CCL113, a novel sulfonamide, induces selective mitotic arrest and apoptosis in HeLa and HepG2 cells

Yi,Ruirong; Ohno,Yoshifumi; Tian,Zheng; Guo,Shuhan; Chen,Weiwei; Ma,Xue; Win,Nan Nwe; Li,Qisen; Vahed,Majid; Saito,Kengo; Nakamoto,Shingo; Suganami,Akiko; Isegawa,Naohisa; Yoshida,Keisuke; Harada,Shinji; Tamura,Yutaka; Nishida,Atsushi; Shirasawa,Hiroshi

doi:10.3892/or.2020.7805

CCL113, a novel sulfonamide, induces selective mitotic arrest and apoptosis in HeLa and HepG2 cells

Authors:
- Ruirong Yi
- Yoshifumi Ohno
- Zheng Tian
- Shuhan Guo
- Weiwei Chen
- Xue Ma
- Nan Nwe Win
- Qisen Li
- Majid Vahed
- Kengo Saito
- Shingo Nakamoto
- Akiko Suganami
- Naohisa Isegawa
- Keisuke Yoshida
- Shinji Harada
- Yutaka Tamura
- Atsushi Nishida
- Hiroshi Shirasawa
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Affiliations: Department of Molecular Virology, Graduate School of Medicine, Chiba University, Chuo‑ku, Chiba 260‑8670, Japan, Graduate School of Pharmaceutical Sciences, Chiba University, Chuo‑ku, Chiba 260‑8670, Japan, Molecular Chirality Research Center, Chiba University, Chuo‑ku, Chiba 260‑8670, Japan, Department of Bioinformatics, Graduate School of Medicine, Chiba University, Chuo‑ku, Chiba 260‑8670, Japan
Published online on: October 13, 2020 https://doi.org/10.3892/or.2020.7805
Pages: 2770-2782

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Abstract

Targeting cell‑cycle regulation to hinder cancer cell proliferation is a promising anticancer strategy. The present study investigated the effects of a novel sulfonamide, CCL113, on cell cycle progression in cancer cell lines (HeLa and HepG2), a noncancerous cell line (Vero) and a normal human fibroblast cell line (TIG‑1‑20). The present results showed that treatment with CCL113 significantly decreased the viability of the cancer cells. FACS analyses showed that CCL113 treatment increased the proportion of cancerous and noncancerous cells in the G2/M phase. Analyses of cell cycle regulatory proteins showed that CCL113 treatment inhibited the activity of CDK1 in HeLa cells, possibly due to the decrease in the level of Cdc25B/C proteins and arrest in the M phase. Using time‑lapse imaging‑assisted analyses of HeLa and Vero cells expressing fluorescent ubiquitination‑based cell cycle indicator (FUCCI), it was observed that CCL113 treatment led to a prolonged G2 phase at the G2/M checkpoint and arrest in the M phase in both cell lines. This possibly activated the DNA damage response in noncancerous cells, while inducing mitotic arrest leading to apoptosis in the cancer cells. The results of molecular docking studies suggested that CCL113 might have the potential to bind to the taxol‑binding site on β‑tubulin. In conclusion, CCL113 holds potential as a reliable anticancer drug due to its ability to induce mitotic arrest followed by apoptosis of cancer cells and to activate the DNA damage response in noncancerous cells, thereby facilitating exit from the cell cycle.

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