Xuan Chen1, Yue Liu2, Jian Wu3, Huarong Huang4, Zhiyun Du4, Kun Zhang4, Daiying Zhou5, Kaylyn Hung2, Susan Goodin6, Xi Zheng7. 1. Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A. 2. Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A. 3. The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, P.R. China. 4. Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China. 5. Guangdong Food and Drug Vocational College, Guangzhou, P.R. China. 6. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, U.S.A. 7. Laboratory of Natural Medicinal Chemistry & Green Chemistry, Guangdong University of Technology, Guangzhou, P.R. China Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, Piscataway, NJ, U.S.A. xizheng@pharmacy.rutgers.edu.
Abstract
AIM: To investigate the effects and mechanisms of docetaxel and atorvastatin administered individually or in combination on prostate cancer cells. MATERIALS AND METHODS: Cell growth and apoptosis were determined by the trypan blue exclusion assay and morphological assessment of cells was performed with propidium iodide. NF-κB activity was determined by luciferase reporter gene assay and the western blot assay was used to determine the levels of Bcl-2, phospho-Akt, VEGF, and phospho-Erk1/2. RESULTS: Results showed that following pre-treatment with cholesterol, resistance of PC-3 prostate cancer cells to docetaxel was increased. The combination of docetaxel with atorvastatin potently inhibited growth and induced apoptosis in PC-3 cells. Mechanistic studies indicated that induction of apoptosis in PC-3 cells was associated with significant decreases in the levels of Bcl-2, VEGF, phosphor-Akt, and phosphor-Erk1/2. CONCLUSION: Treatment with cholesterol decreased the sensitivity of prostate cancer cells to docetaxel. Docetaxel in combination with cholesterol-lowering drugs such as atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer. Copyright
AIM: To investigate the effects and mechanisms of docetaxel and atorvastatin administered individually or in combination on prostate cancer cells. MATERIALS AND METHODS: Cell growth and apoptosis were determined by the trypan blue exclusion assay and morphological assessment of cells was performed with propidium iodide. NF-κB activity was determined by luciferase reporter gene assay and the western blot assay was used to determine the levels of Bcl-2, phospho-Akt, VEGF, and phospho-Erk1/2. RESULTS: Results showed that following pre-treatment with cholesterol, resistance of PC-3prostate cancer cells to docetaxel was increased. The combination of docetaxel with atorvastatin potently inhibited growth and induced apoptosis in PC-3 cells. Mechanistic studies indicated that induction of apoptosis in PC-3 cells was associated with significant decreases in the levels of Bcl-2, VEGF, phosphor-Akt, and phosphor-Erk1/2. CONCLUSION: Treatment with cholesterol decreased the sensitivity of prostate cancer cells to docetaxel. Docetaxel in combination with cholesterol-lowering drugs such as atorvastatin may be an effective strategy for inhibiting the growth of prostate cancer. Copyright
Authors: Sawsan Youssef; Olaf Stüve; Juan C Patarroyo; Pedro J Ruiz; Jennifer L Radosevich; Eun Mi Hur; Manuel Bravo; Dennis J Mitchell; Raymond A Sobel; Lawrence Steinman; Scott S Zamvil Journal: Nature Date: 2002-11-07 Impact factor: 49.962
Authors: Gemma Llaverias; Christiane Danilo; Yu Wang; Agnes K Witkiewicz; Kristin Daumer; Michael P Lisanti; Philippe G Frank Journal: Am J Pathol Date: 2010-11-18 Impact factor: 4.307
Authors: Takayuki Ikezoe; Yasuko Hisatake; Tamotsu Takeuchi; Yuji Ohtsuki; Yang Yang; Jonathan W Said; Hirokuni Taguchi; H Phillip Koeffler Journal: Cancer Res Date: 2004-10-15 Impact factor: 12.701
Authors: Ian F Tannock; Ronald de Wit; William R Berry; Jozsef Horti; Anna Pluzanska; Kim N Chi; Stephane Oudard; Christine Théodore; Nicholas D James; Ingela Turesson; Mark A Rosenthal; Mario A Eisenberger Journal: N Engl J Med Date: 2004-10-07 Impact factor: 91.245
Authors: K L Tedesco; A D Thor; D H Johnson; Y Shyr; K A Blum; L J Goldstein; W J Gradishar; B P Nicholson; D E Merkel; D Murrey; S Edgerton; G W Sledge Journal: J Clin Oncol Date: 2004-03-15 Impact factor: 44.544
Authors: Jacques Ferlay; Isabelle Soerjomataram; Rajesh Dikshit; Sultan Eser; Colin Mathers; Marise Rebelo; Donald Maxwell Parkin; David Forman; Freddie Bray Journal: Int J Cancer Date: 2014-10-09 Impact factor: 7.396
Authors: Hannah M Jones; Ziwei Fang; Wenchuan Sun; Leslie H Clark; Jessica E Stine; Arthur-Quan Tran; Stephanie A Sullivan; Timothy P Gilliam; Chunxiao Zhou; Victoria L Bae-Jump Journal: Am J Cancer Res Date: 2017-12-01 Impact factor: 6.166
Authors: Zhenshi Wang; Lanyue Zhang; Zheng Wan; Yan He; Huarong Huang; Hongping Xiang; Xiaofeng Wu; Kun Zhang; Yang Liu; Susan Goodin; Zhiyun Du; Xi Zheng Journal: Pathol Oncol Res Date: 2018-05-24 Impact factor: 3.201
Authors: Lin Yu; Xiaofeng Wu; Min Chen; Huarong Huang; Yan He; Huaqian Wang; Dongli Li; Zhiyun Du; Kun Zhang; Susan Goodin; Xi Zheng Journal: Int J Med Sci Date: 2017-04-07 Impact factor: 3.738
Authors: Felipe Henriques; Magno A Lopes; Felipe O Franco; Pamela Knobl; Kaltinaitis B Santos; Luana L Bueno; Victor A Correa; Alexander H Bedard; Adilson Guilherme; Alexander Birbrair; Sidney B Peres; Stephen R Farmer; Miguel L Batista Journal: Sci Rep Date: 2018-12-21 Impact factor: 4.379
Authors: Federica Iannelli; Maria Serena Roca; Rita Lombardi; Chiara Ciardiello; Laura Grumetti; Simona De Rienzo; Tania Moccia; Carlo Vitagliano; Angela Sorice; Susan Costantini; Maria Rita Milone; Biagio Pucci; Alessandra Leone; Elena Di Gennaro; Rita Mancini; Gennaro Ciliberto; Francesca Bruzzese; Alfredo Budillon Journal: J Exp Clin Cancer Res Date: 2020-10-08