Abstract

Abstract Research studies have demonstrated that breast cancers display different chemosensitivity parameters depending on the nature of the genetic lesions. Breast cancers with BRCA-1 mutations respond better to DNA inhibitors such as cisplatin, than to agents that interfere with microtubule function, such as Taxol. Moreover, breast cancers that are estrogen and/or progesterone (ER/PR) negative generally display poorer responses to standard chemotherapy than ER/PR receptor positive breast cancers. This research study was designed to test the potential cytotoxic activity of phytochemical extracts prepared from fern species native to New England on a variety of breast cancer cell lines with diverse genetic properties. Since primitive plant species contain many phytochemicals with chemoprotective as well as immunoprotective properties, our research hypothesis involved the concept that these chemicals might also display anti-cancer properties as previously observed for plant alkaloids such as vincristine, vinblastine and paclitaxel. Fresh plant specimens were washed, dried and then extracted in 70% boiling methanol. The plant material was then homogenized and centrifuged. The supernatant was collected, the solvent was evaporated and the solute component was resuspended in aqueous solution to effect a 1000X concentration. The extract preparation was stored at 4C and appeared to be stable for at least six months. Further extraction in chloroform was performed on the alcoholic extracts, which produced three layers: a polar/aqueous layer, a nonpolar layer and an amphipathic, lipid-like layer. Each layer was assessed for cytotoxicity and then subjected to the same phytochemical screening as the original, whole extract, which showed the presence of complex phenolics and terpenoids. This concentrated phytochemical extract was tested for activity in diverse human cancer at varying dose ranges. The cell lines assessed in this study included MCF-7, which is a ductal breast carcinoma that is ER/PR positive; HTB-126 which is ER/PR negative and its normal cell counterpart, HTB-125; and HCC 1937 which contains a mutation in the BRCA-1 gene. Our preliminary results indicate that the fern phytochemical extract has a higher efficacy targeting the malignant cells when compared to standard chemotherapeutics currently used in patients. The effective dose range was between 5-15 mcg/mL in 48 hours treatment. This level of activity was comparable and even higher than that observed for the standard chemotherapeutic agents tested. In addition, extract concentration between 5-10mcg/mL produced little cytotoxicity in normal breast cells; some cytotoxic effects were observed at higher doses. Additional studies will attempt to characterize more fully the phytochemical components most active in eliciting these anti-tumor effects. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 776.

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