Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways

Tsung-Chang Tsai; Wen-Tung Wu; Jen-Jie Lin; Jui-Hsin Su; Yu-Jen Wu

doi:10.1155/2022/4416611

Stellettin B Isolated from Stelletta Sp. Reduces Migration and Invasion of Hepatocellular Carcinoma Cells through Reducing Activation of the MAPKs and FAK/PI3K/AKT/mTOR Signaling Pathways

Int J Cell Biol. 2022 Nov 29:2022:4416611. doi: 10.1155/2022/4416611. eCollection 2022.

Authors

Tsung-Chang Tsai^{1

2}, Wen-Tung Wu³, Jen-Jie Lin^{3

4}, Jui-Hsin Su^{5

6}, Yu-Jen Wu^{3

4}

Affiliations

¹ Department of Nephrology, Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung 92842, Taiwan.
² Department of Nursing, Meiho University, Pingtung 91202, Taiwan.
³ Department of Food Science and Nutrition, Meiho University, Pingtung 91202, Taiwan.
⁴ Yu Jun Biotechnology Co., Ltd., Kaohsiung 81363, Taiwan.
⁵ National Museum of Marine Biology & Aquarium, Pingtung 94450, Taiwan.
⁶ Frontier Center for Ocean Science and Technology, National Sun Yat-sen University, Kaohsiung 80424, Taiwan.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors, and there is currently a lack of effective treatment options to control the metastasis. This study was performed to examine the mechanisms of the migration and invasion characteristics of HCC, with the aim of reducing metastasis by inhibiting cancer cell migration and invasion. In this study, we used Stellettin B, an active compound isolated from Stelletta sponges, as the experimental drug and evaluated its inhibition effects on cell migration and invasion in human hepatoma cells (HA22T and HepG2). MTT assay, gelatin zymography, and western blotting were employed. The results showed that Stellettin B significantly inhibited the protein expressions of MMP-2, MMP-9, and uPA, while upregulating the protein expressions of TIMP-1 and TIMP-2. The expressions of p-FAK, p-PI3K, p-AKT, p-mTOR, and MAPKs (p-JNK, p-JUN, p-MAPKp38, and p-ERK) were decreased with increasing concentrations of Stellettin B. Our results suggest that Stellettin B-dependent downregulation of MMP-2 and MMP-9 activities could be mediated by FAK/PI3K/AKT/mTOR and MAPKs signaling pathways in HA22T and HepG2 cells, preventing HCC invasion and migration.