Celastrol from Tripterygium wilfordii Hook new therapeutic agent for prostate cancer

Tuesday, 08/05/2012  |   Prostate Cancer  |  no comments

Friday, 10 June 2011. Posted in CANCER THUNDER OF GOD VINE An example of natural chemicals is Thunder of God Vine (Tripterygium wilfordii Hook), from which scientist have obtained an active constituent, a triterpene extracted from the plant that has shown important anti-cancer properties, Celastrol. Tripterygium wilfordii for cancer treatment seems to be this way another possible option in the search of active constituents from plants for the treatment of cancer. TRIPTERYGIUM WILFORDII HOOK ANTI-INFLAMMATORY PROPERTIES The most commonly and extended use of Tripterygium wilfordii Hook refers to its anti-inflammatory properties. In Chinese traditional herbal remedies Tripterygium wilfordii Hook was commonly used for these well known anti-inflammatory properties to treat a variety of autoimmune and inflammatory diseases, however and nowadays the discovery of certain anti-cancer properties on some active constituents of Tripterygium wilfordii Hook, as the diterpenoid epoxide triptolide and the quinone triterpene celastrol opened the door to new drugs that can help on the fight against cancer. Both compounds are the subject of multiple clinical and scientific studies on the search for new anti-cancer agents that may help developing new effective anti-carcinogenic drugs. HOW DOES TRIPTERYGIUM WILFORDII HOOK FIGHT CANCER? Before we enter into details on how Celastrol from Tripterygium Wilfordii works performing its anti-cancer function, we need to explain a little bit more some points. The anti-cancer properties exerted by Tripterygium Wilfordii are directly related with a protein present in the human body, the P53. P53 is a tumor suppressor protein that plays a very important role in the fight against cancer. The protein P53 regulates the cell life cycle, telling the body cell when it has come its time to die (this process is known by scientists as apoptosis or programmed cell death -see video below-), thus preventing the uncontrolled cell growth, a disease everyone knows by its most common and scary name, cancer. CELASTROL AND THE PROTEIN P53 Why is Celastrol so important and what is the link with P53 protein? To answer that we first have to understand what is a proteasome inhibitor, because that’s what Celastrol is, a proteasome inhibitor. A proteasome inhibitor is a drug that blocks the action of proteasomes [7], something that breaks down proteins, as our P53 cancer inhibitor protein. So without proteasomes the P53 is safe and sound, being able to continue its natural cancer inhibition role, telling our damaged cells when it has come their time to die. TRIPTERYGIUM WILFORDII HOOK IN TRADITIONAL CHINESE MEDICINE In spite Tripterygium wilfordii hook was originally used in traditional Chinese medicine as a natural anti-inflammatory herbal remedy, in 2006 this active constituent, Celastrol, was studied for its anticancer properties, as it showed to be able to induce leukemia cell apoptosis (programmed cell death) [1]. In some studies in vivo using animal tumor tissue samples showed inhibition of the proteasomal activity and induction of apoptosis in human prostate cancer 26S cells after using Celastrol, demonstrating its potential use as a new anti-cancer agent[1]. CELASTROL AND COLON CANCER, PANCREATIC CANCER AND SQUAMOUS CELL CARCINOMA Celastrol showed also certain anti-cancer properties for the treatment of colon cancer, squamous cell carcinoma and pancreatic cancer cells [6], showing its potential in suppressing invasion and metastasis of cancer cells. Last but not least, in July 2011, the Department of Biology and Molecular Biology from Montclair State University, started to show a certain interest in Triptolide, another extract from the herb Tripterygium wilfordii Hook that apparently is able to activates the p53 pathway to trigger apoptosis in human breast cancer cell lines. References: [1] Celastrol, a triterpene extracted from

the Chinese “Thunder of God Vine,” is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. Yang H, Chen D, Cui QC, Yuan X, Dou QP. The Prevention Program, Barbara Ann Karmanos Cancer Institute, and Department of Pathology, School of Medicine, Wayne State University, Detroit, Michigan 48201, USA. [2] Celastrol targets mitochondrial respiratory chain complex I to induce reactive oxygen species-dependent cytotoxicity in tumor cells. Chen G, Zhang X, Zhao M, Wang Y, Cheng X, Wang D, Xu Y, Du Z, Yu X. [3] Celastrol induces apoptosis in non-small-cell lung cancer A549 cells through activation of mitochondria- and Fas/FasL-mediated pathways. Mou H, Zheng Y, Zhao P, Bao H, Fang W, Xu N. Department of Medical Oncology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang Province 310003, People’s Republic of China. [3] Celastrus-derived celastrol suppresses autoimmune arthritis by modulating antigen-induced cellular and humoral effector responses. Venkatesha SH, Yu H, Rajaiah R, Tong L, Moudgil KD. Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. [4] Inhibitory action of Celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1? pathway. Huang L, Zhang Z, Zhang S, Ren J, Zhang R, Zeng H, Li Q, Wu G. Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China. [5] Natural proteasome inhibitor celastrol suppresses androgen-independent prostate cancer progression by modulating apoptotic proteins and NF-kappaB. Dai Y, Desano J, Tang W, Meng X, Meng Y, Burstein E, Lawrence TS, Xu L. Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America. [6] Celastrol suppresses invasion of colon and pancreatic cancer cells through the downregulation of expression of CXCR4 chemokine receptor. Yadav VR, Sung B, Prasad S, Kannappan R, Cho SG, Liu M, Chaturvedi MM, Aggarwal BB. Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. [7] Wikipedia [8] Does triptolide induce lysosomal-mediated apoptosis in human breast cancer cells? Messina ME Jr, Halaby R. Montclair State University, Department of Biology and Molecular Biology, 1 Normal Avenue, Montclair, NJ 07043, United States [9] Benefit of an extract of Tripterygium Wilfordii Hook F in patients with rheumatoid arthritis: a double-blind, placebo-controlled study. Tao X, Younger J, Fan FZ, Wang B, Lipsky PE. Autoimmunity Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, NIH, Bethesda, Maryland 20892, USA.

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