Abstract
Ursolic acid(UA)is a naturally occurring ursane triterpenoid,which exhibits a wide range of unique biological activities.To clarify its mechanism of action(MOA),a series of fluorescent derivatives of UA(5a-c)were designed and synthesized by conjugation with 7-nitrobenzo-2-oxa-1,3-diazole(NBD)fluo-rophore.Among them,5c exhibited similar anti-proliferative activity with UA against HCT116 cells(half maximal inhibitory concentration(IC50)=9.21±0.50 μmol/L).Cell imaging experiment indicated that 5c was rapidly taken up in HCT116 cells in a dose and time-dependent manner.Then,5c was found to lo-calize in endoplasmic reticulum(ER),lysosomes,and mitochondria,but not in nucleus of HCT116 cells by confocal microscopy studies.Preliminary MOA proved that UA induced autophagy with a unique in-tracellular distribution mechanism involving ER and lysosome.In all,our work provides new clues for revealing the molecular mechanism of UA as an antitumor agent.
基金项目
国家重点研发计划(2022YFC3400501)
国家自然科学基金(81825020)
国家自然科学基金(82150208)
Shanghai Science and Technology Commission Biomedical Science and Technology Support Special Project(21S11907900)
Shanghai Science and Technology Commission Biomedical Science and Technology Support Special Project(20S11901000)
National Program for Special Supports of Eminent Professionals()
National Program for Support of Top-notch Young Professionals()
维普
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