Oral Cancer

Expert Opin Ther Targets.2014 Oct;18(10):1109-20. doi: 10.1517/14728222.2014.947962. Epub 2014 Aug 9.

Pterostilbenesuppresses oral cancer cell invasion by inhibiting MMP-2 expression.

Lin CW¹,Chou YE, Chiou HL, Chen MK, Yang WE, Hsieh MJ, Yang SF.

Abstract

OBJECTIVE: Polyphenol compounds, present in a wide variety of natural plants, exhibit antioxidant and free radical scavenging ability and induce apoptosis in various cancer cells. However, the effect of pterostilbene on oral cancer cell metastasis has not been clarified.

RESEARCH DESIGN AND METHODS: The present study aimed to examine the anti-metastatic properties of pterostilbene in human oral squamous cell carcinoma (SCC)-9 cells.

RESULTS: In this study, pterostilbene treatment significantly inhibited migration/invasion capacities of SCC-9 cells in vitro. The results of zymography and western blotting revealed that the activities and protein levels of the MMP-2 and urokinase-type plasminogen activator (u-PA) was inhibited by pterostilbene. Western blot analysis also showed that pterostilbene inhibits the phosphorylation of Akt, extracellular signal-regulated kinase 1/2 and p38. Determinations of the mRNA levels, real-time polymerase chain reaction and promoter assays were conducted to evaluate the inhibitory effects of pterostilbene on MMP-2 and u-PA expression in SCC-9 cells. Such inhibitory effects were associated with the upregulation of tissue inhibitor of metalloproteinase-2, plasminogen activator inhibitor-1 and the downregulation of the transcription factors of NF-κB, SP-1 and CREB signaling pathways.

CONCLUSIONS: Pterostilbene may have potential use as a chemopreventive agent against oral cancer metastasis.

KEYWORDS: MMP-2; migration; oral cancer; pterostilbene; urokinase-type plasminogen activator

PMID: 25109417

Oral Oncol.2015 Jun;51(6):593-601. doi: 10.1016/j.oraloncology.2015.03.007. Epub 2015 Apr 14.

Pterostilbene induce autophagy on human oral cancercells through modulation of Akt and mitogen-activated protein kinase pathway.

Ko CP¹,Lin CW², Chen MK³, Yang SF⁴, Chiou HL⁵, Hsieh MJ⁶.

Author information

Abstract

OBJECTIVES: Extensive research supports the administration of herbal medicines or natural foods during cancer therapy. Pterostilbene, a naturally occurring phytoalexin, has various pharmacological activities, including antioxidant activity, cancer prevention activity, and cytotoxicity to many cancers. However, the effect of pterostilbene on the autophagy of tumor cells has not been clarified.

MATERIALS AND METHODS: In this study, the unique effects of pterostilbene on the autophagy of human oral cancer cells were investigated.

RESULTS: The results of this study showed that pterostilbene effectively inhibited the growth of human oral cancer cells by inducing cell cycle arrest and apoptosis. In addition, the formation of acidic vesicular organelles and LC3-II production also demonstrated that pterostilbene induced autophagy. Administering 3-methylamphetamine (3-MA) and bafilomycin A1 (BafA1) exerted differing effects on the pterostilbene-induced death of human oral cancer cells. Pterostilbene-induced autophagy was triggered by activation of JNK1/2 and inhibition of Akt, ERK1/2, and p38.

CONCLUSION: In conclusion, this study demonstrated that pterostilbene caused autophagy and apoptosis in human oral cancer cells, suggesting that pterostilbene could serve as a new and promising agent for treating human oral cancer.

KEYWORDS: Apoptosis; Autophagy; MAPK; Oral cancer; Phytoalexin; Pterostilbene

PMID: 25883032

PLoS One.2015 Nov 4;10(11):e0141719. doi: 10.1371/journal.pone.0141719. eCollection 2015.

Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine.

Bundela S^1,2, Sharma A², Bisen PS^1,3.

Author information

Abstract

Oral cancer is one of the main causes of cancer-related deaths in South-Asian countries. There are very limited treatment options available for oral cancer. Research endeavors focused on discovery and development of novel therapies for oral cancer, is necessary to control the ever rising oral cancer related mortalities. We mined the large pool of compounds from the publicly available compound databases, to identify potential therapeutic compounds for oral cancer. Over 84 million compounds were screened for the possible anti-cancer activity by custom build SVM classifier. The molecular targets of the predicted anti-cancer compounds were mined from reliable sources like experimental bioassays studies associated with the compound, and from protein-compound interaction databases. Therapeutic compounds from DrugBank, and a list of natural anti-cancer compounds derived from literature mining of published studies, were used for building partial least squares regression model. The regression model thus built, was used for the estimation of oral cancer specific weights based on the molecular targets. These weights were used to compute scores for screening the predicted anti-cancer compounds for their potential to treat oral cancer. The list of potential compounds was annotated with corresponding physicochemical properties, cancer specific bioactivity evidences, and literature evidences. In all, 288 compounds with the potential to treat oral cancer were identified in the current study. The majority of the compounds in this list are natural products, which are well-tolerated and have minimal side-effects compared to the synthetic counterparts. Some of the potential therapeutic compounds identified in the current study are resveratrol, nimbolide, lovastatin, bortezomib, vorinostat, berberine, pterostilbene, deguelin, andrographolide, and colchicine.

PMID: 26536350

Cell Physiol Biochem.2016;38(3):1226-44. doi: 10.1159/000443071. Epub 2016 Mar 17.

PterostilbeneInhibits the Growth of Human Esophageal Cancer Cells by Regulating Endoplasmic Reticulum Stress.

Feng Y, Yang Y, Fan C, Di S, Hu W, Jiang S, Li T, Ma Z, Chao D, Feng X, Xin Z, Pang S, Li X, Yan X.

Abstract

BACKGROUND/AIMS: Pterostilbene(PTE), a natural dimethylated resveratrol analog from blueberries, is known to have diverse pharmacological activities, including anticancer properties. In this study, we investigated the anticancer activity of PTE against human esophageal cancer cells both in vitro and in vivo and explored the role of endoplasmic reticulum (ER) stress (ERS) signaling in this process.

METHODS: Cell viability, the apoptotic index, Caspase 3 activity, adhesion, migration, reactive oxygen species (ROS) levels, and glutathione (GSH) levels were detected to explore the effect of PTE on human EC109 esophageal cancer cells. Furthermore, siRNA transfection and a chemical inhibitor were employed to confirm the role of ERS.

RESULTS: PTE treatment dose- and time-dependently decreased the viability of human esophageal cancerEC109 cells. PTE also decreased tumor cell adhesion, migration and intracellular GSH levels while increasing the apoptotic index, Caspase 3 activity and ROS levels, which suggest the strong anticancer activity of PTE. Furthermore, PTE treatment increased the expression of ERS-related molecules (GRP78, ATF6, p-PERK, p-eIF2α and CHOP), upregulated the pro-apoptosis-related protein PUMA and downregulated the anti-apoptosis-related protein Bcl-2 while promoting the translocation of cytochrome c from mitochondria to cytosol and the activation of Caspase 9 and Caspase 12. The downregulation of ERS signaling by CHOP siRNA desensitized esophageal cancer cells to PTE treatment, whereas upregulation of ERS signaling by thapsigargin (THA) had the opposite effect. N-Acetylcysteine (NAC), a ROS scavenger, also desensitized esophageal cancer cells to PTE treatment.

CONCLUSIONS: Overall, the results indicate that PTE is a potent anti-cancer pharmaceutical against human esophageal cancer, and the possible mechanism involves the activation of ERS signaling pathways.

PMID: 26982591