Effets anticancéreux et chimioprotecteur de l’extrait polyphénolique, riche en flavonoïdes, des feuilles de Cléome arabica

Abstract

Cleome arabica L. (Capparaceae) is a medicinal and a desert plant widely distributed in the north part of Africa and it’s used for the treatment of abdominal and rheumatic pains. In the present study, the polyphenolic extract from Cleome arabica leaves (CALE) was investigated for: (i) The antioxidant activity in vitro using DPPH., metal chelating and reducing power methods. (ii) The anticancer effects using five different human cancer cell lines, MCF-7, DLD-1, HepG2, HeLa and SK-N-BE, by evaluating cell viability and measurement of cell cycle distribution using hemocytometer chamber and a cytofluorimeter, respectively. The EGF was used as a positive control. A western blot was performed to evaluate the CALE effects on pathways involved in cell growth regulation and on apoptotic cascade activation. (iii) The protective effects against AraC induced hematological toxicity in mice by establishing the complete blood count test and by measurement of mice body temperature. The obtained results indicated that CALE exhibited a strong scavenging activity against DPPH. free radical (IC50 = 4.88 µg/ml) and a high reducing power, while, the chelating activity was good only at high concentrations (IC50 = 377,75 µg/ml). Furthermore, the obtained results showed that the subcutaneous injection of 50 mg/kg of AraC to mice during three consecutive days caused a significant myelosupression. Indeed, the number of the red and white blood cells, the amount of hemoglobin and the percentage of the hematocrit decreased significantly (p<0,001). However, the intraperitoneal injection of the extract (100 mg/kg) during six consecutive days didn’t exert any toxicological effects. The combination of CALE and AraC protected blood cells from a veritable toxicity. In fact, the number of the red cells, the amount of hemoglobin and the percentage of the hematocrit were significantly high. However, the number of the white blood cells was slightly protected. In addition, CALE exerted an antipyretic activity by maintaining mice body temperature a round 37°C in the group treated with the combination of CALE and AraC, against 39°C in the group treated with AraC alone. Moreover, the obtained results showed that the treatment of the five cancer cell lines with CALE at different concentrations (1, 5, 10, 25, 50, 100 and 200 µg/ml) reduced cell number in a dose dependent manner. Thus, the apoptotic cascade involving caspase-3 activation and the cleavage of its substrate PARP was increased by three-fold using CALE at 100 and 200 µg/ml. Interestingly, CALE treatment (200 µg/ml) also blocked EGF-induced cell growth by preventing the growth factor-triggered AKT and ERK phosphorylation and Bcl-2 levels. As a whole, these data strongly suggest that CALE possesses anticancer effects on all tested cancer cell lines. As a conclusion, the biological activities of CALE, observed in vitro as well as in vivo, could be due to its richness in polyphenols and flavonoïds which represent 322.1 ± 3.44 mg equivalent of gallic acid/g of extract and 245.6 ± 4.67 mg equivalent of quercetin/g of extract, respectively.