Phytochemical characterization and assessment of antitumor activity of the aqueous extract of Acmella caulirhiza in female Wistar rats induced by 7,12 dimethylbenz (a) anthracene

Abstract

Recent studies increasingly show the implication of medicinal plants in cancer management. Acmella caulirhiza, a plant belonging to the Asteraceae is traditionally used as an analgesic and anti-inflammatory agent to fight against diseases like cancer. Purpose: This study aimed to evaluate the antitumoral properties of the aqueous extract of leaves and flowers of Acmella caulirhiza (AE-Ac). After phytochemical characterization, the cytotoxic activity of AE-Ac on MCF-7 breast cancer lines was carried out using the MTT method. For in vivo study, 36 female Wistar rats (6 weeks old) were randomly divided into 6 groups (n=6 each) as follows: normal control receiving distilled water (NC), positive control receiving distilled water (DMBA), 3 test groups (receiving either 75, 150 or 300 mg/kg.Bw of AE-Ac (AE-Ac 75, AE-Ac 150 and AE-Ac 300 respectively)) and a reference group (Tam) receiving Tamoxifen at 3.3 mg/kg.Bw. They were fed with a high-fat diet daily. After 2 weeks all groups except the NC group were treated with a single dose of DMBA (7,12-Dimethylbenz (a) anthracene) (50 mg/kg. Bw) by intraperitoneal injection. Daily treatments were administered by intragastric intubation for 12 weeks. At the end, animals were sacrificed after 12 hours of fasting and blood was collected for biochemical analysis. The mammary glands were isolated for histological analysis. Results. AE-Ac contains bioactive compounds amongst which stigmasterol, phytol, ellagic acid, phenol, sterols, alkaloids, flavonoids. AE-Ac was more active at 72h (IC50 = 114.86 µg/mL) on MCF-7 cells. The cancer-treated groups exhibited the lowest percentage of weight gain variation, particularly the group receiving the reference molecule (Tamoxifen) (68.12 %) followed by the AE-Ac 150 group (92.45 %). AE-Ac at 150 and 300 mg/kg-Bw significantly reduced tumor volume and CA 15-3 levels (p=0.004). Histological analysis of the mammary gland revealed more extensive ascini destruction in the AE-Ac 75 group followed by the DMBA group. Treatment with the 150 mg/kg.Bw ameliorated antioxidant enzyme (SOD and Catalase (p<0.001)) activities, pro-oxidant levels (NO● and HO●), as well as inflammatory parameters (TNF-α and EGF; RBC, Hb, PLT) (p<0.05). Conclusion. These results suggest that AE-Ac can be a good candidate as a complementary agent in breast cancer management.