Abstract 4237: A natural product, NI-07, is effective in a wide variety of solid cancer cell types but exhibits no cytotoxic effects in normal cells

Abstract

Abstract Purpose: With the exception of a few anticancer agents, most chemotherapeutics currently used have devastating effects on normal cells. Here, we investigate the effectiveness of the natural product, NI-07, in a wide variety of cancer cell lines derived from solid tumors and normal cell types. Procedures: Cancer cells from breast, lung, prostate, pancreas, brain, bone, thyroid, cervical and colon, as well as normal foreskin and mammary fibroblasts and mammary epithelial cells were treated with 20X NI-07 in medium for 1 week. During the second week, cells were cultured untreated to analyze NI-07 effectiveness against resistance/recovery. In parallel, cells were untreated or treated with 2 × 10-6M Taxol for 24h, then replaced with untreated medium. Subsequently, breast cancer and normal epithelial cells were co-cultured and treated under the same conditions. In a separate experiment, normal cells were cultured in NI-07 and then treated with Taxol to observe whether NI-07 demonstrated a protective mechanism against Taxol insult. Cell viability was determined using cell counts, Trypan Blue exclusion and microscopy. Additionally, cell viability and NI-07 cytotoxicity were measured by XTT. The mechanism of cell death was analyzed using Annexin V. Three or more independent experiments were performed for each cell type. Statistical significance was determined using the Two-tailed Student's t tests at a p value < 0.05. Results: NI-07 had an attenuated effect on cancer cells. Significant declines in cell viability were observed after 4 days of treatment in contrast to the rapid affect of Taxol (∼24h). However, overall results demonstrated that the effect of NI-07 was comparable or superior to Taxol in killing cancer cells in all lines tested, with the exception of the colon cancer cells. Additionally, cancer cell recovery was less effective in NI-07 versus Taxol. Furthermore, NI-07 showed no cytotoxic effects to normal cells in parent cultures and preferentially affected cancer cells in co-culture. When cultured with NI-07, normal cells were measurably less affected by Taxol. Annexin V analysis showed that apoptosis was not the primary method of cell death by NI-07. We are currently investigating paraptosis as the mechanism of cell death. In vivo experiments using an athymic nude mouse model of injected human breast cancer cells is currently underway. Conclusions: NI-07, a novel natural product, effectively kills a wide variety of cancer cell types in vitro, while demonstrating no cytotoxic effects to normal cells. NI-07 preferentially affected cancer cells in co-culture and appeared to reduce the effects of Taxol on the normal cells. This lack of cytotoxicity and observed protective effects in normal cells, coupled with its killing efficiency in cancer cells, suggests that NI-07 could potentially make a strong anti-cancer agent or neo-adjuvant to current chemotherapy-based treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4237. doi:10.1158/1538-7445.AM2011-4237