Hwang, Sung Hee Lee, Byung-Hwan Kim, Hyeon-Joong Cho, Hee-Jung Shin, Ho-Chul Im, Keum-Soon Choi, Sun-Hye Shin, Tae-Joon Lee, Sang-Mok Nam, Suk Woo Kim, Hyoung-Chun Rhim, Hyewon Nah, Seung-Yeol 2024-01-20T13:04:48Z 2024-01-20T13:04:48Z 2021-09-01 2013-01 1019-6439 https://pubs.kist.re.kr/handle/201004/128512 Ginseng has been used for cancer prevention. However, little is known about its active components and the molecular mechanisms underlying its effects. Recently, we isolated a unique lysophosphatidic acid (LPA) receptor ligand, gintonin. Gintonin contains approximately 9.5% LPA, mainly LPA C-18:2. Autotaxin (ATX) is responsible for metastasis by overproducing LPA in cancers. However, LPA, particularly LPA C-18:2, is a strong negative feedback ATX inhibitor. It is unknown whether gintonin inhibits ATX activity and whether gintonin-induced ATX inhibition is coupled with antimetastatic activity. In this study, we examined whether gintonin and LPA C-18:2 inhibit ATX activity and metastasis-related cellular activities in melanoma cells. We found that gintonin and LPA C-18:2 inhibited the purified and secreted ATX activity from melanoma cells in a concentration-dependent manner. Gintonin also inhibited cell migration with a minimal inhibition of cell growth. The oral administration of gintonin or LPA C-18:2 inhibited lung metastasis induced by tail-vein inoculations of melanoma cells. Moreover, the oral administration of gintonin significantly suppressed the tumor growth induced by subcutaneous grafts of melanoma cells. A histological analysis showed that the oral administration of gintonin reduced tumor necrosis, the pleomorphism of tumor cells, tumor cell mitosis and angiogenesis. The present study demonstrates that the gintonin-induced inhibition of ATX activity may be the molecular basis of ginseng-induced antimetastatic and antitumor activities. English SPANDIDOS PUBL LTD LYSOPHOSPHOLIPASE-D ACTIVITY MIGRATION IN-VITRO LYSOPHOSPHATIDIC ACID BREAST-CANCER ANTICANCER ACTIVITY RECEPTOR GROWTH PROTEIN LPA IDENTIFICATION Suppression of metastasis of intravenously-inoculated B16/F10 melanoma cells by the novel ginseng-derived ingredient, gintonin: Involvement of autotaxin inhibition Article 10.3892/ijo.2012.1709 1 INTERNATIONAL JOURNAL OF ONCOLOGY, v.42, no.1, pp.317 - 326 INTERNATIONAL JOURNAL OF ONCOLOGY 42 1 317 326 scie scopus 000312566900036 2-s2.0-84873673939 Oncology Oncology Article LYSOPHOSPHOLIPASE-D ACTIVITY MIGRATION IN-VITRO LYSOPHOSPHATIDIC ACID BREAST-CANCER ANTICANCER ACTIVITY RECEPTOR GROWTH PROTEIN LPA IDENTIFICATION Panax ginseng gintonin lysophosphatidic acid autotaxin metastasis anti-metastasis B16/F10 melanoma cells