Screening of synergistic combinations between Tessaria absinthioides aqueous extract and current chemotherapeutics on MCF-7 cell line.

TRONCOSO M.; GAMARRA LUQUES, C; RINALDINI, E; PERSIA, FA; HAPON, MB

Mendoza

Congreso; XXXVI Reunión ciéntifica anual de la Sociedad de Biología de Cuyo.; 2018

Sociedad de Biología de Cuyo

Tessaria absinthioides (HOOK & ARN) DC is a native plant from Mendoza ? Argentina with reported ethno, pharmacologyl and culinary uses. By the use of the aqueous extract (TaAE), previous studies performed in our laboratory demonstrate its cytotoxic activity against several human cancer cell lines. The cytotoxicity was significantly reduced when non-tumoral cells were assayed. In laboratory animals, acute, sub-chronic and reproductive toxicities were discarded at doses up 300 mg/animal/day when orally administrated. The antitumoral effects of the TaAE were evidenced in two different models of allograft mice tumors. At the mentioned doses, when is orally administrated, the TaAE significantly increases the median survival of animals with colorectal cancer and significantly reduces the weight and volume of subcutaneous melanomas. To promote the TaAE use as a complementary agent to cancer treatment, the goal of the present work was to study the capability of TaAE to synergize current commercially available chemotherapeutics. The cytotoxicity of the TaAE, carboplatin (Cbp), ciclofosfamide, doxorubicin (Dxr), metrotrexate, paclitaxel (Ptx), tamoxifen (Tmx) and 5-fluoracile were determined by the MTT assay. Then, concentrations lower than the CC50 (concentration where the 50% of cytotoxicity is reached) were used in combination with a fixed dose of TaAE (CC25 = 3.75μg/ml). The Calcusyn® software calculated combination index (CI) and values lower than one were considered as a synergistic combination. Between the seven chemotherapeutic agents assayed, TaAE acts synergistically with four of them: the DNA damage agent Cbp, the topoisomerase inhibitor Dxr, the selective estrogen receptor modulator Tmx and the antimitotic Ptx. The best CI obtained in each case were Cbp = 0.79 (7.5μg/ml + TaAE); Dxr = 0.59 (32ng/ml + TaAE); Tmx = 0.73 (6.25μg/ml + TaAE); and Ptx = 0.70 (0.6μg/ml + TaAE). Together, these chemotherapies represent the elective treatment for several types of cancer, such as breast, colorectal, lung, stomach, bladder, leukemia, ovary, head and neck, sarcoma, neuroblastoma and thyroid cancer. In our country, in accordance to the Globocam statistics (2012), seven of them are reported between the cancers with higher incidences. In conclusion, the presented results open a new perspective about the use of TaAE as complementary treatment in current available cancer approaches. Future research need to specify the cytotoxic mechanisms involved, its molecular intermediaries and its activity confirmation by the use of in vivo models.