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Potent anti-cancer effect of 3'-hydroxypterostilbene in human colon xenograft tumors.

Cheng TC, Lai CS, Chung MC, Kalyanam N, Majeed M, Ho CT, Ho YS, Pan MH - PLoS ONE (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
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.

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Chemical structure of pterostilbene and 3′-hydroxypterostilbene.
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pone-0111814-g001: Chemical structure of pterostilbene and 3′-hydroxypterostilbene.

Mentions: Pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene), a dimethylether analogue of resveratrol, is found to be as effective as resveratrol in preventing carcinogen-induced preneoplastic lesions in a mouse mammary culture model and inhibits metastatic growth of melanoma cells to the liver [7], [8]. We and others have shown that pterostilbene exhibits pleiotropic pharmacological effects including anti-inflammatory, antioxidant, anti-proliferative, anti-cancer, and pain-relieving activities in cell culture and animal studies [9]–[14]. Recently, 3′-hydroxypterostilbene (Fig. 1), a new natural pterostilbene analogue has been isolated from Sphaerophysa salsula, is markedly more active than pterostilbene in inducing apoptosis in sensitive and resistant leukemia cells [15], [16]. However, the in vivo antitumor effect of HPSB remains unclear.


Potent anti-cancer effect of 3'-hydroxypterostilbene in human colon xenograft tumors.

Cheng TC, Lai CS, Chung MC, Kalyanam N, Majeed M, Ho CT, Ho YS, Pan MH - PLoS ONE (2014)

Chemical structure of pterostilbene and 3′-hydroxypterostilbene.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4229093&req=5

pone-0111814-g001: Chemical structure of pterostilbene and 3′-hydroxypterostilbene.
Mentions: Pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene), a dimethylether analogue of resveratrol, is found to be as effective as resveratrol in preventing carcinogen-induced preneoplastic lesions in a mouse mammary culture model and inhibits metastatic growth of melanoma cells to the liver [7], [8]. We and others have shown that pterostilbene exhibits pleiotropic pharmacological effects including anti-inflammatory, antioxidant, anti-proliferative, anti-cancer, and pain-relieving activities in cell culture and animal studies [9]–[14]. Recently, 3′-hydroxypterostilbene (Fig. 1), a new natural pterostilbene analogue has been isolated from Sphaerophysa salsula, is markedly more active than pterostilbene in inducing apoptosis in sensitive and resistant leukemia cells [15], [16]. However, the in vivo antitumor effect of HPSB remains unclear.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.

ABSTRACT
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.

Show MeSH
Related in: MedlinePlus