Issue |
BioMedicine
Volume 7, Number 2, June 2017
|
|
---|---|---|
Article Number | 12 | |
Number of page(s) | 12 | |
DOI | https://doi.org/10.1051/bmdcn/2017070205 | |
Published online | 14 June 2017 |
Original article
YC-1 induces G0/G1 phase arrest and mitochondria-dependent apoptosis in cisplatin-resistant human oral cancer CAR cells
1
Department of Biochemistry, China Medical University, Taichung
404, Taiwan
2
Department of Physiology, China Medical University, Taichung
404, Taiwan
3
Department of Medical Research, China Medical University Hospital, China Medical University, Taichung
404, Taiwan
4
Chinese Medicinal Research and Development Center, China Medical University Hospital, China Medical University, Taichung
404, Taiwan
5
School of Pharmacy, China Medical University, Taichung
404, Taiwan
6
Department of Pharmacy, Buddhist Tzu Chi General Hospital, Hualien
970, Taiwan
7
Yung-Shin Pharmaceutical Industry Co., Ltd., Tachia, Taichung
437, Taiwan
8
Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung
404, Taiwan
9
School of Chinese Medicine, China Medical University, Taichung
404, Taiwan
10
Department of Medical Genetics, China Medical University Hospital, Taichung
404, Taiwan
* Corresponding author. Department of Medical Research, China Medical University Hospital, China Medical University, No. 2, Yuh-Der Road, Taichung 40447, Taiwan. E-mail addresses: jaisingyang@gmail.com (J.-S. Yang), d0704@mail.cmuh.org.tw (F.-J. Tsai).
Received:
10
April
2017
Accepted:
2
May
2017
Oral cancer is a serious and fatal disease. Cisplatin is the first line of chemotherapeutic agent for oral cancer therapy. However, the development of drug resistance and severe side effects cause tremendous problems clinically. In this study, we investigated the pharmacologic mechanisms of YC-1 on cisplatin-resistant human oral cancer cell line, CAR. Our results indicated that YC-1 induced a concentration-dependent and time-dependent decrease in viability of CAR cells analyzed by MTT assay. Real-time image analysis of CAR cells by IncuCyte™ Kinetic Live Cell Imaging System demonstrated that YC-1 inhibited cell proliferation and reduced cell confluence in a time-dependent manner. Results from flow cytometric analysis revealed that YC-1 promoted G0/G1 phase arrest and provoked apoptosis in CAR cells. The effects of cell cycle arrest by YC-1 were further supported by up-regulation of p21 and down-regulation of cyclin A, D, E and CDK2 protein levels. TUNEL staining showed that YC-1 caused DNA fragmentation, a late stage feature of apoptosis. In addition, YC-1 increased the activities of caspase-9 and caspase-3, disrupted the mitochondrial membrane potential (AYm) and stimulated ROS production in CAR cells. The protein levels of cytochrome c, Bax and Bak were elevated while Bcl-2 protein expression was attenuated in YC-1-treated CAR cells. In summary, YC-1 suppressed the viability of cisplatin-resistant CAR cells through inhibiting cell proliferation, arresting cell cycle at G0/G1 phase and triggering mitochondria-mediated apoptosis. Our results provide evidences to support the potentially therapeutic application of YC-1 on fighting against drug resistant oral cancer in the future.
Key words: YC-1 / G0/G1 phase arrest / mitochondria / Apoptosis / CAR cells
© Author(s) 2017. This article is published with open access by China Medical University
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