Enhanced Chemoprevention of Prostate Cancer by Combining Arctigenin with Green Tea and Quercetin in Prostate-Specific Phosphatase and Tensin Homolog Knockout Mice

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2024-01, Vol.14 (1), p.105
• Main Authors: Hao, Qiongyu, Henning, Susanne M, Magyar, Clara E, Said, Jonathan, Zhong, Jin, Rettig, Matthew B, Vadgama, Jaydutt V, Wang, Piwen
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; Adenocarcinoma; AKT protein; Analysis; Androgen receptors; Androgens; Angiogenesis; Animals; arctigenin; Bioavailability; Cancer therapies; Care and treatment; Cell culture; Cell cycle; Cell growth; Chemoprevention; Clinical trials; Cytotoxicity; Furans; Green tea; Identification and classification; Lignans - pharmacology; Lignans - therapeutic use; Lymphatic system; Male; Metastasis; Methods; Mice; Mice, Knockout; Older people; Phosphatase; Phosphatases; Phosphatidylinositol 3-Kinases; Phytochemicals; Properties; Prostate - drug effects; Prostate cancer; Prostatic intraepithelial neoplasia; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - prevention & control; PTEN knockout mouse; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Quercetin; Quercetin - pharmacology; Quercetin - therapeutic use; Tea; Tensins; Tumorigenesis; Tumors
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom14010105

The low bioavailability of most phytochemicals limits their anticancer effects in humans. The present study was designed to test whether combining arctigenin (Arc), a lignan mainly from the seed of , with green tea (GT) and quercetin (Q) enhances the chemopreventive effect on prostate cancer. We performed in vitro proliferation studies on different cell lines. We observed a strong synergistic anti-proliferative effect of GT+Q+Arc in exposing androgen-sensitive human prostate cancer LNCaP cells. The pre-malignant WPE1-NA22 cell line was more sensitive to this combination. No cytotoxicity was observed in normal prostate epithelial PrEC cells. For an in vivo study, 3-week-old, prostate-specific PTEN (phosphatase and tensin homolog) knockout mice were treated with GT+Q, Arc, GT+Q+Arc, or the control daily until 16 weeks of age. In vivo imaging using prostate-specific membrane antigen (PSMA) probes demonstrated that the prostate tumorigenesis was significantly inhibited by 40% (GT+Q), 60% (Arc at 30 mg/kg bw), and 90% (GT+Q+Arc) compared to the control. A pathological examination showed that all control mice developed invasive prostate adenocarcinoma. In contrast, the primary lesion in the GT+Q and Arc alone groups was high-grade prostatic intraepithelial neoplasia (PIN), with low-grade PIN in the GT+Q+Arc group. The combined effect of GT+Q+Arc was associated with an increased inhibition of the androgen receptor, the PI3K/Akt pathway, Ki67 expression, and angiogenesis. This study demonstrates that combining Arc with GT and Q was highly effective in prostate cancer chemoprevention. These results warrant clinical trials to confirm the efficacy of this combination in humans.