Feiya Yang

Quercetin in prostate cancer: Chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential (Review)

The morbidity and mortality of prostate cancer have been increasing recently, and the comprehensive treatment for prostate cancer is unable to achieve satisfactory outcomes. Quercetin is a natural flavonoid compound that has attracted increased interest and attention due to its anticancer activity. In vitro and in vivo studies have verified that quercetin effectively inhibits prostate cancer via various mechanisms. Clinical trails concerning the pharmacokinetics and application of quercetin in humans have also obtained promising results. Meanwhile, epidemiologic studies have demonstrated a negative association between quercetin intake and prostate cancer incidence and have suggested a chemopreventive effect of quercetin on prostate cancer that has been exhibited in animal experiments. The main issue concerning quercetin utilization is its low bioavailability. Therefore, solutions to the issues concerning its use such as alteration of the molecular structure and combination therapy are in the exploratory stage. In the present review, the most important aspects of chemotherapeutic and chemopreventive effects, mechanisms and clinical application potential of quercetin in prostate cancer are summarized.

Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth.

Quercetin and 2-Methoxyestradiol (2-ME) are promising anti-cancer substances. Our previous in vitro study showed that quercetin synergized with 2-Methoxyestradiol exhibiting increased antiproliferative and proapoptotic activity in both androgen-dependent LNCaP and androgen-independent PC-3 human prostate cancer cell lines. In the present study, we determined whether their combination could inhibit LNCaP and PC-3 xenograft tumor growth in vivo and explored the underlying mechanism. Human prostate cancer LNCaP and PC-3 cells were inoculated subcutaneously in male BALB/c nude mice. When xenograft tumors reached about 100 mm3, mice were randomly allocated to vehicle control, quercetin or 2-Methoxyestradiol singly treated and combination treatment groups. After therapeutic intervention for 4 weeks, combination treatment of quercetin and 2-ME i) significantly inhibited prostate cancer xenograft tumor growth by 46.8% for LNCaP and 51.3% for PC-3 as compared to vehicle control group, more effective than quercetin (28.4% for LNCaP, 24.8% for PC3) or 2-ME (32.1% for LNCaP, 28.9% for PC3) alone; ii) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; iii) led to higher Bax/Bcl-2 ratio, cleaved caspase-3 protein expression and apoptosis rate; and iv) resulted in lower phosphorylated AKT (pAKT) protein level, vascular endothelial growth factor protein and mRNA expression, microvascular density and proliferation rate than single drug treatment. These effects were more remarkable compared to vehicle group. Therefore, combination of quercetin and 2-ME can serve as a novel clinical treatment regimen owning the potential of enhancing antitumor effect on prostate cancer in vivo and lessening the dose and side effects of either quercetin or 2-ME alone. These in vivo results will lay a further solid basis for subsequent researches on this novel therapeutic regimen in human prostate cancer.

Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo

The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interests of researchers to find novel cancer therapies aiming to inhibit angiogenesis and tumor growth. Quercetin is a flavonoid compound that widely exists in the nature. Our previous study preliminarily demonstrated that quercetin effectively inhibited human prostate cancer cell xenograft tumor growth by inhibiting angiogenesis. Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose-dependent manner; ⅱ) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); ⅲ) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; ⅳ) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.

Quercetin protects against chronic prostatitis in rat model through NF-κB and MAPK signaling pathways

Chronic Prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a common disease of urology, of which the pathogenesis and therapy remain to be further elucidated. Quercetin has been reported to improve the symptoms of CP/CPPS patients. We aimed to verify the therapeutic effect of quercetin on CP/CPPS and identify the mechanism responsible for it.

Self-retaining barbed suture reduces warm ischemia time during laparoscopic partial nephrectomy

Abstract Objective: To evaluate the efficacy and safety of self-retaining barbed suture in renorrhaphy during laparoscopic partial nephrectomy by comparing surgical outcomes in a prospective randomized manner. Material and methods: From July 2014 to July 2015, a total of 60 patients with T1 renal tumor were randomized into two equal groups: self-retaining barbed suture (SRBS) and conventional absorbable polyglactin suture (non-SRBS group). All patients were treated by retroperitoneal laparoscopic partial nephrectomy. One surgeon with high volume experience performed all procedures. The patient demographics and perioperative outcomes were compared. Results: The patient demographics and tumor characteristics were comparable. The mean tumor size and R.E.N.A.L. scores were comparable between the two groups. LPN was successfully accomplished in all patients without open conversion. The warm ischemia and renorrhaphy times were significantly shorter in the SRBS group (18.8 ± 8.2 vs. 22.9 ± 7.3 min, P = .04; 10.4 ± 3.7 vs. 13.8 ± 5.6 min, P = .01). The minor complication rate was 13.3% vs. 10.0%, which was comparable. No major complication occurred. Conclusions: The randomized controlled trial demonstrates that SRBS for renorrhaphy during retroperitoneal laparoscopic partial nephrectomy is safe and efficient. Application of barbed suture simplifies the parenchymal repair procedure and reduces warm ischemia time in comparison with conventional suture.

A Retrospective Study Comparing Surgical and Early Oncological Outcomes between Intracorporeal and Extracorporeal Ileal Conduit after Laparoscopic Radical Cystectomy from a Single Center

Background: Robot-assisted/laparoscopic intracorporeal ileal conduit (ICIC) has been reported in many experienced centers. Whether laparoscopic ICIC is superior to extracorporeal ileal conduit (ECIC) and whether laparoscopic ICIC should be promoted is still controversial. The aim of the study was to compare surgical and early oncological outcomes between patients undergoing laparoscopic radical cystectomy (LRC) with ICIC and ECIC. Methods: From January 2011 to June 2016, a total of 45 patients with bladder cancer underwent LRC with ileal conduit at our department, of whom 20 patients underwent LRC with ECIC and 25 patients underwent LRC with ICIC. Data of each patients characteristics, surgical outcomes, and short-term oncological outcomes were collected and analyzed. Results: LRC with ileal conduit was performed successfully on all 45 patients. There were no significant differences in patients’ characteristics, mean total operative time, and mean estimated blood loss between the ICIC and ECIC groups. Median time of flatus and oral intake was shorter in the ICIC group compared with the ECIC group (3 vs. 5 days, P = 0.035; 4 vs. 5 days, P = 0.002). The complications rates did not show significant difference between the two groups within the first 90 days postoperatively (P = 0.538). Cancer staging showed 45% of patients in the ECIC group and 36% in the ICIC group had a pathologic stage of T3 or T4, and 50% of patients in the ECIC group and 44% in the ICIC group had a pathologic stage of N1 or N1+. Kaplan–Meier analysis showed no significant difference in overall survival at 24 months (60% vs. 62%, P = 0.857) between the ECIC and ICIC groups. Conclusions: ICIC after LRC may be successful with the benefits of faster recovery time. No significant difference was found in complications and oncological outcomes between ICIC and ECIC. However, larger series with longer follow-up are needed to validate this procedure.

Galanin suppresses proliferation of human U251 and T98G glioma cells via its subtype 1 receptor

Abstract Galanin is a neuropeptide with a widespread distribution throughout the nervous and endocrine systems, and recent studies have shown an anti-proliferative effect of galanin on several types of tumors. However, whether and how galanin and its receptors are involved in the regulation of cell proliferation in glioma cells remains unclear. In this study, the roles of galanin and its subtype 1 receptor (GAL1) in the proliferation of human U251 and T98G glioma cells were investigated. We found that galanin significantly suppressed the proliferation of U251 and T98G cells as well as tumor growth in nude mice. However, galanin did not exert apoptotic or cytotoxic effects on these two cell lines. In addition, we showed that galanin decreased the proliferation of U251 and T98G cells via its GAL1 receptor. Finally, we found that the GAL1 receptor was involved in the suppressive effects of galanin by activating ERK1/2.

AB170. Quercetin inhibits angiogenesis through thrombospondin-1 up-regulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo.

Objective To explore the important role of TSP-1 up-regulation in inhibiting angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. Methods Human prostate cancer androgen-independent PC-3 cells and Human umbilical vein endothelial cells (HUVECs) were cultured with vary dose of quercetin for certain time. PC-3 cells were inoculated subcutaneously in male BALB/c nude mouse. When xenograft tumors reached about 100 mm3, mouse were randomly allocated and treated. Tumor size and mouse weight were recorded. Relevant biomarkers of cells and tumor tissues were analyzed. Results After the varied doses were used for a certain time, quercetin (I) significantly inhibited PC-3 and (HUVECs) proliferation, migration and invasion in a dose dependent way; (II) effectively inhibited prostate cancer PC-3 cells xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); (III) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; (IV) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose dependent way. Conclusions Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.