Background: With the exception of a few anticancer agents, most chemotherapeutics currently used have varying effects on cancer cells and devastating effects on normal cells. Previously, we showed the natural product compound NI-07 was effective against breast cancer cells. Here, we investigated its effectiveness in vitro on six different cancer types. Additionally, NI-07 was tested in vivo by injecting human melanoma cells WM-266-4 into BALB/c mice and treating with NI-07, cisplatin or untreated. Methods: For in vitro experiments, human cancer cell lines H1299, PC-3, AsPc-1, TT, Saos-2, and the rat C6 glioma cell line were analyzed in concurrently treated cultures of NI-07 (36.6 mM), Taxol™ (2 × 10-6M Taxol for 24h) or untreated for 1 week. In week 2, cells were analyzed for NI-07 effectiveness against resistance/recovery. Cell death was determined by cell counts, Trypan Blue exclusion and microscopy. Cell viability and cytotoxicity were measured by XTT. Three or more independent experiments were performed for each cell type. For in vivo experiments, 105 WM-266-4 melanoma cells were injected into the right flank of 5-week-old female nude mice (BALB/c nu/nu) and treated by gavage with 0.0035mg/g NI-07. Untreated or Cisplatin (0.0025mg/g) treated mice were used as control groups. Statistical significance was determined using One-way ANOVA, Tukey's HSD (p ≤ 0.05) and Cohens d (p ≤ 2.0).
Results:In vitro results for NI-07 showed significant declines in cell viability between 48h -4d of treatment. Overall results demonstrated that the effect of NI-07 was comparable or superior to Taxol in killing cancer cells in all lines tested. Cancer cell recovery was less effective in NI-07 versus Taxol. In vivo results showed that NI-07 significantly slowed the tumor growth in comparison to untreated and cisplatin-treated mice.Conclusions: NI-07, a novel natural product, effectively kills a wide variety of cancer cell types in vitro. Additionally, results showed that NI-07 was significantly more effective at slowing/reducing melanoma growth in a mouse model, in comparison to controls. Statistical significance (p ≤ 0.05) of NI-07 to Untreated, Taxol™ or cisplatin was determined using One-Way ANOVA and Tukey's HSD test.
