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

Abstract

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.

Chlorogenic Acid and Cinnamaldehyde in Combination Inhibit Metastatic Traits and Induce Apoptosis via Akt Downregulation in Breast Cancer Cells

“…However, when these natural compounds enter the cytosol, they may act as either competitive inhibitors, binding to the Akt active site and thereby blocking ATP binding and its consequent activation [42] or behave as allosteric inhibitors by binding to the PH domain of the protein, thereby altering the Akt tertiary structure, which affects its function and makes Akt binding to other proteins impossible [42]. While the exact mechanism(s) of action of CGA-CA's inhibition of Akt activation may not be known, our previous work [18,20,21], taken together with this study, suggests that phytochemicals affect multiple molecular targets in the cells to bring about their biological effects. One of these mechanisms involves the downregulation of Akt activation.…”

“…Combinations of different phytochemicals for treatments of cancer cells have been shown to produce a stronger biological impact than the individual components [ 17 , 18 , 19 ]. In our prior studies [ 18 , 20 , 21 ], it was shown that plant extracts within a mixture killed cancer cells with little or no cytotoxicity to normal cells. Thus, the idea was not to specifically target metastatic cancer cells but to exploit the co-evolutionary relationship of humans with natural products to “shower the cells” with phytochemicals.…”

Natural Compounds and Breast Cancer: Chemo-Preventive and Therapeutic Capabilities of Chlorogenic Acid and Cinnamaldehyde

“…While other methods have shown simultaneous promise and challenges, the use of plant-derived natural compounds has been proven to hold the much-sought-after Ehrlich’s “poison arrow”. This is because of their unmatched effectiveness in their cytotoxic effects against breast cancer cells and other types of neoplastic diseases, their bioavailability, and safety to normal cells as well as their capability to prevent cancer relapse [ 4 , 5 , 7 , 8 , 9 , 10 , 42 , 43 , 44 ].…”

“…Moreover, research into natural compounds as an alternative method in cancer treatment has received overwhelming interest owing to their relative safety and ability to affect multiple molecular targets in cancer cells. Phytochemical agents have been reported to show effectiveness against different types of cancer including various types of breast cancer through varied mechanistic processes such as the induction of apoptosis, the inhibition of DNA replication, the inhibition of telomerase, the dysregulation of mitotic cell division, angiogenic and metastatic process inhibition, and the induction of differentiation in cancer cells [ 6 , 7 , 8 , 9 , 10 , 11 ].…”

“…Well-known examples of plantbased natural products, which are also called phytochemicals, are curcumin, carotenoids, genistein, daidzein, resveratrol, ellagic acid, punicalagin, and silibinin [4]. Phytochemical Pharmaceuticals 2024, 17, 361 2 of 24 agents have displayed anti-inflammatory, anti-proliferative, anti-metastatic, antiviral, proapoptotic, and free radical scavenging capacities in vitro and in vivo [6][7][8][9]. Moreover, research into natural compounds as an alternative method in cancer treatment has received overwhelming interest owing to their relative safety and ability to affect multiple molecular targets in cancer cells.…”