Capsaicin Inhibited Aggressive Phenotypes through Downregulation of Tumor-Associated NADH Oxidase (tNOX) by POU Domain Transcription Factor POU3F2.
Capsaicin has been reported to preferentially inhibit the activity of tumor-associated NADH oxidase (tNOX), which belongs to a family of growth-related plasma membrane hydroquinone oxidases in cancer/transformed cells. The inhibitory effect of capsaicin on tNOX is associated with cell growth attenuation and apoptosis. However, no previous study has examined the transcriptional regulation of tNOX protein expression. Bioinformatic analysis has indicated that the tNOX promoter sequence harbors a binding motif for POU3F2, which is thought to play important roles in neuronal differentiation, melanocytes growth/differentiation and tumorigenesis. In this study, we found that capsaicin-mediated tNOX downregulation and cell migration inhibition were through POU3F2. The protein expression levels of POU3F2 and tNOX are positively correlated, and that overexpression of POU3F2 (and the corresponding upregulation of tNOX) enhanced the proliferation, migration and invasion in AGS (human gastric carcinoma) cells. In contrast, knockdown of POU3F2 downregulates tNOX, and the cancer phenotypes are affected. These findings not only shed light on the molecular mechanism of the anticancer properties of capsaicin, but also the transcription regulation of tNOX expression that may potentially explain how POU3F2 is associated with tumorigenesis.
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. p311308@hotmail.com.
Hung Yen
HY
Chen
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. cornsugar@gmail.com.
Yi Hui
YH
Lee
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. trista09081123@gmail.com.
Huei Yu
HY
Chen
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. r.leafage000@gmail.com.
Chia An
CA
Yeh
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. pjchueh@dragon.nchu.edu.tw.
Pin Ju
PJ
Chueh
Institute of Biomedical Sciences, National Chung Hsing University, Taichung 40227, Taiwan. ymjlin@dragon.nchu.edu.tw.
Yi-Mei J
YM
Lin
D002211:Capsaicin / Q000008:administration & dosage*; D063646:Carcinogenesis / Q000235:genetics; D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D008544:Melanocytes / Q000378:metabolism / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D050809:POU Domain Factors / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D018398:Homeodomain Proteins; D050809:POU Domain Factors; C085076:transcription factor Brn-2; D009247:NADH, NADPH Oxidoreductases; C431909:tumor-associated NADH oxidase; D002211:Capsaicin
POU3F2-binding motif; cancer; transcriptional regulation; tumor-associated NADH oxidase (tNOX)