Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy

Scientific Reports

Volumn 6, Issue , 2016, Pages

  Wu, Chia Hsien ^a   Bai, Li Yuan ^b,c   Tsai, Ming Hsui ^d   Chu, Po Chen ^a,e   Chiu, Chang Fang ^c   Chen, Michael Yuanchien ^c,d   Chiu, Shih Jiuan ^f   Chiang, Jo Hua ^d   Weng, Jing Ru ^d  

^a INSTITUTE OF BIOLOGICAL CHEMISTRY   (Taiwan)

^b CHINA MEDICAL UNIVERSITY   (Taiwan)

^c CHINA MEDICAL UNIVERSITY HOSPITAL   (Taiwan)

^d CHINA MEDICAL UNIVERSITY   (Taiwan)

^e NATIONAL CHENG KUNG UNIVERSITY   (Taiwan)

^f TAIPEI MEDICAL UNIVERSITY   (Taiwan)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; NEUROLEPTIC AGENT; PHENOTHIAZINE DERIVATIVE; REACTIVE OXYGEN METABOLITE; TUMOR MARKER;

ANIMAL; APOPTOSIS; CELL PROLIFERATION; CELL SURVIVAL; DNA DAMAGE; DRUG REPOSITIONING; DRUG SCREENING; GENE EXPRESSION REGULATION; HUMAN; IC50; MALE; METABOLISM; MOUSE; MOUTH TUMOR; NUDE MOUSE; PHOSPHORYLATION; STRUCTURE ACTIVITY RELATION; TUMOR CELL LINE;

ANIMALS; ANTINEOPLASTIC AGENTS; ANTIPSYCHOTIC AGENTS; APOPTOSIS; BIOMARKERS, TUMOR; CELL LINE, TUMOR; CELL PROLIFERATION; CELL SURVIVAL; DNA DAMAGE; DRUG REPOSITIONING; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; INHIBITORY CONCENTRATION 50; MALE; MICE; MICE, NUDE; MOUTH NEOPLASMS; PHENOTHIAZINES; PHOSPHORYLATION; REACTIVE OXYGEN SPECIES; STRUCTURE-ACTIVITY RELATIONSHIP; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84974555439     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep27540     Document Type: Article

References (42)

1. Argiris, A., Karamouzis, M. V., Raben, D., Ferris, R. L. Head and neck cancer. Lancet 371, 1695-1709 (2008).
2. Belcher, R., Hayes, K., Fedewa, S., Chen, A. Y. Current treatment of head and neck squamous cell cancer. J Surg Oncol 110, 551-574 (2014).
3. Ohlow, M. J., Moosmann, B. Phenothiazine: the seven lives of pharmacology's first lead structure. Drug Discov Today 16, 119-131 (2011).
4. Jaszczyszyn, A. et al. Chemical structure of phenothiazines and their biological activity. Pharmacol Rep 64, 16-23 (2012).
5. Sudeshna, G., Parimal, K. Multiple non-psychiatric effects of phenothiazines: a review. Eur J Pharmacol 648, 6-14 (2010).
6. Motohashi, N., Kawase, M., Satoh, K., Sakagami, H. Cytotoxic potential of phenothiazines. Curr Drug Targets 7, 1055-1066 (2006).
7. Gutierrez, A. et al. Phenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia. J Clin Invest 124, 644-655 (2014).
8. Belei, D. et al. New farnesyltransferase inhibitors in the phenothiazine series. Bioorg Med Chem Lett 22, 4517-4522 (2012).
9. Prinz, H. et al. N-benzoylated phenoxazines and phenothiazines: synthesis, antiproliferative activity, and inhibition of tubulin polymerization. J Med Chem 54, 4247-4263 (2011).
10. Abuhaie, C. M. et al. Synthesis and anticancer activity of analogues of phenstatin, with a phenothiazine A-ring, as a new class of microtubule-targeting agents. Bioorg Med Chem Lett 23, 147-152 (2013).
11. Verones, V. et al. Synthesis, antiproliferative activity and tubulin targeting effect of acridinone and dioxophenothiazine derivatives. Eur J Med Chem 59, 39-47 (2013).
12. Shin, S. Y. et al. Induction of early growth response-1 gene expression by calmodulin antagonist trifluoperazine through the activation of Elk-1 in human fibrosarcoma HT1080 cells. J Biol Chem 276, 7797-7805 (2001).
13. Pulkoski-Gross, A. et al. Repurposing the antipsychotic trifluoperazine as an antimetastasis agent. Mol Pharmacol 87, 501-512 (2015).
14. Gangopadhyay, S., Karmakar, P., Dasgupta, U., Chakraborty, A. Trifluoperazine stimulates ionizing radiation induced cell killing through inhibition of DNA repair. Mutat Res 633, 117-125 (2007).
15. Zong, D., Haag, P., Yakymovych, I., Lewensohn, R., Viktorsson, K. Chemosensitization by phenothiazines in human lung cancer cells: impaired resolution of gammaH2AX and increased oxidative stress elicit apoptosis associated with lysosomal expansion and intense vacuolation. Cell Death Dis 2, e181 (2011).
16. Lau, A. T., Wang, Y., Chiu, J. F. Reactive oxygen species: current knowledge and applications in cancer research and therapeutic. J Cell Biochem 104, 657-667 (2008).
17. Visconti, R., Grieco, D. New insights on oxidative stress in cancer. Curr Opin Drug Discov Devel 12, 240-245 (2009).
18. Zafarullah, M., Li, W. Q., Sylvester, J., Ahmad, M. Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 60, 6-20 (2003).
19. Banin, S. et al. Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science 281, 1674-1677 (1998).
20. Pilch, D. R. et al. Characteristics of gamma-H2AX foci at DNA double-strand breaks sites. Biochem Cell Biol 81, 123-129 (2003).
21. Zhang, L. et al. Small molecule regulators of autophagy identified by an image-based high-throughput screen. Proc Natl Acad Sci USA 104, 19023-19028 (2007).
22. Zalckvar, E. et al. A systems level strategy for analyzing the cell death network: implication in exploring the apoptosis/autophagy connection. Cell Death Differ 17, 1244-1253 (2010).
23. Pyo, J. O., Nah, J., Jung, Y. K. Molecules and their functions in autophagy. Exp Mol Med 44, 73-80 (2012).
24. Puissant, A., Robert, G., Auberger, P. Targeting autophagy to fight hematopoietic malignancies. Cell Cycle 9, 3470-3478 (2010).
25. Caporuscio, F., Tafi, A. Pharmacophore modelling: a forty year old approach and its modern synergies. Curr Med Chem 18, 2543-2553 (2011).
26. Ivanov, A. I. Pharmacological inhibitors of exocytosis and endocytosis: novel bullets for old targets. Methods Mol Biol 1174, 3-18 (2014).
27. Munshi, H. G. et al. Differential regulation of membrane type 1-matrix metalloproteinase activity by ERK 1/2-and p38 MAPKmodulated tissue inhibitor of metalloproteinases 2 expression controls transforming growth factor-beta1-induced pericellular collagenolysis. J Biol Chem 279, 39042-39050 (2004).
28. Yang, J. S., Lin, C. W., Hsin, C. H., Hsieh, M. J., Chang, Y. C. Selaginellatamariscina attenuates metastasis via Akt pathways in oral cancer cells. PLoS One 8, e68035 (2013).
29. Wang, H. et al. Downregulation of FAP suppresses cell proliferation and metastasis through PTEN/PI3K/AKT and Ras-ERK signaling in oral squamous cell carcinoma. Cell Death Dis 5, e1155 (2014).
30. Chen, C. L., Chi, C. W., Liu, T. Y. Hydroxyl radical formation and oxidative DNA damage induced by areca quid in vivo. J Toxicol Environ Health A 65, 327-336 (2002).
31. Chang, L. Y. et al. Areca nut extracts increased the expression of cyclooxygenase-2, prostaglandin E2 and interleukin-1alpha in human immune cells via oxidative stress. Arch Oral Biol 58, 1523-1531 (2013).
32. Huo, W., Li, Z. M., Pan, X. Y., Bao, Y. M., An, L. J. Antioxidant enzyme levels in pathogenesis of oral squamous cell carcinoma (OSCC). Drug Res (Stuttg) 64, 629-632 (2014).
33. Liu, S., Han, Y., Zhang, T., Yang, Z. Protective effect of trifluoperazine on hydrogen peroxide-induced apoptosis in PC12 cells. Brain Res Bull 84, 183-188 (2011).
34. Polischouk, A. G. et al. The antipsychotic drug trifluoperazine inhibits DNA repair and sensitizes non small cell lung carcinoma cells to DNA double-strand break induced cell death. Mol Cancer Ther 6, 2303-2309 (2007).
35. Suman, S. et al. The pro-apoptotic role of autophagy in breast cancer. Br J Cancer 111, 309-317 (2014).
36. Wang, Z., Zhu, S., Zhang, G., Liu, S. Inhibition of autophagy enhances the anticancer activity of bortezomib in B-cell acute lymphoblastic leukemia cells. Am J Cancer Res 5, 639-650 (2015).
37. Hollerhage, M. et al. Trifluoperazine rescues human dopaminergic cells from wild-type alpha-synuclein-induced toxicity. Neurobiol Aging 35, 1700-1711 (2014).
38. Rehman, G., Shehzad, A., Khan, A. L., Hamayun, M. Role of AMP-activated protein kinase in cancer therapy. Arch Pharm (Weinheim) 347, 457-468 (2014).
39. Bai, L. Y., Lin, W. Y., Chiu, C. F., Weng, J. R. Anti-tumor activities of triterpenes from Syzygium kusukusense. Nat Prod Commun 9, 1557-1558 (2014).
40. Bai, L. Y. et al. OSU-A9, an indole-3-carbinol derivative, induces cytotoxicity in acute myeloid leukemia through reactive oxygen species-mediated apoptosis. Biochem Pharmacol 86, 1430-1440 (2013).
41. Bai, L. Y. et al. Alphitolic acid, an anti-inflammatory triterpene, induces apoptosis and autophagy in oral squamous cell carcinoma cells, in part, through a p53-dependent pathway. J Funct Foods 18, 368-378 (2015).
42. Bai, L. Y. et al. A triterpenoid from wild bitter gourd inhibits breast cancer cells. Sci Rep 6, 22419, doi: 10.1038/srep22419 (2016).