Taiwanin E Induces Cell Cycle Arrest and Apoptosis in Arecoline/4-NQO-Induced Oral Cancer Cells Through Modulation of the ERK Signaling Pathway

Shih-Hao Wang; Hsi-Chin Wu; Khan Farheen Badrealam; Yueh-Hsiung Kuo; Yun-Peng Chao; Hsi-Hsien Hsu; Da-Tian Bau; Vijaya Padma Viswanadha; Yi-Hui Chen; Pei-Jei Lio; Chung-Jen Chiang; Chih-Yang Huang

doi:10.3389/fonc.2019.01309

Taiwanin E Induces Cell Cycle Arrest and Apoptosis in Arecoline/4-NQO-Induced Oral Cancer Cells Through Modulation of the ERK Signaling Pathway

Front Oncol. 2019 Dec 17:9:1309. doi: 10.3389/fonc.2019.01309. eCollection 2019.

Authors

Shih-Hao Wang^{1

2}, Hsi-Chin Wu³, Khan Farheen Badrealam⁴, Yueh-Hsiung Kuo^{2

5

6}, Yun-Peng Chao⁷, Hsi-Hsien Hsu^{8

9}, Da-Tian Bau⁴, Vijaya Padma Viswanadha¹⁰, Yi-Hui Chen¹¹, Pei-Jei Lio¹², Chung-Jen Chiang¹², Chih-Yang Huang^{2

4

13

14

15}

Affiliations

¹ Department of Otolaryngology, Ditmanson Medical Foundation, Chiayi Christian Hospital, Chiayi, Taiwan.
² Department of Biotechnology, Asia University, Taichung, Taiwan.
³ School of Medicine, China Medical University, Taichung, Taiwan.
⁴ Graduate Institute of Biomedicine, China Medical University and Hospital, Taichung, Taiwan.
⁵ Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
⁶ Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
⁷ Department of Chemical Engineering, Feng Chia University, Taichung, Taiwan.
⁸ Division of Colorectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan.
⁹ Mackay Medicine, Nursing and Management College, Taipei, Taiwan.
¹⁰ Department of Biotechnology, Bharathiar University, Coimbatore, India.
¹¹ Department of M-Commerce and Multimedia Applications, Asia University, Taichung, Taiwan.
¹² Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung, Taiwan.
¹³ Cardiovascular and Mitochondria Related Diseases Research Center, Hualien Tzu Chi Hospital, Hualien, Taiwan.
¹⁴ Center of General Education, Buddhist Tzu Chi Medical Foundation, Tzu Chi University of Science and Technology, Hualien, Taiwan.
¹⁵ Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.

Abstract

Taiwanin E is a bioactive compound extracted from Taiwania cryptomerioides Hayata. In this research endeavor, we studied the anti-cancer effect of Taiwanin E against arecoline and 4-nitroquinoline-1-oxide-induced oral squamous cancer cells (OSCC), and elucidated the underlying intricacies. OSCC were treated with Taiwanin E and analyzed through MTT assay, Flow cytometry, TUNEL assay, and Western blotting for their efficacy against OSCC. Interestingly, it was found that Taiwanin E significantly attenuated the cell viability of oral cancer cells (T28); however, no significant cytotoxic effects were found for normal oral cells (N28). Further, Flow cytometry analysis showed that Taiwanin E induced G1cell cycle arrest in T28 oral cancer cells and Western blot analysis suggested that Taiwanin E considerably downregulated cell cycle regulatory proteins and activated p53, p21, and p27 proteins. Further, TUNEL and Western blot studies instigated that it induced cellular apoptosis and attenuated the p-PI3K/p-Akt survival mechanism in T28 oral cancer cells seemingly through modulation of the ERK signaling cascade. Collectively, the present study highlights the prospective therapeutic efficacy of Taiwanin E against arecoline and 4-nitroquinoline-1-oxide-induced oral cancer.

Keywords: Taiwanin E; apoptosis; cell cycle arrest; oral cancer; therapeutics.