Shih-Han Huang1, Yung-Hsi Kao2, Christo J F Muller3, Elizabeth Joubert4, Chih-Pin Chuu5. 1. Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; Department of Life Science, National Central University, Taoyuan City 32001, Taiwan. 2. Department of Life Science, National Central University, Taoyuan City 32001, Taiwan. 3. Biomedical Research and Innovation Platform (BRIP), South African Medical Research Council, Tygerberg 7505, South Africa; Division of Medical Physiology, Faculty of Health Sciences, Stellenbosch University, Tygerberg 7505, South Africa; Department of Biochemistry and Microbiology, University of Zululand, KwaDlangezwa 3886, South Africa. 4. Plant Bioactives Group, Post-Harvest and Agro-Processing Technologies, Agricultural Research Council (ARC), Infruitec-Nietvoorbij, Stellenbosch 7599, South Africa; Department of Food Science, Stellenbosch University, Stellenbosch 7599, South Africa. 5. Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli County 35053, Taiwan; PhD Program for Aging and Graduate Institute of Basic Medical Science, China Medical University, Taichung City 40402, Taiwan; Biotechnology Center, National Chung Hsing University, Taichung City 40227, Taiwan. Electronic address: cpchuu@gmail.com.
Abstract
BACKGROUND: More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-year survival rate of 25%. Previously, we reported that GRT, a standardized, pharmaceutical-grade aspalathin-rich extract (12.78 g aspalathin/100 g extract), prepared from green rooibos produced from the leaves and fine stems of Aspalathus linearis, inhibits the proliferation of PCa cells, meriting this investigation to determine if GRT can suppress the migration and invasion of castration-resistant prostate cancer (CRPC) cells. PURPOSE: In the present study, we investigated whether GRT extract can interfere with the migration and invasion of human CRPC cells. METHODS: Transwell assays were used to explore the effects of GRT on the migration and invasion of CRPC cells. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism(s). RESULTS: Treatment with 25-100 μg/ml GRT suppressed the migration and invasion of LNCaP C4-2B and 22Rv1 CRPC cells. MWA and Western blot analysis indicated that GRT treatment suppressed the protein level of yes-associated protein (YAP), macrophage stimulating 1 protein (MST1), phospho-MST1/phospho-MST2 T183/T180, and paxillin, but increased the abundance of E-cadherin. Over-expression of YAP rescued the suppressive effects of GRT on migration and invasion of CRPC cells. Treatment with the major flavonoid of GRT - the C-glucosyl dihydrochalcone, aspalathin - at a concentration of 75-100 μg/ml also reduced the migration and invasion of CRPC cells, and the inhibition was partially rescued by YAP over-expression. CONCLUSIONS: GRT treatment suppresses the migration and invasion of CRPC cells via inhibition of YAP signaling and paxillin.
BACKGROUND: More than 80% of advanced prostate cancer (PCa) cases have bone metastasis, with a 5-year survival rate of 25%. Previously, we reported that GRT, a standardized, pharmaceutical-grade aspalathin-rich extract (12.78 g aspalathin/100 g extract), prepared from green rooibos produced from the leaves and fine stems of Aspalathus linearis, inhibits the proliferation of PCa cells, meriting this investigation to determine if GRT can suppress the migration and invasion of castration-resistant prostate cancer (CRPC) cells. PURPOSE: In the present study, we investigated whether GRT extract can interfere with the migration and invasion of human CRPC cells. METHODS: Transwell assays were used to explore the effects of GRT on the migration and invasion of CRPC cells. Micro-Western Array (MWA) and Western blot analysis were carried out to unravel the underlying molecular mechanism(s). RESULTS: Treatment with 25-100 μg/ml GRT suppressed the migration and invasion of LNCaP C4-2B and 22Rv1 CRPC cells. MWA and Western blot analysis indicated that GRT treatment suppressed the protein level of yes-associated protein (YAP), macrophage stimulating 1 protein (MST1), phospho-MST1/phospho-MST2 T183/T180, and paxillin, but increased the abundance of E-cadherin. Over-expression of YAP rescued the suppressive effects of GRT on migration and invasion of CRPC cells. Treatment with the major flavonoid of GRT - the C-glucosyl dihydrochalcone, aspalathin - at a concentration of 75-100 μg/ml also reduced the migration and invasion of CRPC cells, and the inhibition was partially rescued by YAP over-expression. CONCLUSIONS: GRT treatment suppresses the migration and invasion of CRPC cells via inhibition of YAP signaling and paxillin.
Authors: Sinenhlanhla X H Mthembu; Christo J F Muller; Phiwayinkosi V Dludla; Evelyn Madoroba; Abidemi P Kappo; Sithandiwe E Mazibuko-Mbeje Journal: Molecules Date: 2021-10-18 Impact factor: 4.411