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Toxins 2016, 8(11), 319; doi:10.3390/toxins8110319

Tenuifolide B from Cinnamomum tenuifolium Stem Selectively Inhibits Proliferation of Oral Cancer Cells via Apoptosis, ROS Generation, Mitochondrial Depolarization, and DNA Damage

1
Department of Nutrition and Health Sciences, School of Medical and Health Sciences, Fooyin University, Kaohsiung 83102, Taiwan
2
Department of Oral and Maxillofacial Surgery Chi-Mei Medical Center, Tainan 71004, Taiwan
3
School of Dentistry, Taipei Medical University, Taipei 11031, Taiwan
4
Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
5
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
6
Department of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
7
Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung 80708, Taiwan
8
Department of Radiation Oncology, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung 80145, Taiwan
9
Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung 80424, Taiwan
10
Institute of Medical Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
11
Cancer Center, Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
12
Center for Research Resources and Development of Kaohsiung Medical University, Kaohsiung 80708, Taiwan
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Academic Editor: Carmela Fimognari
Received: 15 January 2016 / Revised: 11 October 2016 / Accepted: 19 October 2016 / Published: 5 November 2016
(This article belongs to the Special Issue Dietary and Non-Dietary Phytochemicals and Cancer)
View Full-Text   |   Download PDF [3656 KB, uploaded 5 November 2016]   |  

Abstract

The development of drugs that selectively kill oral cancer cells but are less harmful to normal cells still provide several challenges. In this study, the antioral cancer effects of tenuifolide B (TFB), extracted from the stem of the plant Cinnamomum tenuifolium are evaluated in terms of their effects on cancer cell viability, cell cycle analysis, apoptosis, oxidative stress, and DNA damage. Cell viability of oral cancer cells (Ca9-22 and CAL 27) was found to be significantly inhibited by TFB in a dose-responsive manner in terms of ATP assay, yielding IC50 = 4.67 and 7.05 μM (24 h), but are less lethal to normal oral cells (HGF-1). Dose-responsive increases in subG1 populations as well as the intensities of flow cytometry-based annexin V/propidium iodide (PI) analysis and pancaspase activity suggested that apoptosis was inducible by TFB in these two types of oral cancer cells. Pretreatment with the apoptosis inhibitor (Z-VAD-FMK) reduced the annexin V intensity of these two TFB-treated oral cancer cells, suggesting that TFB induced apoptosis-mediated cell death to oral cancer cells. Cleaved-poly (ADP-ribose) polymerase (PARP) and cleaved-caspases 3, 8, and 9 were upregulated in these two TFB-treated oral cancer cells over time but less harmful for normal oral HGF-1 cells. Dose-responsive and time-dependent increases in reactive oxygen species (ROS) and decreases in mitochondrial membrane potential (MitoMP) in these two TFB-treated oral cancer cells suggest that TFB may generate oxidative stress as measured by flow cytometry. N-acetylcysteine (NAC) pretreatment reduced the TFB-induced ROS generation and further validated that ROS was relevant to TFB-induced cell death. Both flow cytometry and Western blotting demonstrated that the DNA double strand marker γH2AX dose-responsively increased in TFB-treated Ca9-22 cells and time-dependently increased in two TFB-treated oral cancer cells. Taken together, we infer that TFB can selectively inhibit cell proliferation of oral cancer cells through apoptosis, ROS generation, mitochondrial membrane depolarization, and DNA damage. View Full-Text
Keywords: selective killing; oral cancer; natural product; apoptosis; ROS; DNA damage selective killing; oral cancer; natural product; apoptosis; ROS; DNA damage
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MDPI and ACS Style

Chen, C.-Y.; Yen, C.-Y.; Wang, H.-R.; Yang, H.-P.; Tang, J.-Y.; Huang, H.-W.; Hsu, S.-H.; Chang, H.-W. Tenuifolide B from Cinnamomum tenuifolium Stem Selectively Inhibits Proliferation of Oral Cancer Cells via Apoptosis, ROS Generation, Mitochondrial Depolarization, and DNA Damage. Toxins 2016, 8, 319.

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