Potent anti-cancer effect of 3'-hydroxypterostilbene in human colon xenograft tumors.
Here we report that 3'-hydroxypterostilbene (HPSB), a natural pterostilbene analogue, was more potent than pterostilbene against the growth of human cancer cells (COLO 205, HCT-116, and HT-29) with measured IC50 values of 9.0, 40.2, and 70.9 µM, respectively. We found that HPSB effectively inhibited the growth of human colon cancer cells by inducing apoptosis and autophagy. Autophagy occurred at an early stage and was observed through the formation of acidic vesicular organelles and microtubule-associated protein 1 light chain 3-II production. At the molecular levels, the results from western blot analysis showed that HPSB significantly down-regulated phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinases (MAPKs) signalings including decreased the phosphorylation of mammalian target of rapamycin (mTOR). Significant therapeutic effects were demonstrated in vivo by treating nude mice bearing COLO 205 tumor xenografts with HPSB (10 mg/kg i.p.). These inhibitory effects were accompanied by mechanistic down-regulation of the protein levels of cyclooxygenase-2 (COX-2), matrix metallopeptidase-9 (MMP-9), vascular endothelial growth factor (VEGF), and cyclin D1, as well as by the induction of apoptosis in colon tumors. Our findings suggest that HPSB could serve as a novel promising agent for colon cancer treatment.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Tzu-Chun
TC
Cheng
Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
Ching-Shu
CS
Lai
Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan.
Min-Ching
MC
Chung
Sabinsa Corporation, East Windsor, New Jersey, United States of America.
Nagabhushanam
N
Kalyanam
Sabinsa Corporation, East Windsor, New Jersey, United States of America.
Muhammed
M
Majeed
Department of Food Science, Rutgers University, New Brunswick, New Jersey, United States of America.
Chi-Tang
CT
Ho
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Laboratory Medicine, Taipei Medical University Hospital, Taipei, Taiwan; School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; Comprehensive Cancer Center, Taipei Medical University, Taipei, Taiwan.
Yuan-Soon
YS
Ho
Institute of Food Science and Technology, National Taiwan University, Taipei, Taiwan; Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan.
Min-Hsiung
MH
Pan
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001343:Autophagy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival; D003110:Colonic Neoplasms / Q000188:drug therapy*; D019938:Cyclin D1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D013267:Stilbenes / Q000627:therapeutic use*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
C505072:3'-hydroxypterostilbene; D000970:Antineoplastic Agents; D013267:Stilbenes; D042461:Vascular Endothelial Growth Factor A; D019938:Cyclin D1; C107773:pterostilbene; D051546:Cyclooxygenase 2; D058539:Phosphatidylinositol 3-Kinase; D020780:Matrix Metalloproteinase 9