Quercetin and Its Nano-Scale Delivery Systems in Prostate Cancer Therapy: Paving the Way for Cancer Elimination and Reversing Chemoresistance

Simple Summary Epidemiological studies have shown a negative correlation between the consumption of quercetin and the incidence of prostate cancer, and have indicated a chemo preventive effect of quercetin on prostate cancer in animal models. The major issues associated with quercetin are its low bioavailability and rapid metabolism, and priority attention needs to be addressed to cope with these. Chemoresistance is another of the main negative features concerning prostate cancer treatments. The current review highlights the chemotherapeutic effect, chemo preventive effect, and chemoresistance elimination potential of quercetin in prostate cancer. Quercetin nano scale delivery has been proven to overcome the issues mentioned, however, further studies are required on its nanoscale delivery to make it a next generation agent for the complete eradication of prostate cancer. Abstract Prostate cancer is the second most leading and prevalent malignancy around the world, following lung cancer. Prostate cancer is characterized by the uncontrolled growth of cells in the prostate gland. Prostate cancer morbidity and mortality have grown drastically, and intensive prostate cancer care is unlikely to produce adequate outcomes. The synthetic drugs for the treatment of prostate cancer in clinical practice face several challenges. Quercetin is a natural flavonoid found in fruits and vegetables. Apart from its beneficial effects, its plays a key role as an anti-cancer agent. Quercetin has shown anticancer potential, both alone and in combination. Therefore, the current study was designed to collect information from the literature regarding its therapeutic significance in the treatment of prostate cancer. Studies performed both in vitro and in vivo have confirmed that quercetin effectively prevents prostate cancer through different underlying mechanisms. Promising findings have also been achieved in clinical trials regarding the pharmacokinetics and human applications of quercetin. In the meantime, epidemiological studies have shown a negative correlation between the consumption of quercetin and the incidence of prostate cancer, and have indicated a chemopreventive effect of quercetin on prostate cancer in animal models. The major issues associated with quercetin are its low bioavailability and rapid metabolism, and these require priority attention. Chemoresistance is another main negative feature concerning prostate cancer treatment. This review highlights the chemotherapeutic effect, chemo preventive effect, and chemoresistance elimination potential of quercetin in prostate cancer. The underlying mechanisms for elimination of prostate cancer and eradication of resistance, either alone or in combination with other agents, are also discussed. In addition, the nanoscale delivery of quercetin is underpinned along with possible directions for future study.

[1]  Yu-Ling Zhang,et al.  Association of Caveolin-1 Expression With Prostate Cancer: A Systematic Review and Meta-Analysis , 2021, Frontiers in Oncology.

[2]  S. Ouyang,et al.  Marine-derived drugs: Recent advances in cancer therapy and immune signaling. , 2020, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[3]  Prabhanjan S. Giram,et al.  LHRH-conjugated, PEGylated, poly-lactide-co-glycolide nanocapsules for targeted delivery of combinational chemotherapeutic drugs Docetaxel and Quercetin for prostate cancer. , 2020, Materials science & engineering. C, Materials for biological applications.

[4]  N. Xing,et al.  Quercetin Inhibits Epithelial-to-Mesenchymal Transition (EMT) Process and Promotes Apoptosis in Prostate Cancer via Downregulating lncRNA MALAT1 , 2020, Cancer management and research.

[5]  N. Xing,et al.  Quercetin reverses docetaxel resistance in prostate cancer via androgen receptor and PI3K/Akt signaling pathways , 2020, International journal of biological sciences.

[6]  Xue-Ting Deng,et al.  Pharmacological basis and new insights of quercetin action in respect to its anti-cancer effects. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[7]  K. Takayama,et al.  Ginsenoside Rb1 inhibits vascular calcification as a selective androgen receptor modulator. , 2019, European journal of pharmacology.

[8]  T. Efferth,et al.  MicroRNA targeting by quercetin in cancer treatment and chemoprotection. , 2019, Pharmacological research.

[9]  Xiang-chun Shen,et al.  A Novel Tanshinone Analog Exerts Anti-Cancer Effects in Prostate Cancer by Inducing Cell Apoptosis, Arresting Cell Cycle at G2 Phase and Blocking Metastatic Ability , 2019, International journal of molecular sciences.

[10]  Z. Khazaei,et al.  Global cancer statistics 2018: Globocan estimates of incidence and mortality worldwide prostate cancers and their relationship with the human development index , 2019, Advances in Human Biology.

[11]  T. Karpiński,et al.  Fucoxanthin—An Antibacterial Carotenoid , 2019, Antioxidants.

[12]  K. Clark,et al.  RNase L Induces Expression of A Novel Serine/Threonine Protein Kinase, DRAK1, to Promote Apoptosis , 2019, International journal of molecular sciences.

[13]  B. Salehi,et al.  Phytochemicals in Prostate Cancer: From Bioactive Molecules to Upcoming Therapeutic Agents , 2019, Nutrients.

[14]  M. Hsiao,et al.  Targeting the SPOCK1-snail/slug axis-mediated epithelial-to-mesenchymal transition by apigenin contributes to repression of prostate cancer metastasis , 2019, Journal of experimental & clinical cancer research : CR.

[15]  A. Bishayee,et al.  Targeting autophagy using natural compounds for cancer prevention and therapy , 2019, Cancer.

[16]  M. Shariati,et al.  Luteolin, a flavonoid, as an anticancer agent: A review. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[17]  Mhd Anas Tomeh,et al.  A Review of Curcumin and Its Derivatives as Anticancer Agents , 2019, International journal of molecular sciences.

[18]  C. Putterman,et al.  Constitutive reduction in the checkpoint inhibitor, CTLA-4, does not accelerate SLE in NZM 2328 mice , 2019, Lupus Science & Medicine.

[19]  R. Agarwal,et al.  Exosome proteomic analyses identify inflammatory phenotype and novel biomarkers in African American prostate cancer patients , 2019, Cancer medicine.

[20]  R. Weinberg,et al.  New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer , 2018, Nature reviews. Molecular cell biology.

[21]  H. Rammensee,et al.  Impact of curative radiotherapy on the immune status of patients with localized prostate cancer , 2018, Oncoimmunology.

[22]  P. Ascierto,et al.  CheckMate-032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer , 2018, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[23]  F. Yazdian,et al.  Development and characterization of a novel cationic PEGylated niosome-encapsulated forms of doxorubicin, quercetin and siRNA for the treatment of cancer by using combination therapy , 2018, Artificial cells, nanomedicine, and biotechnology.

[24]  Ping Liu,et al.  Metformin combined with quercetin synergistically repressed prostate cancer cells via inhibition of VEGF/PI3K/Akt signaling pathway. , 2018, Gene.

[25]  S. Ramakrishna,et al.  Recent advances in core/shell bicomponent fibers and nanofibers: A review , 2018 .

[26]  D. Trump,et al.  Vitamin D in prostate cancer , 2018, Asian journal of andrology.

[27]  R. Chen,et al.  Anticancer Activity of Anthopleura anjunae Oligopeptides in Prostate Cancer DU-145 Cells , 2018, Marine drugs.

[28]  C. Bokemeyer,et al.  Synthesis and anticancer activity of the derivatives of marine compound rhizochalin in castration resistant prostate cancer , 2018, Oncotarget.

[29]  P. Kantoff,et al.  Current treatment strategies for advanced prostate cancer , 2018, International journal of urology : official journal of the Japanese Urological Association.

[30]  R. Tiwari,et al.  Medicinal and Therapeutic Potential of Herbs and Plant Metabolites / Extracts Countering Viral Pathogens - Current Knowledge and Future Prospects. , 2018, Current drug metabolism.

[31]  S. Kawato,et al.  Modulation of AKR1C2 by curcumin decreases testosterone production in prostate cancer , 2018, Cancer science.

[32]  B. Aggarwal,et al.  Chronic diseases, inflammation, and spices: how are they linked? , 2018, Journal of Translational Medicine.

[33]  Zhen Liang,et al.  Quercetin reverses the doxorubicin resistance of prostate cancer cells by downregulating the expression of c-met , 2017, Oncology letters.

[34]  A. D. Meglio,et al.  Targeting androgen-independent pathways: new chances for patients with prostate cancer? , 2017, Critical reviews in oncology/hematology.

[35]  T. Yasui,et al.  Association of a common genetic variant in RNASEL and prostate cancer susceptibility , 2017, Oncotarget.

[36]  A. Aynacioglu,et al.  Dual inhibition of P-glycoprotein and midkine may increase therapeutic effects of anticancer drugs. , 2017, Medical hypotheses.

[37]  N. Sharifi,et al.  Androgen Signaling in Prostate Cancer. , 2017, Cold Spring Harbor perspectives in medicine.

[38]  I. Melero,et al.  Anti-CD137 and PD-1/PD-L1 Antibodies En Route toward Clinical Synergy , 2017, Clinical Cancer Research.

[39]  A. Nalla.  NOVEL HERBAL DRUG DELIVERY SYSTEM - AN OVERVIEW , 2017 .

[40]  Junjiang Fu,et al.  Resveratrol enhances polyubiquitination-mediated ARV7 degradation in prostate cancer cells , 2017, Oncotarget.

[41]  Matthew R. Cooperberg,et al.  Epidemiology of prostate cancer , 2017, World Journal of Urology.

[42]  P. Wee,et al.  Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways , 2017, Cancers.

[43]  Leaf Huang,et al.  Quercetin Remodels the Tumor Microenvironment To Improve the Permeation, Retention, and Antitumor Effects of Nanoparticles. , 2017, ACS nano.

[44]  H. Bahmad,et al.  Prostate Cancer and Aspirin Use: Synopsis of the Proposed Molecular Mechanisms , 2017, Front. Pharmacol..

[45]  Aamir Ahmad,et al.  Cancer Chemoprevention by Phytochemicals: Nature’s Healing Touch , 2017, Molecules.

[46]  J. Li,et al.  Celastrol, an active constituent of the TCM plant Tripterygium wilfordii Hook.f., inhibits prostate cancer bone metastasis , 2017, Prostate Cancer and Prostatic Diseases.

[47]  Zhiquan Hu,et al.  Curcumin induces apoptosis and protective autophagy in castration-resistant prostate cancer cells through iron chelation , 2017, Drug design, development and therapy.

[48]  A. Houtsmuller,et al.  Structure of the homodimeric androgen receptor ligand-binding domain , 2017, Nature Communications.

[49]  M. I. Gubarev,et al.  Herbal Medicines: challenges in the modern world. Part 5. status and current directions of complementary and alternative herbal medicine worldwide , 2016, Expert review of clinical pharmacology.

[50]  Ajazuddin,et al.  Recent expansion of pharmaceutical nanotechnologies and targeting strategies in the field of phytopharmaceuticals for the delivery of herbal extracts and bioactives. , 2016, Journal of controlled release : official journal of the Controlled Release Society.

[51]  U. Lindequist.  Marine-Derived Pharmaceuticals – Challenges and Opportunities , 2016, Biomolecules & therapeutics.

[52]  B. Lokeshwar,et al.  Bioactive natural products for chemoprevention and treatment of castration-resistant prostate cancer. , 2016, Seminars in cancer biology.

[53]  N. Sharma,et al.  Quercetin modulates Wnt signaling components in prostate cancer cell line by inhibiting cell viability, migration, and metastases , 2016, Tumor Biology.

[54]  K. Sak,et al.  Molecular mechanisms of action of quercetin in cancer: recent advances , 2016, Tumor Biology.

[55]  S. A. Ganai.  Histone deacetylase inhibitor sulforaphane: The phytochemical with vibrant activity against prostate cancer. , 2016, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[56]  Vani Mamillapalli.  Nanoparticles for Herbal Extracts , 2016 .

[57]  V. Adhami,et al.  Dietary flavonoid fisetin for cancer prevention and treatment. , 2016, Molecular nutrition & food research.

[58]  Amrish Kumar,et al.  Nasal-nanotechnology: revolution for efficient therapeutics delivery , 2016, Drug delivery.

[59]  Z. Mei,et al.  Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo. , 2016, Oncology reports.

[60]  J. Zhao,et al.  Quercetin-loaded nanomicelles to circumvent human castration-resistant prostate cancer in vitro and in vivo. , 2016, Nanoscale.

[61]  Soon-Cheol Ahn,et al.  Autophagy inhibition enhances silibinin-induced apoptosis by regulating reactive oxygen species production in human prostate cancer PC-3 cells. , 2015, Biochemical and biophysical research communications.

[62]  Yongfang Jiang,et al.  Suppression of HSP27 increases the anti-tumor effects of quercetin in human leukemia U937 cells , 2015, Molecular medicine reports.

[63]  G. D'andrea.  Quercetin: A flavonol with multifaceted therapeutic applications? , 2015, Fitoterapia.

[64]  Hai-yan Song,et al.  Effect of quercetin on the proliferation of the human ovarian cancer cell line SKOV-3 in vitro. , 2015, Experimental and therapeutic medicine.

[65]  S. Sandhu,et al.  Isothiocyanates: a class of bioactive metabolites with chemopreventive potential , 2015, Tumor Biology.

[66]  Zhengrong Huang,et al.  Berberine targets epidermal growth factor receptor signaling to suppress prostate cancer proliferation in vitro. , 2015, Molecular medicine reports.

[67]  J. Vadgama,et al.  Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells. , 2015, Molecular nutrition & food research.

[68]  Junhua Zheng,et al.  Combination of quercetin and hyperoside inhibits prostate cancer cell growth and metastasis via regulation of microRNA‑21. , 2015, Molecular medicine reports.

[69]  Yuehua Wu,et al.  Mitochondrial protein cyclophilin-D-mediated programmed necrosis attributes to berberine-induced cytotoxicity in cultured prostate cancer cells. , 2014, Biochemical and biophysical research communications.

[70]  M. Qureshi,et al.  Targeting cancer with nano-bullets: curcumin, EGCG, resveratrol and quercetin on flying carpets. , 2014, Asian Pacific journal of cancer prevention : APJCP.

[71]  Helmut Klocker,et al.  Oncogenic functions of IGF1R and INSR in prostate cancer include enhanced tumor growth, cell migration and angiogenesis , 2014, Oncotarget.

[72]  Jai-Sing Yang,et al.  The roles of endoplasmic reticulum stress and mitochondrial apoptotic signaling pathway in quercetin‐mediated cell death of human prostate cancer PC‐3 cells , 2014, Environmental toxicology.

[73]  J. Arbiser,et al.  Honokiol inhibits androgen receptor activity in prostate cancer cells , 2014, The Prostate.

[74]  S. Doty,et al.  Curcumin Inhibits Prostate Cancer Bone Metastasis by Up-Regulating Bone Morphogenic Protein-7 in Vivo. , 2014, Journal of cancer therapy.

[75]  S. Chiu,et al.  YB-1 expression promotes epithelial-to-mesenchymal transition in prostate cancer that is inhibited by a small molecule fisetin , 2014, Oncotarget.

[76]  Marlus Chorilli,et al.  Nanotechnology-based drug delivery systems and herbal medicines: a review , 2013, International journal of nanomedicine.

[77]  N. Xing,et al.  Quercetin synergizes with 2-methoxyestradiol inhibiting cell growth and inducing apoptosis in human prostate cancer cells. , 2013, Oncology reports.

[78]  Z. Ye,et al.  Curcumin induces cell cycle arrest and apoptosis of prostate cancer cells by regulating the expression of IkappaBalpha, c-Jun and androgen receptor. , 2013, Die Pharmazie.

[79]  Patricia D. Castro,et al.  Celastrol Suppresses Tumor Cell Growth through Targeting an AR-ERG-NF-κB Pathway in TMPRSS2/ERG Fusion Gene Expressing Prostate Cancer , 2013, PloS one.

[80]  S. Sandhu,et al.  Pharmacological and therapeutic potential of Cordyceps with special reference to Cordycepin , 2013, 3 Biotech.

[81]  Xianglin Shi,et al.  Quercetin Inhibits Angiogenesis Mediated Human Prostate Tumor Growth by Targeting VEGFR- 2 Regulated AKT/mTOR/P70S6K Signaling Pathways , 2012, PloS one.

[82]  R. Bruno,et al.  Acute, quercetin-induced reductions in blood pressure in hypertensive individuals are not secondary to lower plasma angiotensin-converting enzyme activity or endothelin-1: nitric oxide. , 2012, Nutrition research.

[83]  Vineet Kumar,et al.  Plant Extract Synthesized PLA Nanoparticles for Controlled and Sustained Release of Quercetin: A Green Approach , 2012, PloS one.

[84]  G. Di Lorenzo,et al.  Sipuleucel‐T (Provenge®) for castration‐resistant prostate cancer , 2012, BJU international.

[85]  W. V. van Cappellen,et al.  Stepwise androgen receptor dimerization , 2012, Journal of Cell Science.

[86]  Seoung Woo Shin,et al.  Autophagy inhibition enhances ursolic acid-induced apoptosis in PC3 cells. , 2012, Biochimica et biophysica acta.

[87]  Jihyeung Ju,et al.  Inhibition of IGF-1 Signaling by Genistein: Modulation of E-Cadherin Expression and Downregulation of β-Catenin Signaling in Hormone Refractory PC-3 Prostate Cancer Cells , 2012, Nutrition and cancer.

[88]  Oliver Sartor,et al.  Berberine Suppresses Androgen Receptor Signaling in Prostate Cancer , 2011, Molecular Cancer Therapeutics.

[89]  P. Elumalai,et al.  Quercetin inhibits invasion, migration and signalling molecules involved in cell survival and proliferation of prostate cancer cell line (PC‐3) , 2011, Cell biochemistry and function.

[90]  Masayuki Yamamoto,et al.  Molecular mechanisms of the Keap1–Nrf2 pathway in stress response and cancer evolution , 2011, Genes to cells : devoted to molecular & cellular mechanisms.

[91]  A. Baniahmad,et al.  The natural compounds atraric acid and N-butylbenzene-sulfonamide as antagonists of the human androgen receptor and inhibitors of prostate cancer cell growth , 2011, Molecular and Cellular Endocrinology.

[92]  M. Vijjeswarapu,et al.  Luteolin and gefitinib regulation of EGF signaling pathway and cell cycle pathway genes in PC-3 human prostate cancer cells , 2010, The Journal of Steroid Biochemistry and Molecular Biology.

[93]  F. Saad,et al.  Current management of castrate-resistant prostate cancer. , 2010, Current oncology.

[94]  L. Howard,et al.  Solubility and solution thermodynamic properties of quercetin and quercetin dihydrate in subcritical water , 2010 .

[95]  S. Shankar,et al.  The dietary bioflavonoid quercetin synergizes with epigallocathechin gallate (EGCG) to inhibit prostate cancer stem cell characteristics, invasion, migration and epithelial-mesenchymal transition , 2010, Journal of molecular signaling.

[96]  K. Selvakumar,et al.  Quercetin regulates insulin like growth factor signaling and induces intrinsic and extrinsic pathway mediated apoptosis in androgen independent prostate cancer cells (PC-3) , 2010, Molecular and Cellular Biochemistry.

[97]  K. To,et al.  Anticancer Effect and Structure-Activity Analysis of Marine Products Isolated from Metabolites of Mangrove Fungi in the South China Sea , 2010, Marine drugs.

[98]  C. Drake,et al.  Update: Immunological Strategies for Prostate Cancer , 2010, Current urology reports.

[99]  S. Hong,et al.  Lipid raft cholesterol and genistein inhibit the cell viability of prostate cancer cells via the partial contribution of EGFR-Akt/p70S6k pathway and down-regulation of androgen receptor. , 2010, Biochemical and biophysical research communications.

[100]  David W. Johnson,et al.  Silibinin--a promising new treatment for cancer. , 2010, Anti-cancer agents in medicinal chemistry.

[101]  Jeonghoon Heo,et al.  Quercetin enhances TRAIL-induced apoptosis in prostate cancer cells via increased protein stability of death receptor 5. , 2010, Life sciences.

[102]  S. Ylä-Herttuala,et al.  Nrf2-dependent and -independent Responses to Nitro-fatty Acids in Human Endothelial Cells , 2009, The Journal of Biological Chemistry.

[103]  S. Spivack,et al.  Dietary chemoprevention strategies for induction of phase II xenobiotic-metabolizing enzymes in lung carcinogenesis: A review. , 2009, Lung cancer.

[104]  M. Khanfar,et al.  Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products. , 2009, Bioorganic & medicinal chemistry.

[105]  J. Reynolds,et al.  The dietary bioflavonoid, quercetin, selectively induces apoptosis of prostate cancer cells by down‐regulating the expression of heat shock protein 90 , 2008, The Prostate.

[106]  H. Mukhtar,et al.  A novel dietary flavonoid fisetin inhibits androgen receptor signaling and tumor growth in athymic nude mice. , 2008, Cancer research.

[107]  D. Pookot,et al.  Genistein down-regulates androgen receptor by modulating HDAC6-Hsp90 chaperone function , 2008, Molecular Cancer Therapeutics.

[108]  N. Davies,et al.  Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo. , 2008, Carcinogenesis.

[109]  Xin-yang Wang,et al.  A novel anti-cancer effect of genistein: reversal of epithelial mesenchymal transition in prostate cancer cells , 2008, Acta Pharmacologica Sinica.

[110]  D. Lee,et al.  Quercetin augments TRAIL-induced apoptotic death: involvement of the ERK signal transduction pathway. , 2008, Biochemical pharmacology.

[111]  P. Vandenabeele,et al.  Treatment of PC‐3 and DU145 prostate cancer cells by prenylflavonoids from hop (Humulus lupulus L.) induces a caspase‐independent form of cell death , 2008, Phytotherapy research : PTR.

[112]  R. Silverman,et al.  Small self-RNA generated by RNase L amplifies antiviral innate immunity , 2007, Nature.

[113]  D. Hou,et al.  Action of Nrf2 and Keap1 in ARE-mediated NQO1 expression by quercetin. , 2007, Free radical biology & medicine.

[114]  Yong J. Lee,et al.  TRAIL apoptosis is enhanced by quercetin through Akt dephosphorylation , 2007, Journal of cellular biochemistry.

[115]  D. Nebert,et al.  The role of cytochrome P450 enzymes in endogenous signalling pathways and environmental carcinogenesis , 2006, Nature Reviews Cancer.

[116]  S. Yeh,et al.  Effects of quercetin on beta-apo-8'-carotenal-induced DNA damage and cytochrome P1A2 expression in A549 cells. , 2006, Chemico-biological interactions.

[117]  L. Goya,et al.  Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). , 2006, The Journal of nutrition.

[118]  Xianglin Shi,et al.  Luteolin inhibits insulin-like growth factor 1 receptor signaling in prostate cancer cells. , 2006, Carcinogenesis.

[119]  A. Bjartell.  Re: Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant , 2006 .

[120]  J. Derisi,et al.  Identification of a Novel Gammaretrovirus in Prostate Tumors of Patients Homozygous for R462Q RNASEL Variant , 2006, PLoS pathogens.

[121]  M. Haghiac,et al.  Quercetin Induces Necrosis and Apoptosis in SCC-9 Oral Cancer Cells , 2005, Nutrition and cancer.

[122]  Yiwei Li,et al.  Regulation of gene expression and inhibition of experimental prostate cancer bone metastasis by dietary genistein. , 2004, Neoplasia.

[123]  C. O'Brian,et al.  Resveratrol Antagonizes EGFR-Dependent Erk1/2 Activation in Human Androgen-Independent Prostate Cancer Cells with Associated Isozyme-Selective PKCα Inhibition , 2004, Investigational New Drugs.

[124]  T. T. Nguyen,et al.  Inhibition of ErbB-2 and ErbB-3 expression by quercetin prevents transforming growth factor alpha (TGF-alpha)- and epidermal growth factor (EGF)-induced human PC-3 prostate cancer cell proliferation. , 2003, International journal of oncology.

[125]  V. Ziboh,et al.  Downregulation of COX-2 and iNOS by amentoflavone and quercetin in A549 human lung adenocarcinoma cell line. , 2002, Prostaglandins, leukotrienes, and essential fatty acids.

[126]  C. Young,et al.  Silymarin inhibits function of the androgen receptor by reducing nuclear localization of the receptor in the human prostate cancer cell line LNCaP. , 2001, Carcinogenesis.

[127]  R. Agarwal,et al.  Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells. , 2000, Cancer research.

[128]  E. Gillanders,et al.  Analysis of HPC1, HPCX, and PCaP in Icelandic hereditary prostate cancer , 2000, Human Genetics.

[129]  G. Iacomino,et al.  Quercetin and anti‐CD95(Fas/Apo1) enhance apoptosis in HPB‐ALL cell line , 1999, FEBS letters.

[130]  R. Weiss.  Herbal Medicine , 1999, Reactions Weekly.

[131]  J. V. van Brussel,et al.  Multidrug Resistance in Prostate Cancer , 1997, Oncology Research and Treatment.

[132]  Farhan Jalees Ahmad,et al.  NANOTECHNOLOGY-BASED STRATEGIES FOR NUTRACEUTICALS: A REVIEW OF CURRENT RESEARCH DEVELOPMENT , 2019, Nanoscience and Technology: An International Journal.

[133]  Shu Yang,et al.  Wnt/Beta-Catenin Signaling and Prostate Cancer Therapy Resistance. , 2019, Advances in experimental medicine and biology.

[134]  K. Sak,et al.  Therapeutic charm of quercetin and its derivatives: a review of research and patents. , 2018, Pharmaceutical patent analyst.

[135]  E. Jabbarzadeh,et al.  The use of natural products to target cancer stem cells. , 2017, American journal of cancer research.

[136]  M. Pichler,et al.  Molecular Pathogenesis of Prostate Cancer , 2017 .

[137]  S. Chikuma.  CTLA-4, an Essential Immune-Checkpoint for T-Cell Activation. , 2017, Current topics in microbiology and immunology.

[138]  Satyapal Singh,et al.  An appraisal of the bioavailability enhancers in Ayurveda in the light of recent pharmacological advances , 2016, Ayu.

[139]  L. Gu,et al.  A review: Using nanoparticles to enhance absorption and bioavailability of phenolic phytochemicals , 2015 .

[140]  H. Inui,et al.  Resveratrol inhibits hypoxia-inducible factor-1α-mediated androgen receptor signaling and represses tumor progression in castration-resistant prostate cancer. , 2014, Journal of nutritional science and vitaminology.

[141]  R. Krishnaswamy,et al.  Quercetin modulates OTA-induced oxidative stress and redox signalling in HepG2 cells - up regulation of Nrf2 expression and down regulation of NF-κB and COX-2. , 2014, Biochimica et biophysica acta.

[142]  T. Seyfried,et al.  On the origin of cancer metastasis. , 2013, Critical reviews in oncogenesis.

[143]  J. A. Ortega-García,et al.  [Constitutional risk factors in prostate cancer]. , 2011, Actas urologicas espanolas.

[144]  M. Debnath,et al.  Phytomedicine: An ancient approach turning into future potential source of therapeutics , 2011 .

[145]  Hsi-Chin Wu,et al.  Association of cyclooxygenase 2 polymorphic genotypes with prostate cancer in taiwan. , 2011, Anticancer research.

[146]  D. Nie,et al.  Quercetin induces apoptosis by activating caspase-3 and regulating Bcl-2 and cyclooxygenase-2 pathways in human HL-60 cells. , 2011, Acta biochimica et biophysica Sinica.

[147]  A. C. Pinto,et al.  A fitoterapia no mundo atual , 2010 .

[148]  Stephen L. Abrams,et al.  Targeting signal transduction pathways to eliminate chemotherapeutic drug resistance and cancer stem cells. , 2010, Advances in enzyme regulation.

[149]  Jen-kun Lin,et al.  Downregulation of androgen receptor expression by luteolin causes inhibition of cell proliferation and induction of apoptosis in human prostate cancer cells and xenografts , 2008, The Prostate.

[150]  H. Nandeesha.  Insulin: a novel agent in the pathogenesis of prostate cancer , 2008, International Urology and Nephrology.

[151]  F. Biering-Sørensen,et al.  Signaling Pathways , 2003 .

[152]  J. Doehmer,et al.  Flavonoids inhibit genetic toxicity produced by carcinogens in cells expressing CYP1A2 and CYP1A1. , 2002, Mutagenesis.

[153]  Robert C. Wolpert,et al.  A Review of the , 1985 .