Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells
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RESEARCH ARTICLE
Open Access
Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells Eunsu Yoo1, Jaehak Lee1, Pattawika Lertpatipanpong1, Junsun Ryu2, Chong-Tai Kim3, Eul-Yong Park3 and Seung Joon Baek1*
Abstract Background: A. oxyphylla extract is known to possess a wide range of pharmacological activites. However, the molecular mechanism of A. oxyphylla and its bioactive compound nootkatone in colorectal cancer is unknown. Methods: Our study aims to examine the role of A. oxyphylla and its bioactive compound nootkatone, in tumor suppression using several in vitro assays. Results: Both A. oxyphylla extract and nootkatone exhibited antiproliferative activity in colorectal cancer cells. A. oxyphylla displayed antioxidant activity in colorectal cancer cells, likely mediated via induction of HO-1. Furthermore, expression of pro-apoptotic protein NAG-1 and cell proliferative protein cyclin D1 were increased and decreased respectively in the presence of A. oxyphylla. When examined for anticancer activity, nootkatone treatment resulted in the reduction of colony and spheroid formation. Correspondingly, nootkatone also led to increased NAG-1 expression and decreased cyclin D1 expression. The mechanism by which nootkatone suppresses cyclin D1 involves protein level regulation, whereas nootkatone increases NAG-1 expression at the transcriptional level. In addition to having PPARγ binding activity, nootkatone also increases EGR-1 expression which ultimately results in enhanced NAG-1 promoter activity. Conclusion: In summary, our findings suggest that nootkatone is an anti-tumorigenic compound harboring antiproliferative and pro-apoptotic activity. Keywords: Nootkatone, NAG-1, Cyclin D1, A. oxyphylla
Background Alpinia oxyphylla belongs to the Zingiberaceae family and is widely cultivated in Asia as one of the most frequently used plant extracts in oriental medicine. The most well-known medicinal effect of A. oxyphylla includes enhancing the internal and astringent activities of the kidney and spleen [1]. Recent studies have shown * Correspondence: [email protected] 1 Department of Veterinary Medicine, College of Veterinary Medicine and Research Institute for Veterinary Science, Seoul National University, Seoul 08826, South Korea Full list of author information is available at the end of the article
that A. oxyphylla possesses a wide range of pharmacological activities, such as anti-diabetes [2], anti-fibrosis [3], anti-diarrheal [4], and anti-cancer [5]. A. oxyphylla contains various chemical constituents, including essential oils, sesquiterpenes, flavones, diarylheptanoids, glycosides and steroids. Amongst them, nootkatone is one of the more abundant components [6]. Nootkatone has also been identified as the main fragrant component of grapefruit with a wide range of beneficial effects including anti-inflammation activities [7], AMPK activation [8] and neuroprotective effects [9]. Other bioactive compounds in A. oxyphylla,
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