hypericum and Adenocarcinoma

This article reviews complementary and alternative therapies for advanced prostate cancer. This is not a comprehensive survey of nontraditional therapies for prostate cancer. Rather, this review focuses on alternative and complementary therapies with published studies to evaluate efficacy and safety. Three areas are addressed: alternative forms of hormonal therapy, management of side effects of hormonal therapy, and management of skeletal complications.

Topics: Acupuncture; Adenocarcinoma; Androgen Antagonists; Androgens; Anemia; Anticarcinogenic Agents; Antineoplastic Agents; Antineoplastic Agents, Hormonal; Breast Neoplasms; Clinical Trials, Phase II as Topic; Complementary Therapies; Depression; Diphosphonates; Drugs, Chinese Herbal; Erythropoietin; Female; Flushing; Humans; Hypericum; Male; Multicenter Studies as Topic; Neoplasms, Hormone-Dependent; Osteoporosis; Phytotherapy; Pilot Projects; Plant Extracts; Prospective Studies; Prostatic Hyperplasia; Prostatic Neoplasms; Randomized Controlled Trials as Topic; Serenoa

Colon cancer affects 1.23 million people worldwide and is the third most common malignant disease in men and the second in women. The only curative treatment is surgical resection, but a significant number of patients develop local recurrence or distant metastases. One of the alternative treatment methods for colon cancer is photodynamic therapy (PDT). In recent years, hypericin (HYP) derived from Hypericum perforatum has been suggested as a strong candidate photosensitizer for PDT. Our interest is focused on the biophysical changes in colon cancer cells in relation to HYP-mediated PDT.. In this study, HYP-mediated PDT at 0.04, 0.08 or 0.15 μM HYP concentrations was performed in HT-29 colon adenocarcinoma cells and the Electron Paramagnetic Resonance (EPR) spectra of the spin labeled cells were obtained. Plasma membranes are already heterogeneous structures; the presence of cancer cells increased the heterogeneity and also fluidity of the plasma membranes. Therefore, the obtained spectra were evaluated by EPRSIMC program, which provides the calculation of heterogeneous structures up to four spectral components with different fluidity characteristics. Generally, two motional patterns were obtained from calculations and the number of them increased at the highest concentration. As the order parameters of the most populated components compared, an increase was observed depending on the HYP concentration. However, because of the heterogeneous structure of membrane, the order parameters of the less populated components did not exhibit a regular distribution.. After HYP-mediated PDT, concentration dependent changes were observed in the domain parameters indicating an increase in the HYP accumulation.

Topics: Adenocarcinoma; Anthracenes; Cell Membrane; Colonic Neoplasms; Computer Simulation; Cyclic N-Oxides; Electron Spin Resonance Spectroscopy; HT29 Cells; Humans; Hydrophobic and Hydrophilic Interactions; Hypericum; Membrane Fluidity; Neoplasm Recurrence, Local; Perylene; Photochemotherapy; Photosensitizing Agents; Plant Extracts; Spin Labels

Continuous use of St. John's wort decreases the bioavailabilities of a variety of drugs. This interaction is attributed to the induction of cytochrome P450 3A4 and/or P-glycoprotein. In this study, we aimed to examine the chronic effects of St. John's wort and its constituents, hyperforin and hypericin, on the expression and function of P-glycoprotein in an intestinal cell line, LS 180. We also examined the acute inhibitory effect of St. John's wort on P-glycoprotein by using LLC-GA5-COL150 cells, which overexpress P-glycoprotein. St. John's wort and hyperforin but not hypericin increased the expression of P-glycoprotein in LS 180 cells. Removal of St. John's wort resulted in a restoration of P-glycoprotein level within 48 h. The content of hyperforin in St. John's wort extract was high enough to induce P-glycoprotein, suggesting that the induction of P-glycoprotein by St. John's wort can be almost attributable to hyperforin. The LS 180 cells chronically exposed to St. John's wort or hyperforin exhibited the increase in the function of P-glycoprotein assessed by the efflux of digoxin, and the activities correlated well with P-glycoprotein level. On the other hand, St. John's wort and its two constituents did not show any acute effect on P-glycoprotein-mediated transport of digoxin. St. John's wort induced P-glycoprotein in vitro that functions as a drug efflux pump. Hyperforin is considered to be a primary cause of the inductive effect of St. John's wort. Long-term administration of St. John's wort may cause clinically significant decrease in the plasma concentrations of P-glycoprotein substrates.

Topics: Adenocarcinoma; Animals; Anthracenes; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport; Bridged Bicyclo Compounds; Cell Line, Tumor; Colonic Neoplasms; Digoxin; Humans; Hypericum; LLC-PK1 Cells; Perylene; Phloroglucinol; Plant Extracts; Rifampin; Swine; Terpenes; Transfection

1. Chronic use of Saint John's wort (SJW) has been shown to lower the bioavailability for a variety of co-administered drugs including indinavir, cyclosporin, and digoxin. Decreases in intestinal absorption through induction of the multidrug resistance transporter, P-glycoprotein (P-gp), may explain decreased bioavailability. 2. The present study characterized the response of P-gp to chronic and acute exposure of SJW and hypericin (HYP, a presumed active moiety within SJW) in an in vitro system. Experiments were performed with 3 to 300 microg ml(-1) of methanol-extracted SJW and 0.03 to 3 microM HYP, representing low to high estimates of intestinal concentrations. 3. In induction experiments, LS-180 intestinal carcinoma cells were exposed for 3 days to SJW, HYP, vehicle or a positive control (ritonavir). P-gp was quantified using Western blot analysis. P-gp expression was strongly induced by SJW (400% increase at 300 microg ml(-1)) and by HYP (700% at 3 microM) in a dose-dependent fashion. Cells chronically treated with SJW had decreased accumulation of rhodamine 123, a P-gp substrate, that was reversed with acute verapamil, a P-gp inhibitor. Fluorescence microscopy of intact cells validated these findings. In Caco-2 cell monolayers, SJW and HYP caused moderate inhibition of P-gp-attributed transport at the maximum concentrations tested. 4. SJW and HYP significantly induced P-gp expression at low, clinically relevant concentrations. Similar effects occurring in vivo may explain the decreased bioavailability of P-gp substrate drugs when co-administered with SJW.

Topics: Adenocarcinoma; Anthracenes; Antidepressive Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Biological Transport, Active; Blotting, Western; Caco-2 Cells; Colonic Neoplasms; Dose-Response Relationship, Drug; Drug Interactions; Drug Resistance, Multiple; Humans; Hypericum; Image Processing, Computer-Assisted; Microscopy, Fluorescence; Perylene; Protein Kinase C; Rhodamine 123; Ritonavir; Time Factors; Tumor Cells, Cultured; Verapamil