Riccardin D-26, a synthesized macrocyclic bisbibenzyl compound, inhibits human oral squamous carcinoma cells KB and KB/VCR: In vitro and in vivo studies

BackgroundRiccardin D-26, a synthesized macrocyclic bisbibenzyl compound, might possess anti-cancer properties. We aimed to evaluate the efficacy of Riccardin D-26 as a candidate compound for treatment of cancers with sensitive or drug resistant cells.MethodsExperiments were performed on human oral squamous carcinoma KB cells and vincristin-selected MDR KB/VCR cells. The inhibition of cell growth was evaluated by colorimetric and clonogenic assays. The apoptotic cells were determined by the Annexin V-FITC/PI staining assay. JC-1 fluorescence probe was used to examine the mitochondria membrane potential (MMP). Further experiments were performed in nude mice bearing KB or KB/VCR xenografts. Riccardin D-26 was administered by injection for 2 weeks. The specimens of KB and KB/VCR xenografts were removed for TUNEL staining and Western blotting analysis.ResultsRiccardin D-26 significantly inhibited cancer growth in both KB and KB/VCR cells. Riccardin D-26's activity in cancer cells was greater than that in human normal liver cells. In mice, Riccardin D-26 effectively prevented the growth of KB and KB/VCR xenografts without significant toxicity. Further studies suggested that Riccardin D-26 inhibited cancer growth by inducing apoptosis in the activation of mitochondria-mediated intrinsic apoptosis pathway. Riccardin D-26 also possessed this activity in regulation of mitogen-related protein kinases such as MAPK and PI3K/Akt, which is associated with its inhibitory effect on KB/VCR cells.ConclusionsRiccardin D-26 possessed an anti-proliferation activity against both sensitive KB and MDR KB/VCR cancer cells.General significanceRiccardin D-26 could be a promising agent for treatment of cancers with sensitive or drug resistant cells.

► Riccardin D-26 is a derivative of the synthesized macrocyclic bisbibenzyl compound.
► Riccardin D-26 possessed activity against both KB and KB/VCR cells.
► Riccardin D-26 inhibited cancer growth in mice with no significant toxicity.
► The effect of Riccardin D-26 on KB/VCR cells was due to induction of apoptosis.
► Riccardin D-26 possessed the activity in regulation of MAPK and PI3K/Akt.