Molecular evidence of cryptotanshinone for treatment and prevention of human cancer.

Cryptotanshinone is one of the major tanshinones isolated from the roots of the plant Salvia miltiorrhiza Bunge (Danshen). Danshen has been widely used in traditional Chinese medicine for treatment of a variety of diseases, including coronary artery disease, acute ischemic stroke, hyperlipidemia, chronic renal failure, chronic hepatitis, and Alzheimer's disease, showing no serious adverse effects. Recent studies have shown that cryptotanshinone not only possesses the potential for treatment and prevention of the above-mentioned diseases, but also is a potent anticancer agent. Here we briefly summarize the physical and chemical properties and the pharmacokinetic profiles of cryptotanshinone, and then comprehensively review its anticancer activities as well as the underlying mechanisms.

[1]  G. Blackburn,et al.  Bioactive tanshinones in Salvia miltiorrhiza inhibit the growth of prostate cancer cells in vitro and in mice , 2011, International journal of cancer.

[2]  L. Gu,et al.  Pharmacokinetic characterization of hydroxylpropyl-β-cyclodextrin-included complex of cryptotanshinone, an investigational cardiovascular drug purified from Danshen (Salvia miltiorrhiza) , 2008 .

[3]  H. Weiss,et al.  mTORC1 and mTORC2 regulate EMT, motility, and metastasis of colorectal cancer via RhoA and Rac1 signaling pathways. , 2011, Cancer research.

[4]  T. Byzova,et al.  Oxidation as “The Stress of Life” , 2011, Aging.

[5]  Y. Odaka,et al.  Rapamycin inhibits lymphatic endothelial cell tube formation by downregulating vascular endothelial growth factor receptor 3 protein expression. , 2012, Neoplasia.

[6]  T. Cheng Cardiovascular effects of Danshen. , 2007, International journal of cardiology.

[7]  G. Filomeni,et al.  trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways , 2007, Genes & Nutrition.

[8]  P. Hoff,et al.  Bevacizumab: overview of the literature , 2012, Expert review of anticancer therapy.

[9]  H. Katayama,et al.  Aurora kinase inhibitors as anticancer molecules. , 2010, Biochimica et biophysica acta.

[10]  W. Chan,et al.  Curcumin Inhibits ROS Formation and Apoptosis in Methylglyoxal‐Treated Human Hepatoma G2 Cells , 2005, Annals of the New York Academy of Sciences.

[11]  M. Don,et al.  Cryptotanshinone inhibits macrophage migration by impeding F-actin polymerization and filopodia extension. , 2007, Life sciences.

[12]  Zhiguang Sun,et al.  Cryptotanshinone has diverse effects on cell cycle events in melanoma cell lines with different metastatic capacity , 2011, Cancer Chemotherapy and Pharmacology.

[13]  K. Alitalo,et al.  Lymphangiogenesis: Molecular Mechanisms and Future Promise , 2010, Cell.

[14]  K. O'Byrne,et al.  Targeting oxidative stress in cancer , 2010, Expert opinion on therapeutic targets.

[15]  J. Turkson,et al.  Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression. , 2001, The Journal of clinical investigation.

[16]  B. Tan,et al.  Salvia miltiorrhiza and ischemic diseases. , 2000, Acta pharmacologica Sinica.

[17]  V. Hwa,et al.  Interferon-gamma-induced dephosphorylation of STAT3 and apoptosis are dependent on the mTOR pathway. , 2006, Experimental cell research.

[18]  K. Fizazi,et al.  Targeting Continued Androgen Receptor Signaling in Prostate Cancer , 2011, Clinical Cancer Research.

[19]  L. V. Van Gaal,et al.  Human obesity: from lipid abnormalities to lipid oxidation. , 1995, International journal of obesity and related metabolic disorders : journal of the International Association for the Study of Obesity.

[20]  Wenhua Zheng,et al.  Cryptotanshinone protects primary rat cortical neurons from glutamate-induced neurotoxicity via the activation of the phosphatidylinositol 3-kinase/Akt signaling pathway , 2009, Experimental Brain Research.

[21]  Xie Mz,et al.  [Absorption, distribution, excretion and metabolism of cryptotanshinone]. , 1983 .

[22]  D. Sabatini,et al.  mTOR Signaling in Growth Control and Disease , 2012, Cell.

[23]  Faisal T Thayyullathil,et al.  Rapid reactive oxygen species (ROS) generation induced by curcumin leads to caspase-dependent and -independent apoptosis in L929 cells. , 2008, Free radical biology & medicine.

[24]  Steven P. Gygi,et al.  mTOR and S6K1 Mediate Assembly of the Translation Preinitiation Complex through Dynamic Protein Interchange and Ordered Phosphorylation Events , 2005, Cell.

[25]  J. Margolick,et al.  Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance , 2007, Proceedings of the National Academy of Sciences.

[26]  P. Hu,et al.  Quality assessment of radix salviae miltiorrhizae. , 2005, Chemical & pharmaceutical bulletin.

[27]  J. Folkman Angiogenesis in cancer, vascular, rheumatoid and other disease , 1995, Nature Medicine.

[28]  Chawnshang Chang,et al.  Cryptotanshinone down‐regulates androgen receptor signaling by modulating lysine‐specific demethylase 1 function , 2012, International journal of cancer.

[29]  R. Ji Lymphatic endothelial cells, tumor lymphangiogenesis and metastasis: New insights into intratumoral and peritumoral lymphatics , 2006, Cancer and Metastasis Reviews.

[30]  Alexander Nürnberg,et al.  Nucleating actin for invasion , 2011, Nature Reviews Cancer.

[31]  M. Don,et al.  Cryptotanshinone inhibits chemotactic migration in macrophages through negative regulation of the PI3K signaling pathway , 2007, British journal of pharmacology.

[32]  Hua Yu,et al.  STATs in cancer inflammation and immunity: a leading role for STAT3 , 2009, Nature Reviews Cancer.

[33]  S. Yeh,et al.  Cryptotanshinone suppresses androgen receptor-mediated growth in androgen dependent and castration resistant prostate cancer cells. , 2012, Cancer letters.

[34]  S. Desrivières,et al.  Rapamycin Inhibition of the G1 to S Transition Is Mediated by Effects on Cyclin D1 mRNA and Protein Stability* , 1998, The Journal of Biological Chemistry.

[35]  M. Huang,et al.  A Mechanistic Study of the Intestinal Absorption of Cryptotanshinone, the Major Active Constituent of Salvia miltiorrhiza , 2006, Journal of Pharmacology and Experimental Therapeutics.

[36]  J. Avruch,et al.  Serine phosphorylation and maximal activation of STAT3 during CNTF signaling is mediated by the rapamycin target mTOR , 2000, Current Biology.

[37]  D. Carey,et al.  Rapamycin suppresses experimental aortic aneurysm growth. , 2004, Journal of vascular surgery.

[38]  Baoshan Xu,et al.  Rapamycin Inhibits Cytoskeleton Reorganization and Cell Motility by Suppressing RhoA Expression and Activity* , 2010, The Journal of Biological Chemistry.

[39]  P. Polak,et al.  mTOR and the control of whole body metabolism. , 2009, Current opinion in cell biology.

[40]  I. Cho,et al.  Resveratrol Protects Mitochondria against Oxidative Stress through AMP-Activated Protein Kinase-Mediated Glycogen Synthase Kinase-3β Inhibition Downstream of Poly(ADP-ribose)polymerase-LKB1 Pathway , 2009, Molecular Pharmacology.

[41]  H. Kuang,et al.  Cryptotanshinone reverses reproductive and metabolic disturbances in prenatally androgenized rats via regulation of ovarian signaling mechanisms and androgen synthesis. , 2011, American journal of physiology. Regulatory, integrative and comparative physiology.

[42]  Yan Luo,et al.  Cryptotanshinone Inhibits Lymphatic Endothelial Cell Tube Formation by Suppressing VEGFR-3/ERK and Small GTPase Pathways , 2011, Cancer Prevention Research.

[43]  I. Kang,et al.  Cryptotanshinone induces ER stress-mediated apoptosis in HepG2 and MCF7 cells , 2011, Apoptosis.

[44]  M. Chancellor,et al.  Antioxidant effects of green tea and its polyphenols on bladder cells. , 2008, Life sciences.

[45]  Kedi Xu,et al.  Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway. , 2009, Oncology reports.

[46]  Z. Hu,et al.  Reversed-phase liquid chromatographic determination of cryptotanshinone and its active metabolite in pig plasma and urine. , 1999, Journal of pharmaceutical and biomedical analysis.

[47]  Hongyuan Chen,et al.  Effects of the coexisting diterpenoid tanshinones on the pharmacokinetics of cryptotanshinone and tanshinone IIA in rat. , 2007, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[48]  D. Guo,et al.  Microbial biotransformation of cryptotanshinone by Cunninghamella elegans and its application for metabolite identification in rat bile , 2009, Journal of Asian natural products research.

[49]  Xiao-xin Zhu,et al.  [Advances in study of the pharmacological effects of danshen on hemorheology]. , 2005, Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica.

[50]  D. Han,et al.  Cryptotanshinone inhibits constitutive signal transducer and activator of transcription 3 function through blocking the dimerization in DU145 prostate cancer cells. , 2009, Cancer research.

[51]  G. Perry,et al.  Oxidative stress in Alzheimer disease: A possibility for prevention , 2010, Neuropharmacology.

[52]  A. Joe,et al.  Stat3 orchestrates tumor development and progression: the Achilles' heel of head and neck cancers? , 2010, Current cancer drug targets.

[53]  S. Pastore,et al.  Plant polyphenols and tumors: from mechanisms to therapies, prevention, and protection against toxicity of anti-cancer treatments. , 2009, Current medicinal chemistry.

[54]  Hee-Jung Choi,et al.  Cryptotanshinone from Salvia miltiorrhiza BUNGE has an inhibitory effect on TNF-alpha-induced matrix metalloproteinase-9 production and HASMC migration via down-regulated NF-kappaB and AP-1. , 2006, Biochemical pharmacology.

[55]  J. Ha,et al.  Antidiabetes and Antiobesity Effect of Cryptotanshinone via Activation of AMP-Activated Protein Kinase , 2007, Molecular Pharmacology.

[56]  Mohammad Saleem,et al.  Disruption of Androgen and Estrogen Receptor Activity in Prostate Cancer by a Novel Dietary Diterpene Carnosol: Implications for Chemoprevention , 2010, Cancer Prevention Research.

[57]  D. Sohn,et al.  PF2401-SF, standardized fraction of Salvia miltiorrhiza and its constituents, tanshinone I, tanshinone IIA, and cryptotanshinone, protect primary cultured rat hepatocytes from bile acid-induced apoptosis by inhibiting JNK phosphorylation. , 2007, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[58]  Zhong Zuo,et al.  Danshen: An Overview of Its Chemistry, Pharmacology, Pharmacokinetics, and Clinical Use , 2005, Journal of clinical pharmacology.

[59]  G. Feldman,et al.  Inhibition of STAT3 signaling induces apoptosis and decreases survivin expression in primary effusion lymphoma. , 2003, Blood.

[60]  Y. M. Kim,et al.  Cryptotanshinone, a lipophilic compound of Salvia miltiorrriza root, inhibits TNF-alpha-induced expression of adhesion molecules in HUVEC and attenuates rat myocardial ischemia/reperfusion injury in vivo. , 2009, European journal of pharmacology.

[61]  Hongyu Zhou,et al.  Role of mTOR signaling in tumor cell motility, invasion and metastasis. , 2011, Current protein & peptide science.

[62]  L. Platanias,et al.  CCL5-mediated T-cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1. , 2008, Blood.

[63]  Young-Soo Hong,et al.  Abietane diterpenes from Salvia miltiorrhiza inhibit the activation of hypoxia-inducible factor-1. , 2007, Journal of natural products.

[64]  H. Kwon,et al.  Cryptotanshinone but not tanshinone IIA inhibits angiogenesis in vitro , 2005, Experimental & Molecular Medicine.

[65]  B. Dörken,et al.  A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein {beta} and NF-{kappa}B activity in Hodgkin and anaplastic large cell lymphomas. , 2005, Blood.

[66]  Xiuzhen Han,et al.  Cryptotanshinone Inhibits Cancer Cell Proliferation by Suppressing Mammalian Target of Rapamycin–Mediated Cyclin D1 Expression and Rb Phosphorylation , 2010, Cancer Prevention Research.

[67]  Masanori Arita,et al.  Databases on food phytochemicals and their health-promoting effects. , 2011, Journal of agricultural and food chemistry.

[68]  Yu-jin Jeong,et al.  (-)Epigallocatechin gallate and quercetin enhance survival signaling in response to oxidant-induced human endothelial apoptosis. , 2005, The Journal of nutrition.

[69]  Dong Hwan Sohn,et al.  Preventive effects of a purified extract isolated from Salvia miltiorrhiza enriched with tanshinone I, tanshinone IIA and cryptotanshinone on hepatocyte injury in vitro and in vivo. , 2009, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[70]  Y. Odaka,et al.  Cryptotanshinone Activates p38/JNK and Inhibits Erk1/2 Leading to Caspase-Independent Cell Death in Tumor Cells , 2012, Cancer Prevention Research.