Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo

Background Prostate cancer is an important public health problem. It is an excellent candidate disease for chemo-prevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. Pygeum africanum (Prunus africana or Rosaceae) is an African prune (plum) tree found in tropical Africa. An extract from the bark of Pygeum africanum has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). More recently in the USA, the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment. Methods The anti-cancer potential of Pygeum africanum has been tested both in vitro (PC-3 and LNCaP cells) and in␣vivo (TRAMP mouse model). Results In tissue culture, ethanolic extracts (30%) of Pygeum africanum inhibited the growth of PC-3 and LNCaP cells; induced apoptosis and altered cell kinetics; down regulated ERα and PKC-α protein, and demonstrated good binding ability to both mouse uterine estrogen receptors and LNCaP human androgen receptors. TRAMP mice fed Pygeum africanum showed a significant reduction (P = 0.034) in prostate cancer incidence (35%) compared to casein fed mice (62.5%). Conclusion Pygeum africanum, which is widely used in Europe and USA for treatment of BPH, has a significant role in regulation of prostate cancer both in␣vitro and in␣vivo and therefore may be a useful supplement for people at high risk for developing prostate cancer

A human relevent rat model of breast cancer

Abstract only availableBecause women experience a bewildering array of chemicals, foods and lifestyles, only profound effects on preventing or promoting breast cancer are detectible in human studies. Subtle or delayed effects can be detected in animal models. Mammary tumors in ACI rats share important similarities with the majority of human breast cancers. The link between life time estrogen exposure and breast cancer risk in humans is well established. A high percentage of human breast cancers express ER, are stimulated to grow by the addition of exogenous estrogen, and respond to the antiestrogen tamoxifen. The ACI rat is the only rodent model in which estrogen-sensitive tumors are induced by estrogen. The ACI.COP-Ept2 substrain, derived from the ACI rat, develops mammary tumors similar to those of the ACI rat, but with reduced pituitary hyperplasia. We show that estrogen-induced mammary tumors in ACI.COP-Ept2 express ERα and respond to tamoxifen. Furthermore, tumors express ERβ, progesterone receptor and Her2/neu. The average latency was 183±6 days (n=24) and average tumor burden 1,107±415 mm3. The similarities of ACI.COP-Ept2 tumors to human breast cancers make this a valuable model for determining which of the myriad of lifestyle and diet choices reportedly protecting women from breast cancer actually reduce cancer incidence.Food for the 21st Century Undergraduate Research Program in Nutritional Science

Creation and preliminary characterization of a Tp53 knockout rat

SUMMARY The tumor suppressor TP53 plays a crucial role in cancer biology, and the TP53 gene is the most mutated gene in human cancer. Trp53 knockout mouse models have been widely used in cancer etiology studies and in search for a cure of cancer with some limitations that other model organisms might help overcome. Via pronuclear microinjection of zinc finger nucleases (ZFNs), we created a Tp53 knockout rat that contains an 11-bp deletion in exon 3, resulting in a frameshift and premature terminations in the open reading frame. In cohorts of 25 homozygous (Tp53Δ11/Δ11), 37 heterozygous (Tp53Δ11/+) and 30 wild-type rats, the Tp53Δ11/Δ11 rats lived an average of 126 days before death or removal from study because of clinical signs of abnormality or formation of tumors. Half of Tp53Δ11/+ were removed from study by 1 year of age because of tumor formation. Both Tp53Δ11/+ and Tp53Δ11/Δ11 rats developed a wide spectrum of tumors, most commonly sarcomas. Interestingly, there was a strikingly high incidence of brain lesions, especially in Tp53Δ11/Δ11 animals. We believe that this mutant rat line will be useful in studying cancer types rarely observed in mice and in carcinogenicity assays for drug development

Differential expression of FGF family members in a progestin-dependent BT-474 human breast cancer xenograft model

Members of the fibroblast growth factor (FGF) family have been associated with tumor progression and angiogenesis, though the mechanism through which they affect the progression of breast cancer remains elusive. We recently showed that progestins increase the production of the potent angiogenic factor VEGF in an in vivo BT-474 human breast cancer cell-derived xenograft model. In this study we sought to determine the effect of progesterone (P) on regulation of specific FGF family members (FGF-2, FGF-4 and FGF-8) in the same model. Using immunohistochemistry we found that treatment with P significantly reduced FGF-2 and FGF-8 levels, while modestly increasing the levels of FGF-4 in tumors collected at the termination of the study or soon after P treatment began. The in vivo observations with FGF-2 were confirmed in cultured BT-474 cells, though the P-mediated reduction in FGF-2 was not blocked by the anti-progestin RU-486, suggesting that classical progesterone receptors (PR) are not involved in FGF-2 down-regulation. Also, P did not affect levels of FGF-2 mRNA in BT-474 cells, indicating that P exerts its effects on FGF-2 post-transcriptionally. Our observations suggest that the in vivo stimulation of BT-474 cell growth by P is associated with down-regulation of FGF-2 and FGF-8. Furthermore, since FGF-4 levels increased during P-treatment, FGF-4 may be required for tumor growth and maintenance and might therefore be a potential therapeutic target through which to suppress P-dependent tumor growth

ICLAS LAQ Network for the Promotion of Animal Quality in Research

ICLAS Laboratory Animal Quality Network (LAQN) programs currently consist of the Performance Evaluation Program (PEP), which focuses on microbial monitoring by and for laboratory animal diagnostic laboratories, and the Genetic Reference Monitoring Program (GENRef), which provides assay-ready reference DNA for genetic testing of mouse strains. Since 2008, PEP has grown to become a truly international program with participating laboratories in 5 continents. Launched in 2016, GENRef currently distributes DNA from 12 common inbred mouse strains for use in genetic monitoring of locally inbred colonies as well as for genetic testing of stocks, particularly genetically engineered stocks, of uncertain origins. GENRef has the capacity to include additional strains as well as additional species. PEP and GENRef provide the reagents at cost, as a resource to the international scientific community, in the interest of improving research quality in an environment of growing concern for research quality, rigor, and reproducibility

Phytosterol Pygeum africanum regulates prostate cancer in vitro and in vivo

Background Prostate cancer is an important public health problem. It is an excellent candidate disease for chemo-prevention because prostate cancer is typically slow growing and is usually diagnosed in elderly males. Pygeum africanum (Prunus africana or Rosaceae) is an African prune (plum) tree found in tropical Africa. An extract from the bark of Pygeum africanum has been used in Europe as a prevention and treatment of prostate disorders including benign prostatic hypertrophy (BPH). More recently in the USA, the phytotherapeutic preparations of Pygeum africanum and Saw palmetto have been marketed for prostate health including prostate cancer prevention and treatment. Methods The anti-cancer potential of Pygeum africanum has been tested both in vitro (PC-3 and LNCaP cells) and in␣vivo (TRAMP mouse model). Results In tissue culture, ethanolic extracts (30%) of Pygeum africanum inhibited the growth of PC-3 and LNCaP cells; induced apoptosis and altered cell kinetics; down regulated ERα and PKC-α protein, and demonstrated good binding ability to both mouse uterine estrogen receptors and LNCaP human androgen receptors. TRAMP mice fed Pygeum africanum showed a significant reduction (P = 0.034) in prostate cancer incidence (35%) compared to casein fed mice (62.5%). Conclusion Pygeum africanum, which is widely used in Europe and USA for treatment of BPH, has a significant role in regulation of prostate cancer both in␣vitro and in␣vivo and therefore may be a useful supplement for people at high risk for developing prostate cancer.This is a manuscript of an article from Endocrine 31 (2007): 72. doi: 10.1007/s12020-007-0014-y. Posted with permission. "The original publication is available at www.springerlink.com".</p