Research in her laboratory is focused on understanding the molecular mechanisms of action of natural products for cancer prevention and therapy by targeting the proteolysis pathway. The discovery of the ubiqutin-proteasome system opens up a new way for cancer therapy. Using the proteasome as a ligand, several traditional Chinese medicinal compounds have been found to bind and inhibit the proteasome beta5 subunit by in silico docking screening, which proteasome inhibitory activities and anti-tumor effects have been verified in prostate cancer cells and human prostate cancer xenografts in nude mice. The proteasome inhibitors are able to induce cell cycle arrest and trigger apoptotic cell death in human prostate cancer through accumulation of the cyclin-dependent kinase inhibitors p21 or p27, and pro- apoptotic proteins such as Bax. Protein degradation mainly depends on the ubiquitin-proteasome system and autophagy lysosome pathway, which are believed to cross-link with each other. Currently her lab is interested in understanding the role of transcription factors or miRNAs in the regulation of proteasome inhibitor induced autophagy. Other studies are directed toward elucidating the role of chemopreventive agents in sensitization of cancer cells to conventional therapeutics. KEY PUBLICATIONS: (* corresponding author) Yang H, Wang Y, Cheryan VT, Wu W, Cui CQ, Polin LA, Pass HI, Dou QP, Rishi AK, Wali A. Withaferin a inhibits the proteasome activity i n mesothelioma i n vitro and i n vivo. PLoS One. 2012;7(8):e41214. Epub 2012 Aug 17. Frezza M, Yang H, Dou QP. Modulation of the tumor cell death pathway by androgen receptor i n response to cytotoxic stimuli. J Cell Physiol. 2011 Nov. 226(11):2731-9. Chen D, Wan SB, Yang H, Chan TH, Dou QP. EGCG , green tea polyphenols and their synthetic analogs and prodrugs for human cancer prevention and treatment. Adv Clin Chem 2011 53:155-77. Yang H*, Lanbis-Piwowar K, Chan TH, Dou QP. Green tea polyphenols as proteasome inhibitors: implication i n chmoprevetion. Curr Cancer Drug Targets 2011 Mar;11(3):296-306. Kanwar J, Mohammad I, Yang H, Huo C, Chan TH, Dou QP. Computational modeling of the potential interactions of the proteasome beta5 subunit and catechol-O-methyltransferase-resistant EGCG analogs. Int J Mol Med 2010 Aug;26(2):209-15. Yang H and Dou QP. Targeting Apoptosis Pathway with Natural Terpenoids: Implications for Treatment of Breast and Prostate Cancer (invited review). Current Drug Targets, 2010, 11(6):734-44. Yang H, Liu J, Dou QP. Targeting tumor proteasome with traditional Chinese medicine. Curr Drug Discov Technol. 2010 Mar 1;7(1):46-53. Huo C#, Yang H#, Cui QC, Dou QP, Chan TH. Proteasome inhibition i n human breast cancer cells with high catechol-O-methyltransferase activity by green tea polyphenol EGCG analogs. Bioorg Med Chem. 2010 Feb;18(3):1252-8. Epub 2009 Dec 16. Wang Y, Rishi AK, Puliyappadamba VT, Sharma S, Yang H, Tarca A, Ping Dou Q, Lonardo F, Ruckdeschel JC, Pass HI, Wali A. Targeted proteasome inhibition by velcade induces apoptosis i n human mesothelioma and breast cancer cell lines. Cancer Chemother Pharmacol. 2009, 66(3):455-66. Yang H, Sun DK, Chen D, Cui QC, Gu YY, Jiang T, Chen W, Wan SB, Dou QP. Antitumor activity of novel fluoro-substituted (-)-epigallocatechin-3-gallate analogs. Cancer Lett. 2010, 292(1):48-53. Padhye S, Yang H, Jamadar A, Cui QC, Chavan D, Dominiak K, McKinney J, Banerjee S, Dou QP, Sarkar FH. New Difluoro Knoevenagel Condensates of Curcumin, Their Schiff Bases and Copper Complexes as Proteasome Inhibitors and Apoptosis Inducers i n Cancer Cells. Pharm Res. 2009 Aug;26(8):1874-80. Yang H, Zonder JA, Dou QP. Clinical development of novel proteasome inhibitors for cancer treatment. Expert Opin Investig Drugs. 2009 Jul;18(7):957-71. Yang H, Zhou P, Huang H, Chen D, Ma N, Cui QC, Shen S, Dong W, Zhang X, Lian W, Wang X, Dou QP and Liu J. Shikonin exerts antitumor activity via proteasome inhibition and cell death induction i n vitro and i n vivo. Int J Cancer. 2009 May 15;124(10):2450-9. (Cover story). Yang H, Murthy S, Sarkar FH, Sheng S, Reddy GP and Dou QP. Calpain-mediated androgen receptor breakdown i n apoptotic prostate cancer cells. J Cell Physiol. 2008 Dec;217(3):569-576. Li L, Yang H, Chen D, Cui C and Dou QP. Disulfiram promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity i n human cancer cells. Toxicol Appl Pharmacol. 2008 Jun 1;229(2):206-214. Yang H, Landis-Piwowar KR, Chen D, Milacic V, Dou QP. Natural compounds with proteasome inhibitory activity for cancer prevention and treatment. Curr Protein Pept Sci. 2008 Jun;9(3):227-39. Yang H, Landis-Piwowar KR, Lu D, Yuan Y, Li L, Reddy GP, Yuan X, Dou QP. Pristimerin induces apoptosis by targeting the proteasome i n prostate cancer cells. J Cell Biochem. 2008 Jan 1;103(1):234-44. Li X, Chen D, Yin S, Meng Y, Yang H, Landis-Piwowar KR, Li Y, Sarkar FH, Reddy GP, Dou QP, Sheng S. p38 mitogen-activated protein kinase-dependent Maspin induction positively feeds back on proteasome inhibitor-mediated prostate tumor apoptosis. J Cell Physiol. 2007 Aug;212(2):298-306. Chen D, Cui QC, Yang H, Barrea RA, Sarkar FH, Sheng S, Yan B, Reddy GP, Dou QP. Clioquinol, a therapeutic agent for Alzheimer’s Disease, has proteasome-inhibitory, androgen receptor suppressing, apoptosis-inducing and anti-tumor activities i n human prostate cancer cells and xenografts. Cancer Res. 2007 Feb 15;67(4):1636-44. Chen D, Chen MS, Cui QC, Yang H, Dou QP. Structure-proteasome-inhibitory activity relationships of dietary flavonoids i n human cancer cells. Front Biosci. 2007 Jan 1;12:1935-45. Yang H, Shi G, Dou QP. The Tumor Proteasome Is a Primary Target for the Natural Anticancer Compound Withaferin A Isolated from “Indian Winter Cherry”. Mol Pharmacol. 2007 Feb;71(2):426-37. Epub 2006 Nov 8. Landis-Piwowar KR, Milacic V, Chen D, Yang H, Zhao Y, Chan TH, Yan B, Dou QP. The proteasome as a potential target for novel anticancer drugs and chemosensitizers. Drug Resist Updat. 2006 Dec;9(6):263-73. Epub 2007 Jan 2. Review. Chen D, Cui QC, Yang H, Dou QP. Disulfiram, a clinically used anti-alcoholism drug and copper-binding agent, induces apoptotic cell death i n breast cancer cultures and xenografts via inhibition of the proteasome activity. Cancer Res. 2006 Nov 1;66(21):10425-33. Yang H, Chen D, Cui QC, Yuan X, Dou QP. Celastrol, a triterpene extracted from the Chinese “Thunder of God Vine,” is a potent proteasome inhibitor and suppresses human prostate cancer growth i n nude mice. Cancer Res. 2006 May 1;66(9):4758-65. (Cover Featured) Huanjie Yang, Gen sheng Wu, p53 transactivatesthe phosphatase MKP1 through both intronic and exonic p53 responsive elements. Cancer Biology and Therapy, 2004，3(12) ：1277-1282.
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