| Reference | [1]. BMB Rep. 2018 Jun;51(6):302-307. doi: 10.5483/bmbrep.2018.51.6.024.<br />
Pinosylvin exacerbates LPS-induced apoptosis via ALOX 15 upregulation in leukocytes.<br />
Kwon O(1), Seo Y(1), Park H(1).<br />
Author information: (1)Department of Molecular Biology & Institute of Nanosensor and Biotechnology, Dankook University, Cheonan 31116, Korea.<br />
Pinosylvin is known to have anti-inflammatory activity in endothelial cells. In this study, we found that pinosylvin had a pro-apoptotic activity in lipopolysaccharide (LPS)-preconditioned leukocytes. This finding suggests that pinosylvin has an effect on the resolution of inflammation. To understand the detailed mechanism, we examined if pinosylvin enhances cyclooxygenase (COX) or lipoxygenase (LOX) activity in THP-1 and U937 cells. LOX activity was found to be markedly increased by pinosylvin, whereas COX activity was not altered. Furthermore, we found that pinosylvin enhanced both levels of ALOX 15 mRNA and protein, implying that LOX activity, elevated by pinosylvin, is attributed to upregulation of ALOX 15 expression. From this cell signaling study, pinosylvin appeared to promote phosphorylations of ERK and JNK. ERK or JNK inhibitors were found to attenuate ALOX 15 expression and LPS-induced apoptosis promoted by pinosylvin. In conclusion, pinosylvin enhances the apoptosis of LPSpreconditioned leukocytes by up-regulating ALOX 15 expression through ERK and JNK. These findings suggest that pinosylvin may induce the resolution of inflammation. [BMB Reports 2018; 51(6): 302-307].<br />
DOI: 10.5483/bmbrep.2018.51.6.024 PMCID: PMC6033067 PMID: 29555013 [Indexed for MEDLINE]<br />
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[2]. Phytother Res. 2018 Oct;32(10):2097-2104. doi: 10.1002/ptr.6156. Epub 2018 Jul 20.<br />
Pinosylvin enhances leukemia cell death via down-regulation of AMPKα expression.<br />
Song J(1), Seo Y(1), Park H(1).<br />
Author information: (1)Department of Molecular Biology, Institute of Nanosensor and Biotechnology, Dankook University, Chungnam, South Korea.<br />
Resveratrol at high concentrations (50-100 μmol/L) is known to induce cell death in leukemia cells. Here, we investigated whether pinosylvin, a resveratrol analogue, induced cell death in leukemia cells. Cell death was found to be markedly elevated by 50- to 100-μmol/L pinosylvin in THP-1 and U937 cells. It was also shown that pinosylvin induced caspase-3 activation, flip-flop of phosphatidylserine, LC3-II accumulation, LC3 puncta, and p62 degradation in both THP-1 and U937 cells. These data indicate that pinosylvin-induced cell death may occur through apoptosis and autophagy. In addition, we showed that pinosylvin down-regulates AMP-activated protein kinase α1 (AMPKα1) in leukemia cells. Therefore, we correlated AMPKα1 down-regulation and leukemia cell death. AMPKα1 inhibition appeared to decrease pinosylvin-induced apoptosis and autophagy in leukemia cells, implying that AMPK is a key regulator of leukemia cell death. Moreover, we found that both pinosylvin-induced autophagy and apoptotic progress were reduced in AMPKα1-overexpressed leukemia cells, when compared with vector-transfected cells. Cell death was elevated by AMPKα1 overexpression, whereas pinosylvin-induced cell death was markedly decreased by caspase-3 inhibitors or autophagy inhibitors. These results suggest that pinosylvin-induced depletion of AMPKα1 enhances cell death via apoptosis and autophagy in leukemia cells.<br />
DOI: 10.1002/ptr.6156 PMID: 30027566 [Indexed for MEDLINE]<br />
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[3]. Biomed Pharmacother. 2019 Sep;117:109160. doi: 10.1016/j.biopha.2019.109160. Epub 2019 Jul 1.<br />
Pinosylvin reduced migration and invasion of oral cancer carcinoma by regulating matrix metalloproteinase-2 expression and extracellular signal-regulated kinase pathway.<br />
Chen MK(1), Liu YT(2), Lin JT(3), Lin CC(4), Chuang YC(4), Lo YS(4), Hsi YT(4), Hsieh MJ(5).<br />
Author information: (1)Department of Otorhinolaryngology, Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan. (2)Department of Family Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan. (3)Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua 500, Taiwan; School of Medicine, Chung Shan Medical University, Taichung 402, Taiwan. (4)Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan. (5)Institute of Medicine, Chung Shan Medical University, Taichung 402, Taiwan; Department of Holistic Wellness, Mingdao University, Changhua 52345, Taiwan; Oral Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan. Electronic address: [email protected].<br />
BACKGROUND: Pinosylvin possesses several biological properties, including anti-inflammatory, antitumor, and antioxidant characteristics. However, the effects of pinosylvin on the migration and invasion of human oral cancer cells and the underlying mechanisms remain unclear. HYPOTHESIS/PURPOSE: In this research, we investigated the outcome of different concentrations of pinosylvin (0-80 μM) on the metastatic and invasive abilities of SAS, SCC-9, and HSC-3 cells. METHODS AND RESULTS: Western blotting assay and Gelatin zymography assay indicated that pinosylvin inhibited the enzymatic activity of matrix metalloproteinase-2 (MMP-2) and reduced its protein level but increased the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2). Additionally, the wound healing assay and Transwell method showed that pinosylvin reduced the migration of SAS, SCC-9 and HSC-3 oral cancer cells. Besides, pinosylvin decreased the phosphorylation of ERK1/2 protein experssion in both SAS and SCC-9 cells. CONCLUSION: These results indicate that pinosylvin is a potential anticancer agent for preventing oral cancer metastasis.<br />
DOI: 10.1016/j.biopha.2019.109160 PMID: 31387166 [Indexed for MEDLINE]<br />
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[4]. Can J Physiol Pharmacol. 2014 Dec;92(12):993-9. doi: 10.1139/cjpp-2014-0271. Epub 2014 Oct 20.<br />
Pinosylvin at a high concentration induces AMPK-mediated autophagy for preventing necrosis in bovine aortic endothelial cells.<br />
Park J(1), Pyee J, Park H.<br />
Author information: (1)Department of Molecular Biology and Institute of Nanosensor and Biotechnology, Dankook University, 152 Jukjeon-ro, Suji-gu, Yongin-si, Gyeonggi-do 448-701, South Korea.<br />
Pinosylvin is a known functional compound of the Pinus species. Pinosylvin at low concentrations (∼ pmol/L) was reported to promote cell proliferation in endothelial cells. However, this study found that pinosylvin at a high concentration (100 μmol/L) induces cell death in bovine aortic endothelial cells. Therefore, we examined how pinosylvin was associated with apoptosis, autophagy, and necrosis. Pinosylvin at a high concentration appeared to promote caspase-3 activation, nuclear condensation, and the "flip-flop" of phosphatidylserine, indicating that pinosylvin induces apoptosis. However, based on flow cytometry data obtained from double-staining with annexin V and propidium iodide, pinosylvin was shown to inhibit necrosis, a postapoptotic process. Pinosylvin induced LC3 conversion from LC3-I to LC3-II and p62 degradation, which are important indicators of autophagy. In addition, AMP-activated protein kinase (AMPK) appeared to be activated by pinosylvin, and an AMPK inhibitor was markedly shown to reduce the LC3 conversion. The inhibitory effect of an AMPK inhibitor was reversed by pinosylvin. These results suggest that pinosylvin induces autophagy via AMPK activation. Further, necrosis was found to be promoted by an autophagy inhibitor and then restored by pinosylvin, while the caspase-3 inhibitor had no effect on necrosis. These findings indicate that pinosylvin-induced autophagy blocks necrotic progress in endothelial cells.<br />
DOI: 10.1139/cjpp-2014-0271 PMID: 25393712 [Indexed for MEDLINE]<br />
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[5]. Phytother Res. 2013 Apr;27(4):610-7. doi: 10.1002/ptr.4770. Epub 2012 Jun 27.<br />
Pinosylvin induces cell survival, migration and anti-adhesiveness of endothelial cells via nitric oxide production.<br />
Jeong E(1), Lee HR, Pyee J, Park H.<br />
Author information: (1)Department of Molecular Biology, BK21 Graduate Program for RNA Biology, Dankook University, 126 Jukjeon-dong, Suji-gu, Yongin-si, Gyeonggi-do, South Korea.<br />
Pinosylvin is a phenolic compound mainly found in the Pinus species. To determine the vascular functions of pinosylvin, we first examined both proliferation and apoptosis of bovine aortic endothelial cells (BAECs) in the presence of pinosylvin. When BAECs were treated with pinosylvin, etoposide- or starvation-induced apoptosis was shown to be significantly reduced. The anti-apoptotic effect of pinosylvin was mediated by inhibition of caspase-3. Moreover, pinosylvin was shown to activate endothelial nitric oxide synthetase (eNOS). At 1 pM, pinosylvin appeared to have a cell-proliferative effect in the endothelial cell. The pinosylvin-induced cell proliferation was declined by treatment with L-NAME, an eNOS inhibitor. Then, we found that pinosylvin had a stimulatory effect on cell migration and tube formation. These stimulatory effects suggest that pinosylvin is likely to act as a pro-angiogenic factor. Yet another effect of pinosylvin was inhibition of lipopolysaccharide-induced THP-1 cell adhesion to endothelial cells. Altogether, we propose that pinosylvin may be utilized as a phytotherapic agent for the prevention of cardiovascular inflammatory diseases.<br />
DOI: 10.1002/ptr.4770 PMID: 22736379 [Indexed for MEDLINE]
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