specifically targeting the interloop region of BCL2 i-motif DNA by crystal violet”
S. Das, S. Takahashi, T. Ohyama, S. Bhowmik, and N. Sugimoto, Scientific Reports, 13, 14338 (2023).