title: The Inhibitory Effect of Abietic Acid on Melanoma Cancer Metastasis and Invasiveness In Vitro and In Vivo.
abstract: Melanoma cell metastasis is the primary cause of patient death. Thus, various treatment strategies have been developed to prevent metastasis. Abietic acid (AA) is an organic compound commonly found in trees. This study is aimed to investigate the antimetastatic activity of AA in B16F10-xenografted C57BL/6 mice and assess the anticancer activity of AA in combination with Taxol in melanoma cells. AA effectively reduced the formation of lung metastases by approximately 92.8%. AA treatment inhibited migratory potential (p < 0.001), invasion (p < 0.001), and motility (p < 0.001) of highly metastatic B16F10 melanoma cells in vitro. Zymography revealed that AA reduced the proteinase activities of matrix metalloproteinase-2 and urokinase-type plasminogen activator. Molecular analyses showed that AA reduced Akt phosphorylation and activating protein-1 DNA-binding activity by Western blot and electrophoretic mobility shift assay (EMSA), respectively. In summary, AA effectively inhibited B16F10 lung metastasis, and 50[Formula: see text][Formula: see text]M AA did not affect the viability of B16F10 cells. AA improved the efficacy of Taxol and demonstrated strong anticancer activity on melanoma cells. These results suggested that AA could be used as an antimetastatic agent or as an adjuvant for anticancer therapy.
authors.affiliation: * Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.|† Institute of Biochemistry, Microbiology and Immunology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.affiliation: ‡ Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.affiliation: † Institute of Biochemistry, Microbiology and Immunology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Yi-Hsien
authors.initials: YH
authors.lastname: Hsieh
authors.affiliation: † Institute of Biochemistry, Microbiology and Immunology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Chia-Hung
authors.initials: CH
authors.lastname: Hung
authors.affiliation: § Institute and Department of Food Science, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.affiliation: † Institute of Biochemistry, Microbiology and Immunology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Sheng-Han
authors.initials: SH
authors.lastname: Yang
authors.affiliation: * Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan.|† Institute of Biochemistry, Microbiology and Immunology, Central Taiwan University of Science and Technology, Taichung, Taiwan.
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
mesh_terms: D045784:Abietanes / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D010447:Peptide Hydrolases / Q000378:metabolism; D008517:Phytotherapy; D012867:Skin / Q000166:cytology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D014197:Trees / Q000737:chemistry; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D045784:Abietanes; D000972:Antineoplastic Agents, Phytogenic; D010447:Peptide Hydrolases; D014568:Urokinase-Type Plasminogen Activator; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2; C023710:abietic acid
keywords: Abietic Acid; Matrix Metalloproteinase-2; Melanoma; Metastasis; Urokinase-Type Plasminogen Activator