Cell lines

p53 wild-type or p53-deficient human colon cancer HCT-116 cell lines

Preparation method

The solubility of this compound in DMSO is > 10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0-1000 μM; 24 h (cell cycle distribution) or 72 h (apoptosis).

Applications

In a colony forming assay, S-ibuprofen and R-ibuprofen exhibited significantly higher anti-proliferative effects in the p53wt cell line than in the p53-deficient HCT-116 cells. In HCT-116 p53wt cells, 800-1000 μM S-ibuprofen and R-ibuprofen reduced cells in the S and G2/M phases and significantly increased the number of cells in the G0/G1-phase. 800-1000 μM S- and R-ibuprofen also significantly increased apoptosis.

Animal models

Athymic nude mice xenografted with implanted subcutaneously with HCT-116 p53wt and p53-/- colon cancer cells

Dosage form

five days a week intraperitoneally with 15 mg/kg/day, suspended in PBS (pH 7), 5 weeks

Application

Compared with the tumour volumes of untreated mice, R-ibuprofen significantly reduced the growth of p53wt expressing xenografts. S-ibuprofen also reduced the growth of p53wt expressing xenografts. But only a small and non-significant inhibition of HCT-116 p53-/- tumour growth after S- or R-ibuprofen treatment.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Ibuprofen is an inhibitor of cyclooxygenase 1 and cyclooxygenase 2 with IC50 values of 12 and 80 μM, respectively [1].

Cyclooxygenase (COX) is an enzyme that is responsible for the formation of prostaglandins, prostacyclin and thromboxane.

In HCT-116 p53wt or HCT-116 p53-/-colon carcinoma cell lines, S- and R-ibuprofen induced apoptosis and blocked cell cycle is in part dependent on p53. The anti-proliferative effects were significantly higher in the p53wt cell line than in the p53-deficient cells [2].

In nude mice model bearing HCT-116 p53wt and p53-/- xenografts, R-ibuprofen significantly inhibited the growth of p53wt expressing xenografts and only a small inhibition of p53-/- xenografts [2]. In hypercholesterolemic animals, ibuprofen reduced the levels of total cholesterol, VLDL, LDL, triglycerides and atherogenic index. Also, ibuprofen inhibited COX enzymes and inhibited the generation of free radicals during prostaglandins synthesis, which reduced the levels of lipid peroxidation, superoxide dismutase [3]. In rats, ibuprofen (60 mg/kg) improved mechanical hyperalgesia through reducing central hyperexcitability [4].

References:
[1].  Kato M, Nishida S, Kitasato H, et al. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes. J Pharm Pharmacol, 2001, 53(12): 1679-1685.
[2].  Janssen A, Schiffmann S, Birod K, et al. p53 is important for the anti-proliferative effect of ibuprofen in colon carcinoma cells. Biochem Biophys Res Commun, 2008, 365(4): 698-703.
[3].  Dabhi JK, Solanki JK, Mehta A. Antiatherosclerotic activity of ibuprofen, a non-selective COX inhibitor--an animal study. Indian J Exp Biol, 2008, 46(6): 476-481.
[4].  Redondo-Castro E, Navarro X. Chronic ibuprofen administration reduces neuropathic pain but does not exert neuroprotection after spinal cord injury in adult rats. Exp Neurol, 2014, 252: 95-103.