A potent betulinic acid analogue ascertains an antagonistic mechanism between autophagy and proteasomal degradation pathway in HT-29 cells

BMC Cancer
Debasmita DuttaPadma Das

Abstract

Betulinic acid (BA), a member of pentacyclic triterpenes has shown important biological activities like anti-bacterial, anti-malarial, anti-inflammatory and most interestingly anticancer property. To overcome its poor aqueous solubility and low bioavailability, structural modifications of its functional groups are made to generate novel lead(s) having better efficacy and less toxicity than the parent compound. BA analogue, 2c was found most potent inhibitor of colon cancer cell line, HT-29 cells with IC50 value 14.9 μM which is significantly lower than standard drug 5-fluorouracil as well as parent compound, Betulinic acid. We have studied another mode of PCD, autophagy which is one of the important constituent of cellular catabolic system as well as we also studied proteasomal degradation pathway to investigate whole catabolic pathway after exploration of 2c on HT-29 cells. Mechanism of autophagic cell death was studied using fluorescent dye like acridine orange (AO) and monodansylcadaverin (MDC) staining by using fluorescence microscopy. Various autophagic protein expression levels were determined by Western Blotting, qRT-PCR and Immunostaining. Confocal Laser Scanning Microscopy (CLSM) was used to study the colocalization of...Continue Reading

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Citations

Sep 7, 2016·Ageing Research Reviews·Yan YinDandan Sun
Nov 5, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Runlan LuoZeyao Tang
May 28, 2019·Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology·Xubin YinSonglin Wang
Jun 10, 2020·BMC Complementary Medicine and Therapies·Yangyang GuoLinxiao Sun
Jul 1, 2020·Recent Patents on Anti-cancer Drug Discovery·Javad Saffari-ChaleshtoriSayed Mohammad Shafiee
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kian Chung ChokSoi Moi Chye

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Methods Mentioned

BETA
ELISA
fluorescence microscopy
electrophoresis
PCR
transmission electron microscopy
Assay
flow cytometry
confocal microscopy
Scanning Microscopy
Fluorescence

Software Mentioned

Origin
Image J
Graph Pad Prism
GraphPad

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