Extracts from Sageretia thea reduce cell viability through inducing cyclin D1 proteasomal degradation and HO-1 expression in human colorectal cancer cells

Abstract

BackgroundSageretia thea (S. thea) has been used as the medicinal plant for treating hepatitis and fevers in Korea and China. Recently, anticancer activity of S. thea has been reported, but the potential mechanism for the anti-cancer property of S. thea is still insufficient. Thus, we evaluated whether extracts from the leaves (STL) and branches (STB) of S. thea exert anticancer activity and elucidated its potential mechanism in SW480 cells.MethodsMTT assay was performed for measuring cell viability. Western blot and RT-PCR were used for analyzing the level of protein and mRNA, respectively.ResultsTreatment of STL or STB decreased the cell viability and induced apoptosis in SW480 cells. Decreased level of cyclin D1 protein was observed in SW480 cells treated with STL or STB, but no change in cyclin D1 mRNA level was observed with the treatment of STL or STB. MG132 blocked downregulation of cyclin D1 protein by STL or STB. Thr286 phosphorylation of cyclin D1 by STL or STB occurred faster than downregulation of cyclin D1 protein in SW480 cells. When SW480 cells were transfected with T286A-cyclin D1, cyclin D1 degradation by STL or STB did not occur. Inhibition of GSK3β and cyclin D1 nuclear export attenuated STL or STB-mediated cyclin D1 degradation. In addition, STL or STB increased HO-1 expression, and the inhibition of HO-1 attenuated the induction of apoptosis by STL or STB. HO-1 expression by STL or STB resulted from Nrf2 activation through ROS-dependent p38 activation.ConclusionsThese results indicate that STL or STB may induce GSK3β-dependent cyclin D1 degradation, and increase HO-1 expression through activating Nrf2 via ROS-dependent p38 activation, which resulted in the decrease of the viability in SW480 cells. These findings suggest that STL or STB may have great potential for the development of anti-cancer drug.

Production of Secondary Metabolites from Cell Cultures of Sageretia thea (Osbeck) M.C. Johnst. Using Balloon-Type Bubble Bioreactors

“…The leaf extracts have displayed the inhibition of oxidation of low-density lipoprotein through their antioxidant and HIV type 1 protease activities [ 2 ]. Furthermore, leaf extracts have demonstrated anticancer activities against human breast cancer (MDA-MB-231) and colorectal cancer cells (SW 480) [ 9 , 10 ]. In view of the above, S. thea raw material has been used in the pharmaceutical and cosmetic industries.…”

Quantitative ethnobotanical exploration of wild medicinal plants of Arang Valley, District Bajaur, Khyber Pakhtunkhwa, Pakistan: a mountainous region of the Hindu Kush Range

“…Cardiovascular problems such as hypertension and increased cholesterol levels were commonly treated with Marrubium valgare, Melia azedarach and Sageretia thea. The medicinal herb Sageretia thea has been used in Korea and China to treat fevers and hepatitis, and researchers have also discovered that it possesses anticancer properties (Kim et al 2019). For skeletal and muscular complaints and healing of the wound, the plants like Verbascum thapsus and Rumex dentatus were administered.…”

Clinical Significance of Heme Oxygenase 1 in Tumor Progression

“…In this context, the induction of HO-1 has been proposed to increase conventional cancer therapies, and some “natural” compounds derived from plants have shown interesting properties. In colorectal cancer, it has been demonstrated that treatment with extracts from Sageretia thea , a medicinal plant used for treating hepatitis and fevers in Korea and China, decreases cell viability by inducing GSK3β-dependent cyclin D1 degradation and increasing HO-1 expression via activation of Nrf2 [ 227 ]. In addition, Ginnalin A, a polyphenolic compound isolated from red maple ( Acer rubrum ), inhibits cell viability and colony formation in colorectal cancer, inducing cell cycle arrest by activating the Nrf2/HO-1 pathway through the up-regulation of p62 and the inhibition of Keap1 [ 228 ].…”