The botanical component p -hydroxycinnamic acid suppresses the growth and bone metastatic activity of human prostate can
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ORIGINAL ARTICLE – CANCER RESEARCH
The botanical component p‑hydroxycinnamic acid suppresses the growth and bone metastatic activity of human prostate cancer PC‑3 cells in vitro Masayoshi Yamaguchi1 · Tomiyasu Murata2 · Joe W. Ramos1 Received: 14 August 2020 / Accepted: 21 September 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Bone metastatic prostate cancer is one of the most common malignancies in developed countries and the second leading cause of cancer-related death in men. There remains no effective treatment for metastatic prostate cancer. We investigate here the anticancer effects of botanical component p-hydroxycinnamic acid (HCA) on the PC-3 cells in vitro model of bone metastatic human prostate cancer. Culturing with HCA (10–1000 nM) suppressed colony formation and growth of PC-3 cells. Mechanistically, culturing with HCA decreased protein levels of Ras, PI3K, Akt, MAPK, NF-κB p65 and β-catenin related to processes of cell signaling and transcription, and it increased levels of p21, p53, retinoblastoma and regucalcin, which are suppressors in carcinogenesis. These alterations can lead to suppression of cell growth. Furthermore, culturing with HCA increased cell death and caspase-3 levels. The effects of HCA on the growth and death of PC-3 cells were blocked by culturing with CH223191, an antagonist of aryl hydrocarbon receptor (AHR), suggesting that HCA effects are partly involved in AHR signaling. Interestingly, HCA suppressed the stimulatory effects of Bay K 8644, an agonist of L-type calcium channel, on the growth of PC-3 cells. Coculturing of PC-3 cells and preosteoblastic MC-3T3 E1 cells increased osteoblastic mineralization. This increase was not attenuated by treatment of HCA that stimulated mineralization. Notably, osteoclastogenesis from preosteoclastic RAW264.7 cells was enhanced by coculturing with PC-3 cells, and this enhancement was suppressed by treatment with HCA (10–1000 nM). Thus, HCA has anticancer effects on bone metastatic human prostate cancer, potentially providing a novel therapeutic tool. Keywords p-hydroxycinnamic acid · Prostate cancer · PC-3 cells · Cell proliferation · Cell death · Bone metastasis · Aryl hydrocarbon receptor · Bay K 8644
Introduction Bone metastatic prostate cancer is one of the most common malignancies and the second leading cause of cancerrelated death in men. Bone metastasis represents a common complication of various types of human cancer, with an incidence reach of up to 70–95% in multiple myeloma, up to 65–90% in prostate cancer, and about 65–75% in breast * Masayoshi Yamaguchi [email protected] 1
Cancer Biology Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, 701 Ilalo Street, Hawaii, HI 96813, USA
Laboratory of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Yagotoyama 150, Tempaku, Nagoya 468‑8503, Japan
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cancer (D’Oronzo et al. 2019; Zhang 2019; Probert et al. 2019; Sousa and Clezardin 2018). Prostate cancer preferentially metastasizes to bone, leading t
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