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TGFβ1 induces stress fiber formation through upregulation of TRPC6 in vascular smooth muscle cells
Park, Soonbum,Lee, Sanghoon,Park, Eun-Jung,Kang, MinJi,So, Insuk,Jeon, Ju-Hong,Chun, Jung Nyeo Elsevier 2017 Biochemical and biophysical research communication Vol.483 No.1
<P><B>Abstract</B></P> <P>Aberrant transforming growth factor β1 (TGFβ1) signaling plays a crucial role in the pathogenesis of vascular fibrosis. On the other hand, deregulated transient receptor potential canonical 6 (TRPC6) channel expression shows impaired vascular physiology and wound healing. However, it has little been known about the functional association between TGFβ1 and TRPC6 in vascular smooth muscle cells (VSMCs). In this study, we analyzed the microarray data obtained from TGFβ1-treated A7r5 VSMCs. We found that TGFβ1 specifically elevates the expression level of TRPC6 mainly through Smad-dependent canonical pathway. The siRNA against TRPC6 abolished TGFβ1-induced molecular and cellular phenotype changes, including myosin light chain phosphorylation, actin stress fiber formation, and cell migration. These results demonstrate that TRPC6 is an important component of TGFβ1 signaling pathway in VSMCs. Therefore, our findings provide a basis for future investigation aimed at developing novel therapeutic strategies for treatment of vascular fibrosis.</P> <P><B>Highlights</B></P> <P> <UL> <LI> TGFβ1 specifically elevates the expression level of TRPC6. </LI> <LI> TGFβ1 upregulates TRPC6 mainly through Smad-dependent canonical pathway. </LI> <LI> TRPC6 plays a crucial role in TGFβ1-induced stress fiber formation and cell migration. </LI> </UL> </P>
Park Soonbum,Cho Eun A,Chun Jung Nyeo,Lee Da Young,Lee Sanghoon,Kim Mi Yeon,Bae Sang Mun,Jo Su In,Lee So Hee,Park Hyun Ho,김태민,So Insuk,Kim Sang-Yeob,Jeon Ju-Hong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Crizotinib is a clinically approved tyrosine kinase inhibitor for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring EML4-ALK fusion. Crizotinib was originally developed as an inhibitor of MET (HGF receptor), which is involved in the metastatic cascade. However, little is known about whether crizotinib inhibits tumor metastasis in NSCLC cells. In this study, we found that crizotinib suppressed TGFβ signaling by blocking Smad phosphorylation in an ALK/MET/RON/ROS1-independent manner in NSCLC cells. Molecular docking and in vitro enzyme activity assays showed that crizotinib directly inhibited the kinase activity of TGFβ receptor I through a competitive inhibition mode. Cell tracking, scratch wound, and transwell migration assays showed that crizotinib simultaneously inhibited TGFβ- and HGF-mediated NSCLC cell migration and invasion. In addition, in vivo bioluminescence imaging analysis showed that crizotinib suppressed the metastatic capacity of NSCLC cells. Our results demonstrate that crizotinib attenuates cancer metastasis by inhibiting TGFβ signaling in NSCLC cells. Therefore, our findings will help to advance our understanding of the anticancer action of crizotinib and provide insight into future clinical investigations.
Asymmetric Total Synthesis of (+)-Intricenyne via an Endocyclization Route to Oxocane Skeleton
Ahn, Jungmin,Lim, Changjin,Yun, Hwayoung,Kim, Hyun Su,Kwon, Soonbum,Lee, Jeeyeon,Lee, Seungbeom,An, Hongchan,Park, Hyeong-geun,Suh, Young-Ger American Chemical Society 2017 Organic letters Vol.19 No.24
<P>The first total synthesis of (+)-intricenyne consisting of an oxocane skeleton was achieved via an extremely selective endocyclization strategy. The key features of the synthesis include a regio- and diastereoselective epoxide opening reaction, concise elaboration of oxocane cores via abnormally selective endocyclization ether ring formation, and versatile incorporation of the labile functional groups.</P><P><B>Graphic Abstract</B> <IMG SRC='http://pubs.acs.org/appl/literatum/publisher/achs/journals/content/orlef7/2017/orlef7.2017.19.issue-24/acs.orglett.7b03370/production/images/medium/ol-2017-033705_0007.gif'></P><P><A href='http://pubs.acs.org/doi/suppl/10.1021/ol7b03370'>ACS Electronic Supporting Info</A></P>
Panaxynol, a natural Hsp90 inhibitor, effectively targets both lung cancer stem and non-stem cells
Le, Huong Thuy,Nguyen, Huy Truong,Min, Hye-Young,Hyun, Seung Yeob,Kwon, Soonbum,Lee, Yeongcheol,Le, Thi Hong Van,Lee, Jeeyeon,Park, Jeong Hill,Lee, Ho-Young Elsevier 2018 Cancer letters Vol.412 No.-
<P><B>Abstract</B></P> <P>Cancer stem-like cells (CSCs) contribute to tumor recurrence and chemoresistance. Hence, strategies targeting CSCs are crucial for effective anticancer therapies. Here, we demonstrate the capacities of the non-saponin fraction of <I>Panax ginseng</I> and its active principle panaxynol to inhibit Hsp90 function and viability of both non-CSC and CSC populations of NSCLC <I>in vitro</I> and <I>in vivo.</I> Panaxynol inhibited the sphere forming ability of NSCLC CSCs at nanomolar concentrations, and micromolar concentrations of panaxynol suppressed the viability of NSCLC cells (non-CSCs) and their sublines carrying acquired chemoresistance with minimal effect on normal cells derived from various organs. Orally administered panaxynol significantly reduced lung tumorigenesis in <I>Kras</I> <SUP> <I>G12D/+</I> </SUP> transgenic mice and mice carrying NSCLC xenografts without detectable toxicity. Mechanistically, panaxynol disrupted Hsp90 function by binding to the N-terminal and C-terminal ATP-binding pockets of Hsp90 without increasing Hsp70 expression. These data suggest the potential of panaxynol as a natural Hsp90 inhibitor targeting both the N-terminal and C-terminal of Hsp90 with limited toxicities.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Panaxynol inhibited the sphere-forming ability of NSCLC CSCs by inducing apoptosis. </LI> <LI> Panaxynol suppressed the viability of NSCLC cells with no effects on normal cells. </LI> <LI> Panaxynol significantly reduced lung tumorigenesis without detectable toxicity. </LI> <LI> Panaxynol interacted with the N- and C-terminal ATP binding pockets of Hsp90. </LI> <LI> Panaxynol disrupted Hsp90 function without inducing Hsp70 expression. </LI> </UL> </P>
OH, EUN-GYOUNG,SON, KWANG-TAE,YU, HONGSIK,LEE, TAE-SEEK,LEE, HEE-JUNG,SHIN, SOONBUM,KWON, JI-YOUNG,PARK, KUNBAWUI,KIM, JIHOE International Association for Food Protection 2011 Journal of food protection Vol.74 No.3
<P>The antimicrobial resistance patterns to 15 antimicrobial agents of Vibrio parahaemolyticus and Vibrio alginolyticus isolated from farmed fishes, including olive flounder (Paralichthys olivaceus), black rockfish (Sebastes schlegeli), red sea bream (Pagrus major), and sea bass (Lateolabrax japonicus), were investigated from 2005 through 2007. A total of 218 V. parahaemolyticus isolates and 153 V. alginolyticus isolates were obtained from the 180 fish samples collected from fish farms located along the southern coast of Korea. We found that 65.1% of V. parahaemolyticus and 85.6% of V. alginolyticus isolates showed antimicrobial resistance against more than one antimicrobial agent. The prevalence of resistance in V. parahaemolyticus isolates to ampicillin was highest (57.8%), followed by resistance to rifampin (11.9%), streptomycin (8.7%), and trimethoprim (6.4%). V. alginolyticus isolates were also most resistant to ampicillin (75.2%), followed by tetracycline (15.0%), trimethoprim (12.4%), and rifampin (9.8%). The prevalence of multiresistance to four or more antimicrobials was higher in V. alginolyticus (11.1%) than in V. parahaemolyticus (5%). Antimicrobial resistance rates per isolate of V. parahaemolyticus and V. alginolyticus possessing virulence genes were not different from those of the rest of the isolates.</P>