Vitexicarpin Induces Apoptosis and Inhibits Metastatic Properties via the AKT-PRAS40 Pathway in Human Osteosarcoma

被引:2
作者
Yun, Hyung-Mun [1 ]
Kwon, Hyun Sook [2 ]
Lee, Joon Yeop [2 ]
Park, Kyung-Ran [3 ]
机构
[1] Kyung Hee Univ, Sch Dent, Dept Oral & Maxillofacial Pathol, Seoul 02447, South Korea
[2] Natl Dev Inst Korean Med, Gyongsan 38540, South Korea
[3] Korea Basic Sci Inst KBSI, Gwangju Ctr, Gwangju 61751, South Korea
关键词
AKT; apoptosis; autophagy; invasion; osteosarcoma; PRAS40; Vitexicarpin; CANCER; AUTOPHAGY; HALLMARKS; MITOCHONDRIA; NECROPTOSIS; MECHANISMS; EXPRESSION; RESISTANCE; SUBSTRATE; SURVIVIN;
D O I
10.3390/ijms25073582
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Osteosarcoma, which has poor prognosis after metastasis, is the most common type of bone cancer in children and adolescents. Therefore, plant-derived bioactive compounds are being actively developed for cancer therapy. Artemisia apiacea Hance ex Walp. is a traditional medicinal plant native to Eastern Asia, including China, Japan, and Korea. Vitexicarpin (Vitex), derived from A. apiacea, has demonstrated analgesic, anti-inflammatory, antitumour, and immunoregulatory properties; however, there are no published studies on Vitex isolated from the aerial parts of A. apiacea. Thus, this study aimed to evaluate the antitumour activity of Vitex against human osteosarcoma cells. In the present study, Vitex (>99% purity) isolated from A. apiacea induced significant cell death in human osteosarcoma MG63 cells in a dose- and time-dependent manner; cell death was mediated by apoptosis, as evidenced by the appearance of cleaved-PARP, cleaved-caspase 3, anti-apoptotic proteins (Survivin and Bcl-2), pro-apoptotic proteins (Bax), and cell cycle-related proteins (Cyclin D1, Cdk4, and Cdk6). Additionally, a human phosphokinase array proteome profiler revealed that Vitex suppressed AKT-dependent downstream kinases. Further, Vitex reduced the phosphorylation of PRAS40, which is associated with autophagy and metastasis, induced autophagosome formation, and suppressed programmed cell death and necroptosis. Furthermore, Vitex induced antimetastatic activity by suppressing the migration and invasion of MMP13, which is the primary protease that degrades type I collagen for tumour-induced osteolysis in bone tissues and preferential metastasis sites. Taken together, our results suggest that Vitex is an attractive target for treating human osteosarcoma.
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页数:15
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