Quinovic acid purified from medicinal plant Fagonia indica mediates anticancer effects via death receptor 5
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Quinovic acid purified from medicinal plant Fagonia indica mediates anticancer effects via death receptor 5 Asma Umer Khayam1,2 · Harsh Patel1 · Nicholas A. Faiola1 · Andre E. Figueroa Milla1 · Erum Dilshad3 · Bushra Mirza2 · Ying Huang1 · M. Saeed Sheikh1 Received: 1 June 2020 / Accepted: 17 July 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Plants are major source for discovery and development of anticancer drugs. Several plant-based anticancer drugs are currently in clinical use. Fagonia indica is a plant of medicinal value in the South Asian countries. Using mass spectrometry and NMR spectroscopy, several compounds were purified from the F. indica extract. We have used one of the purified compounds quinovic acid (QA) and found that QA strongly suppressed the growth and viability of human breast and lung cancer cells. QA did not inhibit growth and viability of non-tumorigenic breast cells. QA mediated its anticancer effects by inducing cell death. QA-induced cell death was associated with biochemical features of apoptosis such as activation of caspases 3 and 8 as well as PARP cleavage. QA also upregulated mRNA and protein levels of death receptor 5 (DR5). Further investigation revealed that QA did not alter DR5 gene promoter activity, but enhanced DR5 mRNA and protein stabilities. DR5 is one of the major components of the extrinsic pathway of apoptosis. Accordingly, Apo2L/TRAIL, the DR5 ligand, potentiated the anticancer effects of QA. Our results indicate that QA mediates its anticancer effects, at least in part, by engaging DR5depentent pathway to induce apoptosis. Based on our results, we propose that QA in combination with Apo2L/TRAIL can be further investigated as a novel therapeutic approach for breast and lung cancers. Keywords Natural product · Breast cancer · Lung cancer · Quinovic acid · DR5 · Apo2L/TRAIL
Introduction Plants from land and aquatic sources have proven to be a rich source for the discovery and development of anticancer drugs. The agents isolated from these natural sources generally fall under a variety of groups including diterpenes, diterpenoquinone, lactonic sesquiterpene, alkaloids, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11010-020-03841-4) contains supplementary material, which is available to authorized users. * M. Saeed Sheikh [email protected] 1
Department of Pharmacology, State University of New York (SUNY), Upstate Medical University, 750 E Adams St, Syracuse, NY 13210, USA
2
Department of Biochemistry, Faculty of Biological Sciences, Quaid-I-Azam University, Islamabad, Pakistan
3
Department of Bioinformatics and Biosciences, Faculty of Health and Life Sciences, Capital University of Science and Technology, Islamabad, Pakistan
macrocyclic polyethers, proteins, purine-related compounds, peptides, cyclic depsipeptide and similar others [1]. Several important anticancer drugs currently in the clinic have their origins linked to plants. For example (1) vinca alkaloid
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