BJ-1108, a 6-Amino-2,4,5-Trimethylpyridin-3-ol Analog, Inhibits Serotonin-Induced Angiogenesis and Tumor Growth through PI3K/NOX Pathway

PloS One
Suhrid BanskotaJung-Ae Kim

Abstract

5-Hydroxytryptamine (5-HT) induces proliferation of cancer cells and vascular cells. In addition to 5-HT production by several cancer cells including gastrointestinal and breast cancer, a significant level of 5-HT is released from activated platelets in the thrombotic environment of tumors, suggesting that inhibition of 5-HT signaling may constitute a new target for antiangiogenic anticancer drug discovery. In the current study we clearly demonstrate that 5-HT-induced angiogenesis was mediated through the 5-HT1 receptor-linked Gβγ/Src/PI3K pathway, but not through the MAPK/ERK/p38 pathway. In addition, 5-HT induced production of NADPH oxidase (NOX)-derived reactive oxygen species (ROS). In an effort to develop new molecularly targeted anticancer agents against 5-HT action in tumor growth, we demonstrate that BJ-1108, a derivative of 6-amino-2,4,5-trimethylpyridin-3-ol, significantly inhibited 5-HT-induced angiogenesis. In addition, BJ-1108 induced a significant reduction in the size and weight of excised tumors in breast cancer cell-inoculated CAM assay, showing proportionate suppression of tumor growth along with inhibition of angiogenesis. In human umbilical vein endothelial cells (HUVECs), BJ-1108 significantly suppressed 5-...Continue Reading

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Citations

Aug 15, 2018·Journal of Cellular Physiology·Hojjat Naderi-Meshkin, Naghmeh Ahmadiankia
Jun 20, 2017·Oxidative Medicine and Cellular Longevity·Magdalena SkoniecznaRafal J Buldak
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May 4, 2020·Digestive Diseases and Sciences·Hoyul LeeJung-Ae Kim
Aug 4, 2020·Bioorganic Chemistry·Chhabi Lal ChaudharyByeong-Seon Jeong
Dec 15, 2020·World Journal of Stem Cells·Gretel Mendoza-AlmanzaJorge Olmos
Aug 21, 2018·Chemico-biological Interactions·Jaya GautamJung-Ae Kim
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Suhrid BanskotaHassan Ashktorab
Aug 4, 2021·Journal of Enzyme Inhibition and Medicinal Chemistry·Bhuwan Prasad AwasthiByeong-Seon Jeong
Sep 3, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sabah HaqWaliul I Khan

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Methods Mentioned

BETA
protein assay
ELISA
fluorescence microscopy

Software Mentioned

GraphPad Prism
Multi Gauge Ver
Image Inside

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