- Volume 13 Issue 8
DOI QR Code
Crocetin Induces Cytotoxicity in Colon Cancer Cells Via p53-independent Mechanisms
- Li, Cai-Yan ;
- Huang, Wen-Feng ;
- Wang, Qun-Li ;
- Wang, Fan ;
- Cai, E. ;
- Hu, Bing ;
- Du, Jia-Cheng ;
- Wang, Jing ;
- Chen, Rong ;
- Cai, Xiao-Jing ;
- Feng, Jing ;
- Li, Hui-Hui
- Published : 2012.08.31
Objective: Crocin has been proposed as a promising candidate for cancer chemoprevention. The purpose of this investigation was to investigate the chemopreventive action and the possible mechanisms of crocin against human colon cancer cells in vitro. Methods: Cell proliferation was examined using MTT assay and the cell cycle distribution fractions were analyzed using fow cytometric analysis after propidium iodide staining. Apoptosis was detected using theTUNEL Apoptosis Detection Kit with laser scanning confocal microscope. DNA damage was assessed using the alkaline single-cell gel electrophoresis assay, while expression levels of p53, cdk2, cyclinA and P21 were examined by Western blot analysis. Results: Treatment of SW480 cells with crocetin (0.2, 0.4, 0.8 mmol/L) for 48 h signifcantly inhibited their proliferation in a concentration-dependent manner. Crocetin (0.8 mmol/L) signifcantly induced cell cycle arrest through p53-independent mechanisms accompanied by P21 induction. Crocetin (0.8 mmol/L) caused cytotoxicity in the SW480 cells by enhancing apoptosis and decreasing DNA repair capacity in a time-dependent manner. Conclusions: This report provides evidence that crocetin is a potential anticancer agent, which may be used as a chemotherapeutic drug.
Crocetin;cell cycle;apoptosis;DNA damage;p21;neoplasm
- Abdullaev F (2002). Cancer chemopreventive and tumoricidal properties of saffron (Crocus sativus L.). Exp Biol Med, 227, 20-5. https://doi.org/10.1177/153537020222700104
- Abdullaev F, Espinosa J (2004). Biomedical properties of saffron and its potential use in cancer therapy and chemoprevention trials. Cancer Detect Prev, 28, 426-32. https://doi.org/10.1016/j.cdp.2004.09.002
- Abdullaev F, Rivera R, Roitenburd V, et al (2000). Pattern of childhood cancer mortality in Mexico. Arch Med Res, 31, 526-31. https://doi.org/10.1016/S0188-4409(00)00094-1
- Ahmad AS, Ansari MA, Ahmad M (2005). Neuroprotection by crocetin in a hemi-parkinsonian rat model. Pharmacol Biochem Behav, 81, 805-13. https://doi.org/10.1016/j.pbb.2005.06.007
- Aizat AAA, Shahpudin SNM, Mustapha MA, et al (2011). Association of Arg72Pro of P53 polymorphism with colorectal cancer susceptibility risk in Malaysian population. Asian Pac J Cancer Prev, 12, 2909-13.
- Amin A, Hamza AA, Bajbouj K, et al (2011). Saffron: a potential candidate for a novel anticancer drug against hepatocellular carcinoma. Hepatology, 54, 857-67. https://doi.org/10.1002/hep.24433
- Aung HH, Wang CZ, Ni M (2007). Crocin from Crocus sativus possesses significant anti-proliferation effects on human colorectal cancer cells. Exp Oncol, 29, 175-80.
- Bajbouj K, Schulze LJ, Diermeier S (2012). The anticancer effect of saffron in two p53 isogenic colorectal cancer cell lines. BMC Complement Altern Med, 12, 69. https://doi.org/10.1186/1472-6882-12-69
- Cai J, Yi FF, Bian ZY (2009). Crocetin protects against cardiac hypertrophy by blocking MEK-ERK1/2 signalling pathway. J Cell Mol Med, 13, 909-25. https://doi.org/10.1111/j.1582-4934.2008.00620.x
- Chryssanthi DG, Lamari FN, Iatrou G (2007). Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. Anticancer Res, 27, 357-62.
- Das I, Das S, Saha T: Saffron suppresses oxidative stress in DMBA-induced skin carcinoma: A histopathological study. Acta Histochem, 112, 317-27.
- Dhar A, Cherian G, Dhar G (2005). Molecular basis of protective effect by crocetin on survival and liver tissue damage following hemorrhagic shock. Mol Cell Biochem, 278, 139-46. https://doi.org/10.1007/s11010-005-7155-1
- Dhar A, Mehta S, Dhar G (2009). Crocetin inhibits pancreatic cancer cell proliferation and tumor progression in a xenograft mouse model. Mol Cancer Ther, 8, 315-23. https://doi.org/10.1158/1535-7163.MCT-08-0762
- Elledge SJ (1996). Cell cycle checkpoints: preventing an identity crisis. Science, 274, 1664-72. https://doi.org/10.1126/science.274.5293.1664
- Harrison S, Benziger H (2011). The molecular biology of colorectal carcinoma and its implications: A review. Surgeon, 9, 200-10. https://doi.org/10.1016/j.surge.2011.01.011
- Heah KG , Hassan MI, Huat SC (2011). p53 Expression as a marker of microinvasion in oral squamous cell carcinoma. Asian Pac J Cancer Prev, 12, 1017-22.
- He SY, Qian ZY, Wen N (2007). Infuence of Crocetin on experimental atherosclerosis in hyperlipidamic-diet quails. Eur J Pharmacol, 554, 191-5. https://doi.org/10.1016/j.ejphar.2006.09.071
- Jagadeeswaran R, Thirunavukkarasu C, Gunasekaran P (2000). In vitro studies on the selective cytotoxic effect of crocetin and quercetin. Fitoterapia, 71, 395-99. https://doi.org/10.1016/S0367-326X(00)00138-6
- Kanakis C, Tarantilis P, Pappas C (2009). An overview of structural features of DNA and RNA complexes with saffron compounds: Models and antioxidant activity. J Photochem Photobiol B, 95, 204-12. https://doi.org/10.1016/j.jphotobiol.2009.03.006
- Lee I, Lee J, Baek N (2005). Antihyperlipidemic effect of crocin isolated from the fructus of Gardenia jasminoides and its metabolite Crocetin. Biol Pharm Bull, 28, 2106-10. https://doi.org/10.1248/bpb.28.2106
- Lee SJ, Ha MJ, Lee J (1998). Inhibition of the 3-hydroxy-3- methylglutaryl-coenzyme A reductase pathway induces p53-independent transcriptional regulation of p21WAF1/ CIP1 in human prostate carcinoma cells. J Biol Chem, 273, 10618-23. https://doi.org/10.1074/jbc.273.17.10618
- Liu RH (2004). Potential synergy of phytochemicals in cancer prevention: Mechanism of action. J Nutr, 134, S3479-85. https://doi.org/10.1093/jn/134.12.3479S
- Mousavi SH, Tavakkol AJ, Brook A (2009). Role of caspases and Bax protein in saffron-induced apoptosis in MCF-7 cells. Fd Chem Toxicol, 47, 1909-13. https://doi.org/10.1016/j.fct.2009.05.017
- Nakano K, Mizuno T, Sowa Y (1997). Butyrate activates the WAF1/Cip1 gene promoter through Sp1 sites in a p53- negative human colon cancer cell line. J Biol Chem, 272, 22199-206. https://doi.org/10.1074/jbc.272.35.22199
- Ordoudi S, Befani C, Nenadis N (2009). Further examination of antiradical properties of Crocus sativus stigmas extract rich in crocins.J Agric Food Chem, 57, 3080-6. https://doi.org/10.1021/jf804041g
- Tavakkol AJ, Brook A, Mousavi SH (2008). Study of cytotoxic and apoptogenic properties of saffron extract in human cancer cell lines. Fd Chem Toxicol, 46, 3443-7. https://doi.org/10.1016/j.fct.2008.08.018
- Yanatatsaneeji P, Kitkumthorn N, Dhammawipark C, er al (2010). Codon72 polymorphism in the p53 tumor suppressor gene in oral lichen planus lesions in a Thai population. Asian Pac J Cancer Prev, 11, 1137-41.
- Zheng S, Qian Z, Tang F (2005). Suppression of vascular cell adhesion molecule-1 expression by crocetin contributes to attenuation of atherosclerosis in hypercholesterolemic rabbits. Biochem Pharmacol, 70, 1192-9. https://doi.org/10.1016/j.bcp.2005.07.034
- Zhong YJ, Shi F, Zheng XL (2011). Crocetin induces cytotoxicity and enhances vincristine-induced cancer cell death via p53- dependent and -independent mechanisms. Acta Pharmacol Sin, 32, 1529-36. https://doi.org/10.1038/aps.2011.109
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