Activity of Tessaria absinthioides aqueous extract against MDA-MB-231 orthotopic tumors on NSG mice.

REAL S; HAPON MB; GAMARRA LUQUES C

Mendoza

Congreso; XXXIX Reunión Anual de la Sociedad de Biología de Cuyo.; 2021

Sociedad de Biología de Cuyo

The aqueous extract obtained from the leaves of Tessaria absinthioides (AETa) was reported as a cytotoxic and antitumoral botanical compound. Previous studies informed about the cytotoxicity against the human breast cancer cell line MDA-MB-231 (Basal: ER-, PR- and Her2- with p53mut) with an IC50 of 4.44 µg/mL after 48hs of treatment. In addition, when AETa was combined with paclitaxel (PTX, antimitotic), carboplatin (CBP, DNA damage) or doxorubicin (DXR, topoisomerase inhibitor) the cytotoxic activity resulted synergistic with calculated combination index values of 0.64, 0.57 and 0.87, respectively. Because these records, we hypothesize that AETa improve the antitumoral activity of PTX, CBP and DXR in vivo. Then, the goal of the current work was to evaluate in MDA-MB-231 xenograftorthotopic tumors the effects of AETa addition to the treatment with chemotherapic drugs. To start the study,2 tumors were induced in each NOD Scid Gamma mouse (NSG) by inoculation of 5 x 105 MDA-MB-231 cells into the 4th right and left mammary glands. When tumor´s volume reach 150 mm3, the animals were separated in 8 groups of 3 mice each (n=6 tumors). The treatments administrated were DXR (5 mg/kg, I.P.), PTX (5 mg/kg, I.P.) and CBP (30 mg/kg, I.P.) with or without AETa in the drinking water at 300 mg/kg/day (total 6 groups). Other 2 groups were added, one without any treatment (C0, control) and other treated only with AETa. The tumoral volume was measured twice a week and animals were euthanized when tumor reach 1 cm3 or when any signs of animal suffering appeared. The median survival was calculated by the Kaplan Maier analysis and groups were compared by the Mantel Cox test (significance p ≤ 0.05). Tumoral volume was compared the last day before any animal in the group was sacrifice by the Student T test (significance p ≤ 0.05) and it is expressed as median ± SEM. When the DXR and DXR-AETa groups are compared, the median survival is significantly increased in the DXR group (16 vs 11 days, after treatments started), and the tumor volume results significantly minor in the DXR-EATa mice (151.6 ± 16.9 vs 267.2 ± 19.4 mm3 at day 10th). All these animals were sacrificed because they showed evidence of treatment toxicity; in consequence, results confirm that AETa increases DXR toxicity both in tumors and in animals. In the other groups, there were not differences in the median survival (C0±AETa, 29 days; PTX±AETa, 29 days and CBP±AETa, 32 days). In relation to the tumor volume, at day 29th, no significant reduction was observed by administration of EATa alone compared with the C0 group. In the same day, the tumor volume in the PTX-AETa group resulted significantly smaller in comparison with group treated with PTX alone (784 ± 77.8 vs 1113 ± 101.4 mm3). Similarly, at day 32th, EATa addition to CBP treatment also increased a drug potency diminishing the final tumor volume from 1171 ± 52.5 to 1025 ± 111,8 mm3. In accordance to these preliminary results, it is possible to conclude that AETa collaborate to the chemotherapeutic drugs induced tumor reduction without causing changes in the animal median survival.