Anti‑proliferative effect of ridaifen‑B on hepatoma cells

Hasegawa,Go; Akatsuka,Kotomi; Hiruma,Keita; Suda,Kayako; Yokoe,Yumiko; Mizusawa,Akihito; Ota,Nozomi; Shibata,Natsumi; Tsuchiya,Kaho; Hayashi,Moyuru; Shiina,Isamu; Shimonaka,Motoyuki

doi:10.3892/br.2018.1112

Anti‑proliferative effect of ridaifen‑B on hepatoma cells

Authors:
- Go Hasegawa
- Kotomi Akatsuka
- Keita Hiruma
- Kayako Suda
- Yumiko Yokoe
- Akihito Mizusawa
- Nozomi Ota
- Natsumi Shibata
- Kaho Tsuchiya
- Moyuru Hayashi
- Isamu Shiina
- Motoyuki Shimonaka
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Affiliations: Department of Chemistry, Faculty of Science, Tokyo University of Science, Tokyo 162‑8601, Japan, Department of Chemistry, Graduate School of Science, Tokyo University of Science, Tokyo 162‑8601, Japan, Department of Chemical Sciences and Technology, Graduate School of Chemical Sciences and Technology, Tokyo University of Science, Tokyo 162‑8601, Japan, Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Tokyo 162‑8601, Japan
Published online on: June 13, 2018 https://doi.org/10.3892/br.2018.1112
Pages: 175-180

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Abstract

Ridaifens (RIDs), a novel series of tamoxifen derivatives, exhibit a potent growth‑inhibitory effect against numerous tumor cells regardless of the expression of estrogen receptors, and are thus promising candidates as novel anti‑tumor drugs. RID‑B is a first generation RIDs, and inhibits the proliferation of several tumor cell lines. However, the potentially growth inhibitory effect of RID‑B against hepatoma cells, and the detailed mechanism underlying RID‑B‑mediated tumor cell death remain to be elucidated. The purpose of the current study was to evaluate the anti‑proliferative effect of RID‑B against hepatoma cells. The anti‑proliferative effect of RID‑B against human hepatoma Huh‑7 cells was investigated by cell proliferation assay using WST‑1 reagent, and caspase‑3 activity was evaluated by using specific fluorescent substrate. In addition, DNA fragmentation in Huh‑7 cells induced by RID‑B was estimated by terminal deoxynucleotidyl transferase dUTP nick‑end labelling assay, and binding of RID‑B to double‑stranded DNA was confirmed by mass spectrometry. RID‑B (0.5, 1 and 2 µM) inhibited the growth of Huh‑7 cells, seemingly dose‑dependently, but did not inhibit the growth of normal primary rat hepatocytes in the same concentration range. Furthermore, the caspase‑3 activity of Huh‑7 cells was increased by RID‑B (0.5 and 5 µM), and the anti‑proliferative effect of RID‑B (1 µM) on Huh‑7 cells was partially suppressed by the addition of the caspase inhibitor, Z‑VAD‑FMK. Additionally, RID‑B (10 µM) directly bound to double‑stranded DNA, and the addition of DNA suppressed RID‑B‑mediated cell growth inhibition and DNA fragmentation in Huh‑7 cells. From these data, it may be concluded that RID‑B inhibited cell growth and induced apoptosis via activating caspase‑3 and binding to DNA directly, leading to DNA fragmentation in hepatoma cells.

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