title: Combination of Quercetin and 2-Methoxyestradiol Enhances Inhibition of Human Prostate Cancer LNCaP and PC-3 Cells Xenograft Tumor Growth.
abstract: 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.
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Feiya
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Liming
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Reproductive Immunology and Pharmacology, National Research Institute for Family Planning, Beijing, P.R. China.
authors.forename: Huiping
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, the First hospital of China Medical University, Shenyang, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience, Beijing Key Laboratory of Neural Regeneration and Repair, Capital Medical University, Beijing, P.R. China.
authors.forename: Zhiqing
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Urology, Beijing Chaoyang Hospital, Capital Medical University, Beijing, P.R. China.
authors.forename: Nianzeng
authors.initials: N
authors.lastname: Xing
mesh_terms: D000077584:2-Methoxyestradiol; D000818:Animals; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology*; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D047309:Flavones; D064593:Heterografts; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
chemical_list: D002867:Chromones; D047309:Flavones; D004958:Estradiol; D000077584:2-Methoxyestradiol; C079163:quercetagetin