Abstract
Prostate cancer is a major cause of cancer-related mortality in men in developed countries. The compound, 4-acetylantroquinonol B (4AAQB), is isolated from Antrodia cinnamomea (commonly known as Niu-Chang-Chih), which has been shown to inhibit cancer growth. However, the anticancer activity of 4AAQB has not previously been examined in prostate cancer. This study aimed to investigate the effect of 4AAQB on cancer and angiogenesis, as well as to explore its mechanism of action. Human prostate cancer cells (PC3) and human umbilical vein endothelial cells (HUVEC) were used in cell viability, cell migration, and cell cycle functional assays to evaluate the anticancer and antiangiogenic efficacy of 4AAQB in vitro. The effects of 4AAQB in vivo were determined using xenograft and angiogenesis models. The signaling events downstream of 4AAQB were also examined. The 4AAQB compound inhibited PC3 cell growth and migration, and reduced in vivo cancer growth, as shown in a subcutaneous xenograft model. Furthermore, 4AAQB inhibited HUVEC migration, tube formation, and aortic ring sprouting; it also reduced neovascularization in a Matrigel implant angiogenesis assay in vivo. The 4AAQB compound also decreased metastasis in the PC3 prostate cancer model in vivo. Serum or vascular endothelial growth factor (VEGF)-induced VEGF receptor 2 (VEGFR2), phosphoinositide 3-kinase (PI3K)/Ak strain transforming (Akt), and extracellular signal-regulated kinase ½ (ERK ½) phosphorylation were attenuated by 4AAQB in both PC3 and HUVEC. In conclusion, 4AAQB is a potential candidate for prostate cancer therapy.
Highlights
Prostate cancer is one of the most common malignancies worldwide and has a high mortality rate, with more than one million deaths a year
VEGF receptor 2 (VEGFR2) is the primary receptor for vascular endothelial growth factor (VEGF)-A stimulation and angiogenesis mediation, in part through the activation of the ERK1/2 and Ak strain transforming (Akt) signal transduction pathways [7]
Studies have shown that the inhibition of VEGF/phosphoinositide 3-kinase (PI3K)/mammalian targets of rapamycin/ERK signaling reduces angiogenesis, cancer growth, and metastasis [8,9]
Summary
Prostate cancer is one of the most common malignancies worldwide and has a high mortality rate, with more than one million deaths a year. It is frequently diagnosed in developed countries, especially in Europe and the United States, but the incidence of prostate cancer has increased in Asia, including Taiwan, over the past decade [1]. Novel and improved therapies, which can effectively control prostate cancer cell migration, invasion, and cancer-associated angiogenesis, are required to prevent cancer progression and increase the survival of patients diagnosed with prostate cancer. Studies have shown that the inhibition of VEGF/PI3K/mammalian targets of rapamycin (mTOR)/ERK signaling reduces angiogenesis, cancer growth, and metastasis [8,9]
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