Pro‑apoptotic effect of the novel benzylidene derivative MHY695 in human colon cancer cells

Heo,Gwangbeom; Kang,Dongwan; Park,Chaeun; Kim,Su  Jin; Choo,Jieun; Lee,Yunna; Yoo,Jin‑Wook; Jung,Yunjin; Lee,Jaewon; Kim,Nam  Deuk; Chung,Hae  Young; Moon,Hyung  Ryong; Im,Eunok

doi:10.3892/ol.2019.10664

Pro‑apoptotic effect of the novel benzylidene derivative MHY695 in human colon cancer cells

Authors:
- Gwangbeom Heo
- Dongwan Kang
- Chaeun Park
- Su Jin Kim
- Jieun Choo
- Yunna Lee
- Jin‑Wook Yoo
- Yunjin Jung
- Jaewon Lee
- Nam Deuk Kim
- Hae Young Chung
- Hyung Ryong Moon
- Eunok Im
View Affiliations

Affiliations: College of Pharmacy, Pusan National University, Geumjeong‑gu, Busan 46241, Republic of Korea
Published online on: July 25, 2019 https://doi.org/10.3892/ol.2019.10664
Pages: 3256-3264
Copyright: © Heo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The induction of apoptosis is a useful strategy in anti‑cancer research. Various Moon Hyung Yang (MHY) compounds have been developed as novel anti‑cancer drug candidates; in the present study, the pro‑apoptotic effects of (Z)‑5‑(3‑ethoxy‑4‑hydroxybenzylidene)‑2‑thioxothiazolidin‑4‑one (MHY695) on HCT116 human colon cancer cells were assessed. MTT assays were performed to investigate the dose‑dependent cytotoxic effects of MHY695 on HCT116 cells. Immunofluorescence staining and flow cytometry analyses were performed to identify apoptotic cell death, and western blot analysis was used to investigate the apoptotic‑signaling pathways. A mouse xenograft model was also used to determine the effects of MHY695 in vivo. MHY695 decreased the viability of HCT116 cells and induced apoptotic cytotoxicity. The apoptotic mechanisms induced by MHY695 involved the dephosphorylation of Bcl‑2‑associated agonist of cell death protein following protein kinase B inactivation, induced myeloid leukaemia cell differentiation protein and BH3‑interacting domain death agonist truncation, caspase‑3 and ‑9 activation and poly (ADP‑ribose) polymerase cleavage. In addition, MHY695 significantly suppressed tumor growth in the mouse xenograft model, compared with the vehicle control. Notably, MHY695 exhibited potent anti‑cancer effects in four different types of human colon cancer cell line, including Caco‑2, DLD‑1, HT‑29 and HCT116. Additionally, MHY695 showed reduced cytotoxicity in NCM460, normal colonic epithelial cells. Furthermore, MHY‑induced cytotoxicity in colon cancer cells was independent of the tumor suppressor protein p53. Collectively, these observations suggested that MHY695 may be a novel drug for the treatment of colon cancer.

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