Prooxidative activity of plumbagin induces apoptosis in human pancreatic ductal adenocarcinoma cells via intrinsic apoptotic pathway. (June 2020)

• Record Type: Journal Article
• Authors: Pandey, Kamal; Tripathi, Surya Kant; Panda, Munmun; Biswal, Bijesh K.
• Is Part Of: Toxicology in vitro. Volume 65(2020)
• Publication Date: 2020-06
• Subjects: Pancreatic cancer -- Plumbagin -- Apoptosis -- Reactive oxygen species -- Caspases; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2020.104788
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Prognosis of pancreatic cancer patients remains extremely poor thus, the need for the development of new therapeutic options is crucial. Plumbagin, a naphthoquinone derivative from Plumbago indica has been found to possess various pharmacological properties including anticancer activity. The present study was designed to investigate the inhibitory potential of plumbagin and associated mechanisms in pancreatic cancer cells. Fluorescence and flow cytometric analysis exhibited an increased percentage of apoptotic cells in both monolayer culture and 3D tumor spheroids. Upon plumbagin treatment, reactive oxygen species content of the cancer cells escalated and prompted alleviation of the mitochondrial membrane potential, which triggers caspase-dependent apoptosis. Interestingly, N -acetylcysteine inhibited the plumbagin induced apoptosis. We also found that the expression of Bcl-2 protein decreased and the expression of Bax protein increased. Moreover, plumbagin treatment led to upregulation of cleaved caspase-3 and caspase-9. These results support the views that plumbagin induced stress signals by damaging mitochondria and induce ROS mediated apoptosis via intrinsic apoptotic signaling in pancreatic cancer cells. To summarize, our study suggests that plumbagin may be utilized as a future anti-cancer therapy agent against pancreatic cancer, which is a major threat owing to its stubborn intransigence towards current treatment regimens. Graphical abstract: Unlabelled Image Highlights: Plumbagin inhibited the proliferation of 2D and 3D cultured pancreatic cancer cells. Plumbagin aggravated ROS and alleviated MMP. Elimination of ROS production inhibited apoptosis mediated by plumbagin. It activated mitochondrial-mediated pathways of apoptosis.