Anti-proliferative activity of A. Oxyphylla and its bioactive constituent nootkatone in colorectal cancer cells

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.

Impairment of Glucose Metabolism and Suppression of Stemness in MCF-7/SC Human Breast Cancer Stem Cells by Nootkatone

“…Incubation with nootkatone has been reported to induce AMPK activation, resulting in suppression of the Erk and Akt signaling pathways in A549 cells. Moreover, nootkatone treatment inhibited cell proliferation in colorectal cancer cells, as evidenced by a reduction in cyclin D1 [ 19 , 20 ]. On the other hand, nootkatone has also been well characterized as an AMPK activator in vitro and in vivo.…”

“…Nootkatone is a natural chemical produced in grapefruit that reduces diet-induced obesity and stimulates energy metabolism by activating AMPK [ 17 , 18 ]. Nootkatone may also act as an anticancer agent in lung and colorectal tumors [ 19 , 20 ]. In this study, we investigated the hypothesis that regulation of glucose metabolism by AMPK activation could be the mechanism underlying the effect of nootkatone on BCSCs.…”

Nardosinone Alleviates Parkinson’s Disease Symptoms in Mice by Regulating Dopamine D2 Receptor

“…A literature search was conducted on these chemical components. Dehydrocostus lactone has anticancer [ 34 ] and antioxidative stress [ 35 ] effects; nootkatone has anti-inflammatory [ 36 ], antitumor [ 37 ], and anti-Alzheimer's [ 38 ] effects; nardosinone is a major active component of nardostachys. It has antianxiety, antidepressant, and neuroprotective effects.…”

Quercetin Induces Anticancer Activity by Upregulating Pro-NAG-1/GDF15 in Differentiated Thyroid Cancer Cells

“…Thus, two forms of NAG-1 exhibit different activities in cancer; the pro-form shows anticancer activity, whereas the mature form shows pro-cancer activity during tumorigenesis [ 14 ]. In addition, the level of pro-NAG-1 was increased by several phytochemicals and plant extracts [ 15 , 16 , 17 , 18 , 19 ], providing a potential biomarker for anticancer compounds.…”