Suppressive Effect and Molecular Mechanism of Houttuynia cordata Thunb. Extract against Prostate Carcinogenesis and Castration-Resistant Prostate Cancer

• Published in: Cancers Vol. 13; no. 14; p. 3403
• Main Authors: Subhawa, Subhawat, Naiki-Ito, Aya, Kato, Hiroyuki, Naiki, Taku, Komura, Masayuki, Nagano-Matsuo, Aya, Yeewa, Ranchana, Inaguma, Shingo, Chewonarin, Teera, Banjerdpongchai, Ratana, Takahashi, Satoru
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 07.07.2021; MDPI
• Subjects: Acetic acid; Acids; Adenocarcinoma; AKT protein; Androgen receptors; Androgens; anti-proliferation; Apoptosis; Carcinogenesis; Caspase; Castration; Cell activation; Cell cycle; Cell migration; Cell proliferation; Chemopreventive agents; Diet; Down-regulation; Ethyl acetate; Experiments; Flavonoids; functional food; Herbs; Houttuynia cordata; Houttuynia cordata Thunb; Kinases; MAP kinase; Medicinal plants; Mesenchyme; natural extracts; Phenotypes; Phytochemicals; Prostate cancer; Proteins; Rutin; Stat3 protein; Tumor cell lines; Xenografts; United States > US; Japan
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers13143403

Houttuynia cordata Thunb. (HCT) is a well-known Asian medicinal plant with biological activities used in the treatment of many diseases including cancer. This study investigated the effects of HCT extract and its ethyl acetate fraction (EA) on prostate carcinogenesis and castration-resistant prostate cancer (CRPC). HCT and EA induced apoptosis in androgen-sensitive prostate cancer cells (LNCaP) and CRPC cells (PCai1) through activation of caspases, down-regulation of androgen receptor, and inactivation of AKT/ERK/MAPK signaling. Rutin was found to be a major component in HCT (44.00 ± 5.61 mg/g) and EA (81.34 ± 5.21 mg/g) in a previous study. Rutin had similar effects to HCT/EA on LNCaP cells and was considered to be one of the active compounds. Moreover, HCT/EA inhibited cell migration and epithelial-mesenchymal transition phenotypes via STAT3/Snail/Twist pathways in LNCaP cells. The consumption of 1% HCT-mixed diet significantly decreased the incidence of adenocarcinoma in the lateral prostate lobe of the Transgenic rat for adenocarcinoma of prostate model. Similarly, tumor growth of PCai1 xenografts was significantly suppressed by 1% HCT treatment. HCT also induced caspase-dependent apoptosis via AKT inactivation in both in vivo models. Together, the results of in vitro and in vivo studies indicate that HCT has inhibitory effects against prostate carcinogenesis and CRPC. This plant therefore should receive more attention as a source for the future development of non-toxic chemopreventive agents against various cancers.