title: The dietary isoflavone biochanin-A sensitizes prostate cancer cells to TRAIL-induced apoptosis.
abstract: Biochanin-A, a major dietary isoflavone in soy and red clover, possesses anticancer and chemopreventive properties. Induction of apoptosis by naturally occurring dietary agents is an important event for cancer chemoprevention. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis selectively in cancer cells but not in normal cells. Soluble or expressed in immune cells, molecules TRAIL plays a significant role in surveillance and defense mechanisms against tumours. Prostate cancer is an ideal disease for nutritional prevention. The TRAIL-mediated apoptosis pathway in prostate cancer cells is an attractive target for chemopreventive activities of dietary agents. LNCaP and DU145 prostate cancer cells are resistant to TRAIL-induced apoptosis. We showed that biochanin-A markedly augmented TRAIL-induced cytotoxicity and apoptosis in both prostate cancer cell lines. Then, we investigated the mechanisms by which biochanin-A enhanced TRAIL-mediated apoptosis using the LNCaP cell line. The isoflavone sensitized the TRAIL-resistant LNCaP cells through the inhibition of transcription factor NF-κB(p65) activity, increased the expression of the death receptor TRAIL-R2 (DR5), and disrupted mitochondrial membrane potential (ΔΨm). Our study confirmed that biochanin-A overcame TRAIL-resistance by engaging both intrinsic and extrinsic apoptotic pathways and by regulating the NF-κB activity. The results suggested a potential role of biochanin-A in prostate cancer chemoprevention through the enhancement of TRAIL-mediated apoptosis.
authors.affiliation: Department of Microbiology and Immunology, Zabrze, Medical University of Silesia in Katowice, Katowice, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Szliszka
authors.forename: Zenon P
authors.initials: ZP
authors.lastname: Czuba
authors.forename: Anna
authors.initials: A
authors.lastname: Mertas
authors.forename: Andrzej
authors.initials: A
authors.lastname: Paradysz
authors.forename: Wojciech
authors.initials: W
authors.lastname: Krol
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D019833:Genistein / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008856:Microscopy, Fluorescence; D015394:Molecular Structure; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D007529:Isoflavones; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; D051996:Transcription Factor RelA; D019833:Genistein; C004541:biochanin A