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Carbohydrate Modifications of Neoandrographolide for Improved Reactive Oxygen Species-Mediated Apoptosis through Mitochondrial Pathway in Colon Cancer

[Image: see text] Modifications at the carbohydrate moiety of neoandrographolide, isolated from the medicinal plant Andrographis paniculata, result in more potent and less toxic derivatives, namely, 4′,6′-benzylidene neoandrographolide (2b) and 4′6′-p-methoxybenzylidene neoandrographolide (2c). Thes...

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Detalles Bibliográficos
Autores principales: Sharma, Venu, Qayum, Arem, Kaul, Sanjana, Singh, Ajeet, Kapoor, Kamal K., Mukherjee, Debaraj, Singh, Shashank K., Dhar, Manoj K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6906770/
https://www.ncbi.nlm.nih.gov/pubmed/31858026
http://dx.doi.org/10.1021/acsomega.9b01249
Descripción
Sumario:[Image: see text] Modifications at the carbohydrate moiety of neoandrographolide, isolated from the medicinal plant Andrographis paniculata, result in more potent and less toxic derivatives, namely, 4′,6′-benzylidene neoandrographolide (2b) and 4′6′-p-methoxybenzylidene neoandrographolide (2c). These showed improved cytotoxicity against SW-620, PC-3, and A549 cancer cell lines. Nuclear morphology studies were conducted on compound 2b by 4′,6-diamidino-2-phenylidole staining and detection of intracellular reactive oxygen species (ROS) accumulation. It showed an increase in the generation of cellular and mitochondrial ROS level. The probable relation of B-cell lymphoma-2 (Bcl-2, an apoptosis inhibitor) to B-cell lymphoma-2-associated X protein (Bax, an apoptosis promoter) ratio with caspase-3 (apoptosis coordination enzyme) in the colon cancer cell line SW-620 was investigated, and it was discovered that upon 2b treatment, the expression of caspase-3 Bax increased remarkably. However, in 2b-treated cells, the expression of Bcl-2 was downregulated as compared to untreated cells.