The Natural Product NI-07, Is Effective Against Breast Cancer Cells While Showing No Cytotoxicity to Normal Cells

Abstract

Abstract:With the exception of a few anticancer agents, most breast cancer chemotherapeutics currently used have devastating effects on normal cells. We investigated the effectiveness of the natural product NI-07, derived from Arctium lappa, to determine its killing potential on breast cancer cells and its cytotoxic effects in breast normal cells. The breast cancer cell lines HCC1419, MCF7, MDA-MB-231, MDA-MB-468, SKBR3, the normal mammary epithelial cell line HME 50 HT and the normal mammary fibroblast cell line CCD-1074sk were analyzed in concurrently treated cultures of NI-07, Taxol™ or Untreated. NI-07-treated and Taxol™ -treated cells were cultured for two weeks to assess cell resistance/recovery. Cell viability was determined by cell counts, Trypan Blue exclusion and microscopy. Additionally, cell viability and cytotoxicity were measured by XTT. Statistical significance (p 0.05) of NI-07 to Untreated or Taxol™ was first determined using Two-Way ANOVA. Identified significant differences were further analyzed by One-Way ANOVA and Tukey's test for honestly significant differences. The effect size of NI-07 compared to untreated or Taxol™ was determined using Cohen's d. Our results showed significant declines in cell viability occurring in NI-07-treated cancer cells after 48 hours of treatment in contrast to the more rapid effect of Taxol™ (<24h). Additionally, cancer cell recovery was less effective in NI-07 versus Taxol™. Furthermore, NI-07 showed no cytotoxicity in normal cells. This lack of cytotoxicity, coupled with its killing efficiency in cancer cells, suggests that NI-07 could potentially make a strong anti-cancer compound or neo-adjuvant to current chemotherapy-based treatments.

The natural product NI-07 demonstrates effective anti-cancer properties against numerous cancer cell types

“…This swelling and vacuolization has been shown to be involved with disruption of intracellular ion homeostasis resulting in a heat shock proteins response [43] , among other inducers [44] . This speculation is based on the morphological changes observed in this study and our prior study [15] as well as our unpublished XTT assay results. Studies show that XTT dye reduction occurs at the cell surface facilitated by trans-plasma membrane electron transport of which, mitochondrial oxidoreductases are major contributors [45] .…”

“…This 100% water-soluble compound is a mixture of several molecules implicated as having potential anticancer effects along with the novel reactive NI species. These compounds included 2-methyl-butyric acid, alanine, chlorogenic acid, sinigrin, and valine in addition to the active NI ingredient, which was confirmed to be 191.2 g/mol, existing in a dihydrate form, C 8 H 13 NO 2 •2H 2 O [23] . The focus of that study was to determine the effectiveness of NI-07 on breast cancer cells and the potential cytotoxic effects to normal cells.…”

“…Although NI-07 did not cause total remission of the cancer, there was a significant reduction in tumor burden and growth over the test period (p ≤ 0.004). Our previous study demonstrated that NI-07 has no cytotoxic effects to normal cells [23] and the mice treated with NI-07 were the most vigorous of the three treatments groups. Thus the possibility exists that NI-07 could be administered either at higher concentrations or for longer treatment periods or both with little side effects or reduction in the quality of life for the patient.…”

“…Titration experiments (data not shown) determined this to be the approximate lowest lethal concentration to kill ~50% of the cells (LC50) over the treatment period of 7 days. NI-07 test cells were continuously exposed for 7 days [23] . Medium alone (Taxol™ and Untreated) or Medium with NI-07 was refreshed on day 3.…”

“…In our previous study, the physical and chemical characteristics of the natural product compound NeoImmune®-07 (NI-07) were described [15] . This 100% water-soluble compound is a mixture of several molecules implicated as having potential anticancer effects along with the novel reactive NI-07 species.…”