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

• Published in: Biochimica et biophysica acta Vol. 1830; no. 1; pp. 2194 - 2203
• Main Authors: Yue, Bin, Zhao, Cui-Rong, Xu, Hui-Min, Li, Yuan-Yuan, Cheng, Yan-Na, Ke, Han-Ni, Yuan, Yi, Wang, Rui-Qi, Shi, Yan-Qiu, Lou, Hong-Xiang, Qu, Xian-Jun
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.01.2013
• Subjects: Animals; Annexin A5 - metabolism; antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; apoptosis; carcinoma; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; cell growth; Cell Line, Tumor; colorimetry; drug resistance; Drug Resistance, Neoplasm - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; fluorescence; hepatocytes; Humans; in vivo studies; KB/VCR; Macrocyclic Compounds - chemical synthesis; Macrocyclic Compounds - chemistry; Macrocyclic Compounds - pharmacology; MAPK; MDR; membrane potential; Membrane Potential, Mitochondrial - drug effects; Mice; Mice, Nude; Mitochondria - metabolism; Mitochondria - pathology; Mitochondria-mediated intrinsic apoptosis pathway; mitochondrial membrane; Mitochondrial Membranes - metabolism; Mitochondrial Membranes - pathology; mitogen-activated protein kinase; Mouth Neoplasms - drug therapy; Mouth Neoplasms - metabolism; Mouth Neoplasms - pathology; neoplasm cells; Phenyl Ethers - chemical synthesis; Phenyl Ethers - chemistry; Phenyl Ethers - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; PI3K/Akt; Proto-Oncogene Proteins c-akt - metabolism; Stilbenes - chemical synthesis; Stilbenes - chemistry; Stilbenes - pharmacology; Synthesized macrocyclic bisbibenzyl compound; toxicity; Western blotting; Xenograft Model Antitumor Assays; Synthesized macrocyclic bisbibenzyl compound; KB/VCR; MDR; MAPK; Mitochondria-mediated intrinsic apoptosis pathway; PI3K/Akt
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2012.10.011

Riccardin 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. Experiments 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 2weeks. The specimens of KB and KB/VCR xenografts were removed for TUNEL staining and Western blotting analysis. Riccardin 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. Riccardin D-26 possessed an anti-proliferation activity against both sensitive KB and MDR KB/VCR cancer cells. Riccardin 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.