title: Natural compound Alternol induces oxidative stress-dependent apoptotic cell death preferentially in prostate cancer cells.
abstract: Prostate cancers at the late stage of castration resistance are not responding well to most of current therapies available in clinic, reflecting a desperate need of novel treatment for this life-threatening disease. In this study, we evaluated the anticancer effect of a recently isolated natural compound, Alternol, in multiple prostate cancer cell lines with the properties of advanced prostate cancers in comparison to prostate-derived nonmalignant cells. As assessed by trypan blue exclusion assay, significant cell death was observed in all prostate cancer cell lines except DU145 but not in nonmalignant (RWPE-1 and BPH1) cells. Further analyses revealed that Alternol-induced cell death was an apoptotic response in a dose- and time-dependent manner, as evidenced by the appearance of apoptosis hallmarks such as caspase-3 processing and PARP cleavage. Interestingly, Alternol-induced cell death was completely abolished by reactive oxygen species scavengers N-acetylcysteine and dihydrolipoic acid. We also demonstrated that the proapoptotic Bax protein was activated after Alternol treatment and was critical for Alternol-induced apoptosis. Animal xenograft experiments in nude mice showed that Alternol treatment largely suppressed tumor growth of PC-3 xenografts but not Bax-null DU-145 xenografts in vivo. These data suggest that Alternol might serve as a novel anticancer agent for patients with late-stage prostate cancer.
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, KansasAuthors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Yuzhe
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Ruibao
authors.initials: R
authors.lastname: Chen
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Guodong
authors.initials: G
authors.lastname: Li
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, KansasAuthors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Yiling
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Jiepeng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Lili
authors.initials: L
authors.lastname: Duan
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: Bao-Ting
authors.initials: BT
authors.lastname: Zhu
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas.
authors.forename: J Brantley
authors.initials: JB
authors.lastname: Thrasher
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas bli@kumc.edu xzhang@foxmail.com.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Authors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, KansasAuthors' Affiliations: Department of Urology, Military Postgraduate Medical College, Chinese People's Liberation Army General Hospital, Beijing, China; Department of Urology, The University of Kansas Medical Center, Kansas City, Kansas; Department of Pharmacology, Three Gorges University College of Medicine, Yichang, China; Strand Biotechnology Institute of Research, Shantou, China; Department of Pharmacology & Toxicology, The University of Kansas Medical Center, Kansas City, Kansas bli@kumc.edu xzhang@foxmail.com.
authors.forename: Benyi
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006576:Heterocyclic Compounds, 4 or More Rings / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C526095:Alternol; D006576:Heterocyclic Compounds, 4 or More Rings; D017382:Reactive Oxygen Species; D053148:Caspase 3