Sea cucumber extract TBL‐12 inhibits the proliferation, migration, and invasion of human prostate cancer cells through the p38 mitogen‐activated protein kinase and intrinsic caspase apoptosis pathway

• Published in: The Prostate 2019-06, Vol.79 (8), p.826-839
• Main Authors: Yuan, Lei, Huang, Xubin, Zhou, Kai, Zhu, Xun, Huang, Bin, Qiu, Shaopeng, Cao, Kaiyuan, Xu, Lin
• Format: Article
• Language: English
• Subjects: Angiogenesis; Angiogenic Proteins - metabolism; Angiogenin; Angiopoietin; Animals; Antioxidants; Antitumor activity; Apoptosis; Apoptosis - drug effects; Autocrine signalling; Caspase; Caspase 7 - metabolism; Caspase 9 - metabolism; Cell Line, Tumor; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Colonies; Down-Regulation - drug effects; Enzymatic activity; Flow cytometry; Gelatin; Growth factors; Humans; Invasiveness; Kinases; Male; MAP kinase; MAP Kinase Signaling System - drug effects; Matrix Metalloproteinase 2 - metabolism; Matrix Metalloproteinase 9 - metabolism; matrix metalloproteinases; Metastases; Mice; Neoplasm Invasiveness; p38 Mitogen-Activated Protein Kinases - metabolism; PC-3 Cells; Polymerase chain reaction; Prostate cancer; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; Protein kinase; sea cucumber extract; Sea Cucumbers - chemistry; Secretion; Tissue Extracts - pharmacology; Tumor cell lines; tumor metastasis; Vascular endothelial growth factor; Xenograft Model Antitumor Assays; Xenografts
• ISSN: 0270-4137; 1097-0045
• DOI: 10.1002/pros.23788

Background Sea cucumber is a kind of nutritious echinoderm that has multiple biological activities, including antioxidant, antibacterial, and antitumor activities. However, there is no extensive study on the antitumor effect of sea cucumber extract on prostate cancer (PCa). TBL‐12 is a new sea cucumber extract. In this study, we investigated the in vivo anti‐PCa effect of TBL‐12 and its in vitro effects on the proliferation, apoptosis, migration, and invasion of the human PCa cell lines LNCaP, 22RV1, PC‐3, and DU145, and evaluated its possible mechanisms. Methods Cell proliferation was analyzed by cell counting kit‐8 and colony formation assays. Scratch migration assay and transwell invasiveness assay were used to observe TBL‐12 effect on the migration and invasion of PCa cells. Matrix metalloproteinase 2 (MMP‐2) and MMP‐9 expression and enzymatic activity was determined by Western blot analysis, quantitative reverse‐transcription polymerase chain reaction, and gelatin zymography. Apoptosis level was detected by flow cytometry analysis. Western blot analysis was used to analyze p38 mitogen‐activated protein kinase (MAPK) and apoptosis pathways. Angiogenic array analysis was used to explore autocrine and paracrine growth factors in PCa cell lines. Xenograft tumor model was built to observe the in vivo anticancer effect. Results TBL‐12 could significantly inhibit tumor growth in xenograft PCa mice in vivo, and dramatically inhibit the proliferation, colony formation, migration, and invasiveness of PCa cells in vitro (P