kava and Prostatic-Neoplasms

There are several other alternative medicines apart from vitamins and minerals that the clinician should be aware of because they have grown in popularity in other fields of medicine. In time, these therapies should impact the arena of urologic oncology. Traditional Chinese Medicine, which includes acupuncture, is an area that has received some attention. The theory behind it can be quite daunting because it is so different from the theory behind Western Medical Science. In addition, exactly how acupuncture can be applied to a patient and its potential use in prostate cancer need to be addressed. Other herbal therapies for the patient experiencing symptoms related to a localized cancer diagnosis also need to be evaluated. St John's Wort for depression and Kava for anxiety are two examples of herbal alternatives that some prostate patients are inquiring about. Finally, Ginkgo biloba has received a great deal of attention in the media for erectile dysfunction, but there is a dearth of evidence in this area and the information that already exists can be misleading until further studies are conducted. Also, it is imperative that additional studies be performed in all of the above subjects as they relate to prostate cancer, but a general survey on alternative medicine use in urologic diseases is needed first before an adequate review of the most popular therapies can be published.

Topics: Acupuncture Therapy; Anti-Anxiety Agents; Anxiety; Depression; Drugs, Chinese Herbal; Erectile Dysfunction; Ericales; Evidence-Based Medicine; Ginkgo biloba; Humans; Kava; Male; Medicine, Chinese Traditional; Philosophy, Medical; Phytotherapy; Plant Extracts; Plants, Medicinal; Prostatic Neoplasms

Kava (Piper methysticum Forster) extract and its major kavalactones have been shown to block chemically induced lung tumor initiation in mouse models. Here we evaluated the chemopreventive effect of a kavalactone-rich Kava fraction B (KFB), free of flavokavains, on carcinogenesis in a transgenic adenocarcinoma of mouse prostate (TRAMP) model and characterized the prostate gene expression signatures. Male C57BL/6 TRAMP mice were fed AIN93M diet with or without 0.4% KFB from 8 wk of age. Mice were euthanized at 16 or 28 wk. The growth of the dorsolateral prostate (DLP) lobes in KFB-treated TRAMP mice was inhibited by 66% and 58% at the respective endpoint. Anterior and ventral prostate lobes in KFB-treated TRAMP mice were suppressed by 40% and 49% at 28 wk, respectively. KFB consumption decreased cell proliferation biomarker Ki-67 and epithelial lesion severity in TRAMP DLP, without detectable apoptosis enhancement. Real time qRT-PCR detection of mRNA from DLP at 28 wk showed decreased expression of cell cycle regulatory genes congruent with Ki-67 suppression. Microarray profiling of DLP mRNA indicated that "oncogene-like" genes related to angiogenesis and cell proliferation were suppressed by KFB but tumor suppressor, immunity, muscle/neuro, and metabolism-related genes were upregulated by KFB in both TRAMP and WT DLP. TRAMP mice fed KFB diet developed lower incidence of neuroendocrine carcinomas (NECa) (2 out of 14 mice) than those fed the basal diet (8 out of 14 mice, χ

Topics: Adenocarcinoma; Animals; Antineoplastic Agents, Phytogenic; Carcinogenesis; Female; Gene Expression Regulation, Neoplastic; Kava; Lactones; Male; Mice; Mice, Inbred C57BL; Prostate; Prostatic Neoplasms; Transcriptome; Transgenes

Men living in Fiji and drinking kava have low incidence of prostate cancer (PCa). However, the PCa incidence among Fijian men who had migrated to Australia, increased by 5.1-fold. We therefore examined the potential effects of kava root extracts and its active components (kavalactones and flavokawains) on PCa growth and androgen receptor (AR) expression. PCa cell lines (LNCaP, LAPC-4, 22Rv1, C4-2B, DU145 and PC-3) with different AR expression, and a transformed prostate myofibroblast cell line (WPMY-1), were treated with a commercial kava extract, kavalactones (kawain, 5'6'-dehydrokawain, yangonin, methysticin) and flavokawain B. Expression of AR and its target genes (PSA and TMPRSS2) was examined. Two novel patient-derived PCa xenograft models from high grade PCa specimens were established by implanting the specimens into nude mice and passing tumor pieces through subcutaneous injection in nude mice, and then treated with kava extract and flavokawain B to examine their effects on tumor growth, AR expression and serum PSA levels. The kava extract and flavokawain B effectively down-regulated the expression of both the full-length AR and AR splice variants. The kava extract and kavalactones accelerated AR protein degradation, while flavokawain B inhibited AR mRNA transcription via decreasing Sp1 expression and the binding of Sp1 to the AR promoter. The kava root extract and flavokawain B reduce tumor growth, AR expression in tumor tissues and levels of serum PSA in the patient-derived PCa xenograft models. These results suggest a potential usefulness of a safe kava product or its active components for prevention and treatment of advanced PCa by targeting AR.

Topics: Animals; Cell Proliferation; Down-Regulation; Humans; Kava; Male; Mice; Neoplasm Transplantation; Plants, Medicinal; Prostatic Neoplasms; Protein Isoforms; Receptors, Androgen; Transplantation, Heterologous; Tumor Burden