title: Andrographis paniculata elicits anti-invasion activities by suppressing TM4SF3 gene expression and by anoikis-sensitization in esophageal cancer cells.
abstract: Esophageal cancer is the sixth most common cancer in male causing death worldwide. It is usually diagnosed at advanced stage with high postoperative recurrence and systemic metastasis, which leads to poor prognosis. The potential inhibitory effect of herbal medicines on metastasis of esophageal cancer has drawn researchers' great attention. In the present study, the anti-invasion activities of Andrographis paniculata (AP) have been evaluated in two esophageal cancer cell lines, EC-109 and KYSE-520, as well as human microvascular endothelial cells (HMEC-1). The anti-tumor and anti-metastatic activities of AP were also evaluated in human esophageal xenograft-bearing mouse models. Our results demonstrated for the first time that aqueous extract of AP inhibited the motility and invasion of esophageal cancer cells, which is the initial step of metastasis, without cytotoxicity. Anoikis resistance has also been reversed in AP-treated cancer cells. Besides, the expression of metastasis-related gene TM4SF3 in EC-109 cells was significantly decreased in AP extract-treated cells in a concentration-dependent manner. Furthermore, the anti-tumor and anti-metastatic efficacies in subcutaneous and intraperitoneal esophageal xenograft-bearing mice were demonstrated after oral administration of AP aqueous extract for 3 weeks. Last but not least, the active component, isoandrographolide, responsible for the anti-migratory activity was firstly revealed here. In conclusion, the AP aqueous extract exerted inhibitory activities on the migration and anoikis resistance of esophageal cancer cells EC-109 and KYSE-520, as well as suppressed the proliferation and motility of endothelial cells. Combining the mentioned effects may account for the anti-tumor and anti-metastasis effects of AP aqueous extract in xenograft-bearing mice. The findings in the present study further enhance the understanding of the therapeutic mechanisms of the herb AP, which may lead to clinical applications.
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong KongHong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong KongHong Kong.
authors.forename: Grace Gar-Lee
authors.initials: GG
authors.lastname: Yue
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong KongHong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong KongHong Kong.
authors.forename: Julia Kin-Ming
authors.initials: JK
authors.lastname: Lee
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong Hong Kong.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong KongHong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong KongHong Kong.
authors.forename: Kar-Man
authors.initials: KM
authors.lastname: Chan
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong KongHong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong KongHong Kong.
authors.forename: Eric Chun-Wai
authors.initials: EC
authors.lastname: Wong
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong KongHong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong KongHong Kong.
authors.forename: Judy Yuet-Wah
authors.initials: JY
authors.lastname: Chan
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong KongHong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong KongHong Kong; School of Biomedical Sciences, The Chinese University of Hong KongHong Kong.
authors.forename: Kwok-Pui
authors.initials: KP
authors.lastname: Fung
authors.affiliation: Department of Pharmacology and Pharmacy, The University of Hong KongHong Kong; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong KongHong Kong.
authors.forename: Vivian Wai Yan
authors.initials: VW
authors.lastname: Lui
authors.affiliation: Department of Surgery, The Chinese University of Hong Kong Hong Kong.
authors.forename: Philip Wai-Yan
authors.initials: PW
authors.lastname: Chiu
authors.affiliation: Institute of Chinese Medicine, The Chinese University of Hong KongHong Kong; State Key Laboratory of Phytochemistry and Plant Resources in West China (CUHK), The Chinese University of Hong KongHong Kong.
authors.forename: Clara Bik-San
authors.initials: CB
authors.lastname: Lau
keywords: Andrographis paniculata; Esophageal cancer; TM4SF3; anoikis; isoandrographolide; metastasis