A comprehensive review on anticancer mechanisms of the main carotenoid of saffron, crocin

Journal of Pharmacy and Pharmacology

Volumn 69, Issue 11, 2017, Pages 1419-1427

  Hoshyar, Reyhane ^a,b   Mollaei, Homa ^a,c  

^a BIRJAND UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^b BIRJAND UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c UNIVERSITY OF TABRIZ   (Iran)

Author keywords

anticancer; crocin; molecular mechanism; review

Indexed keywords

CROCIN; CYTOCHROME P450 2C9; DNA TOPOISOMERASE; LECTIN; STAT3 PROTEIN; TELOMERASE; ANTINEOPLASTIC AGENT; CAROTENOID; PLANT EXTRACT;

ANTINEOPLASTIC ACTIVITY; ANTIOXIDANT ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; CANCER INHIBITION; CELL DEATH; COMPUTER MODEL; CROCUS SATIVUS; DNA SYNTHESIS INHIBITION; DRUG MECHANISM; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME INHIBITION; EPIGENETICS; EPITHELIAL MESENCHYMAL TRANSITION; HUMAN; METASTASIS INHIBITION; MICROTUBULE; NONHUMAN; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; RNA SYNTHESIS; ANIMAL; CELL PROLIFERATION; CHEMISTRY; CROCUS; DRUG EFFECT; ISOLATION AND PURIFICATION; MOLECULARLY TARGETED THERAPY;

ANIMALS; ANTINEOPLASTIC AGENTS, PHYTOGENIC; APOPTOSIS; CAROTENOIDS; CELL PROLIFERATION; CROCUS; HUMANS; MOLECULAR TARGETED THERAPY; PLANT EXTRACTS;

EID: 85021809267     PISSN: 00223573     EISSN: 20427158     Source Type: Journal    
DOI: 10.1111/jphp.12776     Document Type: Review

References (78)

1. Hoshyar R et al. Anticancer effects of saffron stigma (Crocus Sativus): a review study. RJMS 2016; 22: 69–78.
2. Bolhassani A et al. Saffron and natural carotenoids: biochemical activities and anti-tumor effects. Biochim Biophys Acta 2014; 1845: 20–30.
3. Hoshyar R et al. Synergistic antitumor effects of crocin combined with hyperthermia on breast cancer cells. Breast 2015; 24: S71.
4. Hoshyar R et al. A novel green one-step synthesis of gold nanoparticles using crocin and their anti-cancer activities. J Photochem Photobiol 2016; 159: 237–242.
5. Bathaie SZ et al. Anticancer effects of crocetin in both human adenocarcinoma gastric cancer cells and rat model of gastric cancer. Biochem Cell Biol 2013; 91: 397–403.
6. Sarshoori JR et al. Neuroprotective effects of crocin on the histopathological alterations following brain ischemia-reperfusion injury in rat. Iran J Basic Med Sci 2014; 17: 895.
7. Mecocci P et al. Nutraceuticals in cognitive impairment and Alzheimer's. Front Pharmacol 2015; 88. https://doi.org/10.3389/fphar.2014.00147.
8. Li K et al. Crocin exerts anti-inflammatory and anti-catabolic effects on rat intervertebral discs by suppressing the activation of JNK. Int J Mol Med 2015; 36: 1291–1299.
9. Xiong Y et al. Anti-asthma potential of crocin and its effect on MAPK signaling pathway in a murine model of allergic airway disease. Immunopharmacol Immunotoxicol 2015; 37: 236–243.
10. Özdemir Ö. Any role for probiotics in the therapy or prevention of autoimmune diseases? Up-to-date review J Complement Integr Med 2013; 10: 229–250.
11. Kawabata K et al. Dietary crocin inhibits colitis and colitis-associated colorectal carcinogenesis in male ICR mice. Evid Based Complement Alternat Med 2012; Article ID 820415, 13 pages. https://doi.org/10.1155/2012/820415.
12. Adali F et al. Investigation of the effect of crocin pretreatment on renal injury induced by infrarenal aortic occlusion. J Surg Res 2016; 203: 145–153.
13. Wang Y et al. Experimental study of Saffron hepatotoxicity in rats. J Harbin Med Univ 2010; 2: 133–135.
14. Koutroubakis IE et al. Decreased total and corrected antioxidant capacity in patients with inflammatory bowel disease. Dig Dis Sci 2004; 49: 1433–1437.
15. Qi Y et al. Crocin prevents retinal ischaemia/reperfusion injury-induced apoptosis in retinal ganglion cells through the PI3K/AKT signalling pathway. Exp Eye Res 2013; 107: 44–51.
16. Deslauriers AM et al. Neuroinflammation and endoplasmic reticulum stress are coregulated by crocin to prevent demyelination and neurodegeneration. J Immunol 2011; 187: 4788–4799.
17. Bellezza I et al. Neuroinflammation and endoplasmic reticulum stress are coregulated by cyclo (His-Pro) to prevent LPS neurotoxicity. Int J Biochem Cell Biol 2014; 51: 159–169.
18. Kamalipour M et al. Cardiovascular effects of saffron: an evidence-based review. J Tehran Heart Cent 2011; 6: 59–61.
19. Bathaie SZ et al. Interaction of saffron carotenoids as anticancer compounds with ctDNA, Oligo (dG. dC) 15, and Oligo (dA. dT) 15. DNA Cell Biol 2007; 26: 533–540.
20. Hoshyar R et al. Interaction of safranal and picrocrocin with ctDNA and their preferential mechanisms of binding to GC-and AT-rich oligonucleotides. DNA Cell Biol 2008; 27: 665–673.
21. Shahi T et al. Main chemical compounds and pharmacological activities of stigmas and tepals of ‘red gold'; saffron. Trends Food Sci Technol 2016; 58: 69–78.
22. Bathaie SZ et al. A review of the chemistry and uses of crocins and crocetin, the carotenoid natural dyes in saffron, with particular emphasis on applications as colorants including their use as biological stains. Biotech Histochem 2014; 6: 401.
23. Naess et al. Hydrophilic carotenoids: surface properties and aggregation of crocin as a biosurfactant. Helv Chim Acta 2006; 89: 45–53.
24. Mohamadpour et al. Safety evaluation of crocin (a constituent of saffron) tablets in healthy volunteers. Iran J Basic Med Sci 2013; 16: 39–44.
25. Festuccia C et al. Antitumor effects of saffron-derived carotenoids in prostate cancer cell models. Biomed Res Int 2014, Article ID 135048, 12 pages. https://dx.doi.org/10.1155/2014/135048.
26. Chen Y et al. Comparative evaluation of the antioxidant capacity of crocetin and crocin in vivo. Chin Pharmacol Bull 2010; 26: 248–251.
27. Escribano J et al. Crocin, safranal and picrocrocin from saffron (Crocus sativus L.) inhibit the growth of human cancer cells in vitro. Cancer Lett 1996; 100: 23–30.
28. Hoshyar R et al. Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells. DNA Cell Biol 2013; 32: 50–57.
29. Ghadrdoost B et al. Protective effects of saffron extract and its active constituent crocin against oxidative stress and spatial learning and memory deficits induced by chronic stress in rats. Eur J Pharmacol 2011; 667: 222–229.
30. Farshid A et al. The effects of crocin, insulin and their co-administration on the heart function and pathology in streptozotocin-induced diabetic rats. Avicenna J Phytomed 2016; 6: 658–670.
31. Nam KN et al. Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells. Eur J Pharmacol 2010; 648: 110–116.
32. Zhang R et al. Comparison of the effects of crocetin and crocin on myocardial injury in rats. Chin J Nat Med 2009; 7: 223–227.
33. Beshbishy HA et al. Crocin “saffron” protects against beryllium chloride toxicity in rats through diminution of oxidative stress and enhancing gene expression of antioxidant enzymes. Ecotoxicol Environ Saf 2012; 83: 47–54.
34. Bisti S et al. Saffron and retina: neuroprotection and pharmacokinetics. Vis Neurosci 2014; 31: 355–361.
35. Bhandari P. Crocus sativus L. (saffron) for cancer chemoprevention: a mini review. J Tradit Complement Med 2015; 5: 81–87.
36. Abdullaev F et al. Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev 2004; 28: 426–432.
37. Ashrafi M et al. Effect of crocin on cell cycle regulators in N-nitroso-N-methylurea-induced breast cancer in rats. DNA Cell Biol 2015; 34: 684–691.
38. Bakshi H et al. DNA fragmentation and cell cycle arrest: a hallmark of apoptosis induced by crocin from kashmiri saffron in a human pancreatic cancer cell line. Asian Pac J Cancer Prev 2010; 11: 675–679.
39. Sun J et al. 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 2011; 12: 2679–2683.
40. AbdullaevF et al. Use of in vitro assays to assess the potential antigenotoxic and cytotoxic effects of saffron (Crocus sativus L.). Toxicol In Vitro 2003; 17: 731–736.
41. Lodish H et al. The Role of Topoisomerases in DNA Replication. Molecular Cell Biology. 4th edition. Section 12.3, 2000.
42. Bajbouj K et al. The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines. BMC Complement Altern Med 2012; 12: 69.
43. Hire RR et al. Antiproliferative activity of crocin involves targeting of microtubules in breast cancer cells. Sci Rep 2017; 7: 44984.
44. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007; 4: 495–516.
45. Amin A et al. Defective autophagosome formation in p53-null colorectal cancer reinforces crocin-induced apoptosis. Int J Mol Sci 2015; 16: 1544–1561.
46. Sun Y et al. Crocin exhibits antitumor effects on human leukemia HL-60 cells in vitro and in vivo. J Evid Based Complementary Altern Med 2013, Article ID 690164, 7 pages. https://dx.doi.org/10.1155/2013/690164.
47. Salem IB et al. Crocin, the main active saffron constituent, mitigates dichlorvos-induced oxidative stress and apoptosis in HCT-116 cells. Biomed Pharmacother 2016; 82: 65–71.
48. Kim B et al. Crocin suppresses constitutively active STAT3 through induction of protein tyrosine phosphatase SHP-1. J Cell Biochem 2017. https://doi.org/10.1002/jcb.25980.
49. Garc-Olmo DC et al. Effects of long-term treatment of colon adenocarcinoma with crocin, a carotenoid from saffron (Crocus sativus L.): an experimental study in the rat. Nutr Cancer 1999; 35: 120–126.
50. Shay JW et al. Defining the molecular mechanisms of human cell immortalization. Biochim Biophys Acta 1991; 1072: 1–7.
51. Kim NW et al. Specific association of human telomerase activity with immortal cells and cancer. Science 1994; 266: 2011–2015.
52. Noureini SK et al. Antiproliferative effects of crocin in HepG2 cells by telomerase inhibition and hTERT down-regulation. Asian Pac J Cancer Prev 2012; 13: 2305–2309.
53. Kalluri R et al. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119: 1420–1428.
54. Mancini A et al. Saffron extract and its major constituent crocin selectively inhibit the growth of human prostate cancer cell in vitro and in vivo. Eur J Cancer 2012; 48: S113.
55. Zheng Y-Q et al. Effects of crocin on reperfusion-induced oxidative/nitrative injury to cerebral microvessels after global cerebral ischemia. Brain Res 2007; 1138: 86–94.
56. Soszyński M et al. Decrease in accessible thiols as an index of oxidative damage to membrane proteins. Free Radic Biol Med 1997; 23: 463–469.
57. Daly E. Protective effect of cysteine and vitamin E, Crocus sativus and Nigella sativa extracts on cisplatin-induced toxicity in rats. J Pharm Belg 1997; 53: 87–93.
58. Mostafavinia SE et al. Antiproliferative and proapoptotic effects of crocin combined with hyperthermia on human breast cancer cells. DNA Cell Biol 2016; 35: 340–347.
59. Boussabbeh M et al. Crocin protects the liver and kidney from patulin-induced apoptosis in vivo. Environ Sci Pollut Res 2016; 10: 9799–9808.
60. Grønbæk K et al. Epigenetic changes in cancer. Apmis 2007; 115: 1039–1059.
61. Hoshyar R et al. Is there any interaction between telomeric DNA structures, G-quadruplex and I-motif, with saffron active metabolites? Nucleosides, Nucleotides Nucleic Acids 2012; 31: 801–812.
62. Ashrafi M et al. The effect of carotenoids obtained from saffron on histone H1 structure and H1–DNA interaction. Int J Biol Macromol 2005; 36: 246–252.
63. Hoshyar R et al. The impact of active metabolites obtained from saffron on H1–Oligonucleotide interaction. J Biomol Struct Dyn 2013; 31 (Suppl. 1): 62.
64. Ganaie MA et al. Phytochemical screening and in-silico investigation of crocin and safranal, constituents of saffron for their cytochrome P450 2C9 enzyme activity. Int J Pharm Res Allied Sci 2017; 1: 1–14.
65. Aung H et al. Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol 2007; 29: 175.
66. D'Alessandro AM et al. Crocus sativus stigma extract and its major constituent crocin possess significant antiproliferative properties against human prostate cancer. Nutr Cancer 2013; 65: 930–942.
67. Tarantilis P et al. Inhibition of growth and induction of differentiation of promyelocytic leukemia (HL-60) by carotenoids from Crocus sativus L. Anticancer Res 1993; 14: 1913–1918.
68. Morjani H et al. Growth inhibition and induction of crythroid differentiation activity by crocin, dimethylcrocetine and b-carotene on K562 tumor cells. Anticancer Res 1990; 10: 1398–1406.
69. Zhang Z et al. Role of saffron and its constituents on cancer chemoprevention. Pharm Biol 2013; 51: 920–924.
70. Chryssanthi DG et al. Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. Anticancer Res 2007; 27: 357–362.
71. Fanayi AR et al. Effect of crocin and doxorubicin/radiation on the breast cancer cell line, Michigan Cancer Foundation-7. Bioscience biotechnology research communications 2016; 9: 428–434.
72. Mahdizadeh S et al. Crocin suppresses multidrug resistance in MRP overexpressing ovarian cancer cell line. Daru 2016; 24: 17.
73. Mousavi SH et al. Study of crocin & radiotherapy-induced cytotoxicity and apoptosis in the head and neck cancer (HN-5) cell line. Iran J Pharm Res 2017; 16: 230–237.
74. Chen S et al. Crocin inhibits cell proliferation and enhances cisplatin and pemetrexed chemosensitivity in lung cancer cells. Transl Lung Cancer Res 2015; 4: 775.
75. Rezaee R et al. Crocin effects on human myeloma cells regarding intracellular redox state, DNA fragmentation, and apoptosis or necrosis profile. Jundishapur J Nat Pharm Prod 2014; 9: e20131.
76. Zhao P et al. Proliferation apoptotic influence of crocin on human bladder cancer T24 cell line. China J Chin Mater Med 2008; 33: 1869–1873.
77. Li X et al. Synergistic apoptotic effect of crocin and cisplatin on osteosarcoma cells via caspase induced apoptosis. Toxicol Lett 2013; 221: 197–204.
78. Vali F et al. Synergistic apoptotic effect of crocin and paclitaxel or crocin and radiation on MCF-7 cells, a type of breast cancer cell line. Int J Breast Cancer 2015, Article ID 139349, 7 pages. http://dx.doi.org/10.1155/2015/139349.