Cytotoxicity, anti-angiogenic, apoptotic effects and transcript profiling of a naturally occurring naphthyl butenone, guieranone A

Abstract

BackgroundMalignant diseases are responsible of approximately 13% of all deaths each year in the world. Natural products represent a valuable source for the development of novel anticancer drugs. The present study was aimed at evaluating the cytotoxicity of a naphtyl butanone isolated from the leaves of Guiera senegalensis, guieranone A (GA).ResultsThe results indicated that GA was active on 91.67% of the 12 tested cancer cell lines, the IC50 values below 4 μg/ml being recorded on 83.33% of them. In addition, the IC50 values obtained on human lymphoblastic leukemia CCRF-CEM (0.73 μg/ml) and its resistant subline CEM/ADR5000 (1.01 μg/ml) and on lung adenocarcinoma A549 (0.72 μg/ml) cell lines were closer or lower than that of doxorubicin. Interestingly, low cytotoxicity to normal hepatocyte, AML12 cell line was observed. GA showed anti-angiogenic activity with up to 51.9% inhibition of the growth of blood capillaries on the chorioallantoic membrane of quail embryo. Its also induced apotosis and cell cycle arrest. Ingenuity Pathway Analysis identified several pathways in CCRF-CEM cells and functional group of genes regulated upon GA treatment (P < 0.05), the Cell Cycle: G2/M DNA Damage Checkpoint Regulation and ATM Signaling pathways being amongst the four most involved functional groups.ConclusionThe overall results of this work provide evidence of the cytotoxic potential of GA and supportive data for its possible use in cancer chemotherapy.

African Flora Has the Potential to Fight Multidrug Resistance of Cancer

“…The extracts from Xylopia aethiopica , Dorstenia psilirus , Echinops giganteus, and Zingiber officinale strongly inhibited angiogenesis in quail embryo [ 39 ]. A strong antiangiogenic activity on blood capillaries of the chorioallantoic membrane of quail eggs was also reported with compounds such as 16 , 36 , and 17 [ 18 , 57 ].…”

“…(Combretaceae) was active on 11 of 12 cancer cell lines. IC 50 values below 10 μ M were recorded in CCRF-CEM cells (2.31 μ M) and on CEM/ADR5000 cells (3.19 μ M), MCF-7 cells (3.42 μ M), U87MG cells (7.78 μ M), A549 cells (2.28 μ M), HeLa cells (1.61 μ M), and CaSki cells (3.73 μ M) [ 57 ]. In addition to low cross-resistance of CEM/ADR5000 cells, compound 36 was less toxic to the normal hepatocytes AML12 cells, highlighting its selectivity [ 57 ].…”

“…Compounds such as benzophenones 19 , 20 , and 21 demonstrated a very strong induction of apoptosis in leukemia CCRF-CEM cells [ 19 ]; benzophenones 19 and 21 did not induce cell cycle arrest in either G0/G1, S, or M phases, but compound 20 induced arrest in G0/G1 phase [ 19 ]. Flavonoids 22 and 30 as well as pterocarpan isoflavonoids 25 , 28 , and 39 and the naphthyl butenone 36 also induced cell cycle arrest in G0/G1 phase, whilst the isoflavonoid 23 , the acridone alkaloid 44 , induced arrest between G0/G1 and S phases [ 41 , 53 , 54 , 56 , 57 ]. A strong induction of apoptosis was also recorded with 22 , 23 , 25 , and 28 and the xanthone 42 on CCRF-CEM cells [ 53 , 55 ].…”

“…Microarray analysis and signaling pathway profiling identified pathways and possible molecular targets involved in the cytotoxic effect of guieranone A ( 36 ) in leukemia CCRF-CEM cells. Several pathways and biological functions were affected by treatment 36 , including the cell cycle: G2/M DNA damage checkpoint regulation and ATM signaling pathways [ 57 ]. The two most upregulated genes by 36 were HSPA6 (heat shock 70 kDa protein 6) and HIST1H2BD (histone cluster 1, H2bd).…”

Delivering aminopyridine ligands into cancer cells through conjugation to the cell-penetrating peptide BP16

“…This derivative displayed IC 50 values ranging from 4.3 to 5.0 μM against the three cell lines, comparable to those of widely used anticancer drugs such as cisplatin or doxorubicin. 50,51 Moreover, this metal binding conjugate showed an enhanced cytotoxic activity compared to that determined for the (S,S′)-BPBP ligand alone against the same cell lines ( Table 1). These results can be reasoned taken into account the uptake mechanism described for BP16, which internalizes into cancer cells by clathrin-dependent endocytosis being lysosomes the final stage of this pathway.…”