Effect of lonidamine derivatives on the inhibition of transformed cell area expansion

Megumi Aoyama; Taiki Homma; Ryohto Koharazawa; Yoshitomo Suhara; Kentaro Semba

doi:10.1016/j.bbrep.2023.101480

Effect of lonidamine derivatives on the inhibition of transformed cell area expansion

Biochem Biophys Rep. 2023 Apr 29:34:101480. doi: 10.1016/j.bbrep.2023.101480. eCollection 2023 Jul.

Authors

Megumi Aoyama¹, Taiki Homma², Ryohto Koharazawa², Yoshitomo Suhara², Kentaro Semba^{1

3}

Affiliations

¹ Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering, Waseda University, 2-2 Wakamatsu-cho, Shinjuku-ku, Tokyo, 162-8480, Japan.
² Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama, 337-8570, Japan.
³ Translational Research Center, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan.

Abstract

Expansion of transformed cell area is regulated by the surrounding nontransformed cells. Lonidamine (LND) was recently found to regulate transformed cell area expansion through suppressing the cell motility of nontransformed cells; however, the structure-activity relationship between LND and this inhibitory activity has yet to be elucidated. We synthesized several LND derivatives and evaluated their inhibitory activity against the expansion of transformed cell area and found that the halogenation pattern on the benzene ring moiety, the carboxylic acid moiety, and the overall hydrophobicity of the molecule were correlated with inhibition activity. We also found that the localization of the tight junction protein, zonula occludens-1 (ZO-1), in nontransformed cells was significantly altered after treatment with the LND derivatives that displayed inhibitory activity. Further studies with LND derivatives and monitoring the localization of ZO-1 may help to develop more active compounds for suppressing transformed cell area expansion and lead to new anticancer treatments.

Keywords: Cancer cells; Lonidamine; Transformed cell.