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

Venu Sharma, Arem Qayum, Sanjana Kaul, Ajeet Singh, Kamal K Kapoor, Debaraj Mukherjee, Shashank K Singh, Manoj K Dhar

ACS Omega. 2019 Nov 26;4(24):20435-20442.

PMID: 31858026

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP27215141 Neoandrographolide Neoandrographolide 27215-14-1 Price
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