RESUMO
Background: Annonaceous acetogenins have been reported to have anti-cancer properties but low viability. In this study, we aimed to investigate the potency of nanodiamonds to be employed as a carrier of annonacin to help increase its viability and inhibit the growth of breast cancer cells. Methods: The annonacin was coupled with nanodiamond and characterized using UV-Vis spectrophotometer, FTIR, SEM, and PSA, and determined their stability and drug release. A cell growth inhibition assay and cell migration assay was performed using the breast cancer MCF7 and T747D cell lines, and in vivo analysis was performed in rats (Rattus norvegicus). MCF7 and T747D cells were treated with 12.5 µg/mL annonacin coupled with nanodiamonds for 24 and 48 h and further analyzed by MTT, cell migration, and reactive oxygen species (ROS) assays. Twenty-five female rats were divided into five groups. Breast cancer was induced using two intraperitoneal doses of N-nitroso-N-methylurea (NMU) (50 and 30 mg/kg body weight). Annonacin coupled with nanodiamonds was administered by intraperitoneal injection (17.5 mg/kg body weight) for 5 weeks, one injection per 3 days. Results: Administration of annonacin coupled with nanodiamonds significantly reduced MCF7 cell growth and reactive oxygen species (ROS) levels. The in vivo study showed that administration of annonacin coupled with nanodiamonds significantly reduced PI3KCA levels and increased p53 expression, reduced cancer antigen-15-3 (CA-15-3) levels in serum, increased caspase-3 expression, reduced Ki-67 levels, and reduced the thickness of the mammary ductal epithelium. Conclusions: Collectively, this study demonstrated the effectiveness of nanodiamonds as a carrier of annonacin to inhibit breast cancer cell growth through inhibition of the PI3K/Akt signaling pathway.
RESUMO
BACKGROUND: Cancer is a debilitating disease that is on the increase in both developed and developing countries. The plant extract of A. muricata have been known to have a variety of anticancer effects, including anti-angiogenic potential. An in silico study is needed as a preliminary study to understand the mechanism underline this process. OBJECTIVE: The aim of this study was to investigate the potential of the bioactive compounds of A. muricata in regulating angiogenesis process, primarily by the regulation of hypoxia inducible factor (HIF)-1α expression by in silico study. METHODS: This study was performed by in silico analysis including the bioactive compounds preparation, biological activity prediction, protein target and pathway analysis, 3D protein modelling, protein-ligand and protein-protein docking, and the visualization of docking results. RESULTS: There are 3 bioactive compounds of A. muricata with the ability to inhibit HIF-1α expression, including kaempferol, genistein, and glycitein. The inhibition of HIF-1α expression was associated with phosphoinositide 3-kinases (PI3K)/Akt signaling pathway, which involved tyrosine kinase receptor activity on the cell membrane. Based on the silico analysis in this study, we shown that kaempferol, genistein, and glycitein inhibit HIF-1α expression through the disruption of interleukin (IL)-6R and toll-like receptor (TLR)-4 and their respective ligands interaction. CONCLUSION: The findings of this study show that A. muricata bioactive compounds could inhibit HIF-1α expression through disruption of the tyrosine kinase receptor binding with its ligand.
