Proposed cytotoxic mechanisms of the saffron carotenoids crocin and crocetin on cancer cell lines

Biochemistry and Cell Biology

Volumn 92, Issue 2, 2014, Pages 105-111

  Kim, Se Hyeuk ^a   Lee, Jung Min ^b   Kim, Sun Chang ^c   Park, Chan Bae ^b   Lee, Pyung Cheon ^a  

^a Ajou University   (South Korea)

^b Ajou University School of Medicine   (South Korea)

^c Korea Advanced Institute of Science and Technology (KAIST)   (South Korea)

Author keywords

Crocetin; Crocin; LDHA; ROS

Indexed keywords

CELL CULTURE; FLOW CYTOMETRY; FOOD ADDITIVES; PIGMENTS;

CELLULAR REACTIVE OXYGEN SPECIES; CROCETIN; CROCIN; FLUORESCENCE ACTIVATED CELL SORTING; LDHA; NUCLEAR FACTOR ERYTHROID 2-RELATED FACTOR 2; ROS; STRUCTURAL DIFFERENCES;

CYTOTOXICITY;

CROCETIN; CROCIN; LACTATE DEHYDROGENASE; REACTIVE OXYGEN METABOLITE; TRANSCRIPTION FACTOR NRF2;

ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER CELL CULTURE; CELL STRAIN HCT116; CELL STRAIN HEPG2; CONTROLLED STUDY; CROCUS SATIVUS; CYTOTOXICITY; DRUG ISOLATION; DRUG MECHANISM; ENZYME INHIBITION; FEMALE; FLUORESCENCE ACTIVATED CELL SORTING; HELA CELL; HUMAN; HUMAN CELL; IC 50; PROTEIN EXPRESSION; STIGMA; STRUCTURE ACTIVITY RELATION;

CAROTENOIDS; CELL LINE, TUMOR; CROCUS; CYTOTOXINS; FEMALE; HUMANS; ISOENZYMES; L-LACTATE DEHYDROGENASE; NF-E2-RELATED FACTOR 2; REACTIVE OXYGEN SPECIES;

EID: 84898070696     PISSN: 08298211     EISSN: 12086002     Source Type: Journal    
DOI: 10.1139/bcb-2013-0091     Document Type: Article

References (24)

1. Albrecht M. Takaichi S. Steiger S. Wang Z.Y. Sandmann G. 2000. Novel hydroxycarotenoids with improved antioxidative properties produced by gene combination in Escherichia coli. Nat. Biotechnol. 18 (8): 843-846. 10.1038/78443. 10932152.
2. Arseneault R. Chien A. Newington J.T. Rappon T. Harris R. Cumming R.C. 2013. Attenuation of LDHA expression in cancer cells leads to redox-dependent alterations in cytoskeletal structure and cell migration. Cancer Lett. 338 (2): 255-266. 10.1016/j.canlet.2013.03.034. 23583676.
3. Aung H.H Wang C.Z. Ni M. Fishbein A. Mehendale S.R. Xie J.T. et al 2007. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp. Oncol. 29 (3): 175-180. 18004240.
4. Bayley J.P. Devilee P. 2012. The Warburg effect in 2012. Curr. Opin. Oncol. 24 (1): 62-67. 10.1097/CCO.0b013e32834deb9e. 22123234.
5. Ben-Dor A. Steiner M. Gheber L. Danilenko M. Dubi N. Linnewiel K. et al 2005. Carotenoids activate the antioxidant response element transcription system. Mol. Cancer Ther. 4 (1): 177-186. 15657364.
6. Escribano J. Alonso G.L. Coca-Prados M. Fernández J.A. 1996. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett. 100 (1-2): 23-30. 10.1016/0304-3835(95)04067-6. 8620447.
7. Fantin V.R. St-Pierre J. Leder P. 2006. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer Cell, 9 (6): 425-434. 10.1016/j.ccr.2006.04.023. 16766262.
8. Gutheil W.G. Reed G. Ray A. Anant S. Dhar A. 2012. Crocetin: An agent derived from saffron for prevention and therapy for cancer. Curr. Pharm. Biotechnol. 13 (1): 173-179. 10.2174/138920112798868566. 21466430.
9. Holt N.E. Zigmantas D. Valkunas L. Li X.P. Niyogi K.K. Fleming G.R. 2005. Carotenoid cation formation and the regulation of photosynthetic light harvesting. Science, 307 (5708): 433-436. 10.1126/science.1105833. 15662017.
10. Itoh K. Chiba T. Takahashi S. Ishii T. Igarashi K. Katoh Y. et al 1997. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236 (2): 313-322. 10.1006/bbrc.1997.6943. 9240432.
11. Kanakis C.D. Tarantilis P.A. Tajmir-Riahi H.A. Polissiou M.G. 2007 a. Interaction of tRNA with safranal, crocetin, and dimethylcrocetin. J. Biomol. Struct. Dyn. 24 (6): 537-545. 10.1080/07391102.2007.10507142. 17508775.
12. Kanakis C.D. Tarantilis P.A. Tajmir-Riahi H.A. Polissiou M.G. 2007 b. DNA interaction with saffron's secondary metabolites safranal, crocetin, and dimethylcrocetin. DNA Cell Biol. 26 (1): 63-70. 10.1089/dna.2006.0529. 17263598.
13. Lee P.C. Momen A.Z.R. Mijts B.N. Schmidt-Dannert C. 2003. Biosynthesis of structurally novel carotenoids in Escherichia coli. Chem. Biol. 10 (5): 453-462. 10.1016/S1074-5521(03)00103-0. 12770827.
14. Linnewiel K. Ernst H. Caris-Veyrat C. Ben-Dor A. Kampf A. Salman H. et al 2009. Structure activity relationship of carotenoid derivatives in activation of the electrophile/antioxidant response element transcription system. Free Radic. Biol. Med. 47 (5): 659-667. 10.1016/j.freeradbiomed.2009.06.008. 19524036.
15. Mousavi S.H. Moallem S.A. Mehri S. Shahsavand S. Nassirli H. Malaekeh-Nikouei B. 2011. Improvement of cytotoxic and apoptogenic properties of crocin in cancer cell lines by its nanoliposomal form. Pharm. Biol. 49 (10): 1039-1045. 10.3109/13880209.2011.563315. 21936628.
16. Ohta T. Iijima K. Miyamoto M. Nakahara I. Tanaka H. Ohtsuji M. et al 2008. Loss of keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res. 68 (5): 1303-1309. 10.1158/0008-5472.CAN-07- 5003. 18316592.
17. Samarghandian S. Boskabady M.H. Davoodi S. 2010. Use of in vitro assays to assess the potential antiproliferative and cytotoxic effects of saffron (Crocus sativus L.) in human lung cancer cell line. Pharmacogn. Mag. 6 (24): 309-314. 10.4103/0973-1296.71799. 21120034.
18. Sharoni Y. Linnewiel-Hermoni K. Khanin M. Salman H. Veprik A. Danilenko M. Levy J. 2012. Carotenoids and apocarotenoids in cellular signaling related to cancer: A review. Mol. Nutr. Food Res. 56 (2): 259-269. 10.1002/mnfr.201100311. 22102431.
19. Sun J. Xu X.M. Ni C.Z. Zhang H. Li X.Y. Zhang C.L. et al 2011. Crocin inhibits proliferation and nucleic acid synthesis and induces apoptosis in the human tongue squamous cell carcinoma cell line tca8113. Asian Pac. J. Cancer Prev. 12 (10): 2679-2683. 22320974.
20. Surh Y.J. 2003. Cancer chemoprevention with dietary phytochemicals. Nat. Rev. Cancer, 3 (10): 768-780. 10.1038/nrc1189. 14570043.
21. Tavakkol-Afshari J. Brook A. Mousavi S.H. 2008. Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Food Chem. Toxicol. 46 (11): 3443-3447. 10.1016/j.fct.2008.08.018. 18790714.
22. Wang X.J. Sun Z. Villeneuve N.F. Zhang S. Zhao F. Li Y. et al 2008. Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis, 29 (6): 1235-1243. 10.1093/carcin/bgn095. 18413364.
23. Wyss A. 2004. Carotene oxygenases: A new family of double bond cleavage enzymes. J. Nutr. 134 (1): 246S-250S. 14704328.
24. Zhou M. Zhao Y. Ding Y. Liu H. Liu Z. Fodstad O. et al 2010. Warburg effect in chemosensitivity: Targeting lactate dehydrogenase-A re-sensitizes Taxol-resistant cancer cells to taxol. Mol. Cancer, 9 (1): 33. 10.1186/1476-4598-9-33. 20144215.