Cytostatic and Cytotoxic Natural Products against Cancer Cell Models

Abstract

The increasing prevalence of drug resistant and/or high-risk cancers indicate further drug discovery research is required to improve patient outcome. This study outlines a simplified approach to identify lead compounds from natural products against several cancer cell lines, and provides the basis to better understand structure activity relationship of the natural product cephalotaxine. Using high-throughput screening, a natural product library containing fractions and pure compounds was interrogated for proliferation inhibition in acute lymphoblastic leukemia cellular models (SUP-B15 and KOPN-8). Initial hits were verified in control and counter screens, and those with EC50 values ranging from nanomolar to low micromolar were further characterized via mass spectrometry, NMR, and cytotoxicity measurements. Most of the active compounds were alkaloid natural products including cephalotaxine and homoharringtonine, which were validated as protein synthesis inhibitors with significant potency against several cancer cell lines. A generated BODIPY-cephalotaxine probe provides insight into the mode of action of cephalotaxine and further rationale for its weaker potency when compared to homoharringtonine. The steroidal natural products (ecdysone and muristerone A) also showed modest biological activity and protein synthesis inhibition. Altogether, these findings demonstrate that natural products continue to provide insight into structure and function of molecules with therapeutic potential against drug resistant cancer cell models.

In Vitro Anticancer Drug Sensitivity Sensing through Single-Cell Raman Spectroscopy

“…This agreed well with the results from populational analysis and other studies that use the MTT assay [27,[31][32][33][34]. The CTG kit used here is a derivative of the MTT assay-a gold-standard approach for in vitro drug efficacy identification [35]. In short, our results from a panel of eight drugs on two cancer cell lines demonstrated that single-cell Raman-DIP could track the variation of cellular metabolic activity and could also shorten a lengthy 72-144 h in vitro drug sensitivity test procedure to 48 h. Hence, this reduction in time potentially lowers the cost for drug screening and speeds up the process for determining the correct cancer treatment for individuals.…”

Evaluation of the In Vitro Cytotoxic Activity of Ursolic Acid PLGA Nanoparticles against Pancreatic Ductal Adenocarcinoma Cell Lines

“…Consequently, there is much work to do in term of developing new drugs and therapies against PDAC, especially to achieve complete remission or cure. One key strategy for such an aggressive disease is to use naturally-derived compounds that possess a wide spectrum of anticancer activities that help to overcome multidrug resistance [ 40 , 41 ], prevent metastasis [ 42 ], inhibit precancerous signaling pathways [ 43 , 44 , 45 ], or possess direct cytotoxic effects towards cancer cells [ 46 , 47 ]. Unfortunately, many of these types of naturally-derived compounds also show poor bioavailability, due to their highly hydrophobic nature which, in turn, disqualifies them for direct intravenous usage without specific formulation [ 48 ].…”

Crocin treatment promotes the oxidative stress and apoptosis in human thyroid cancer cells FTC‐133 through the inhibition of STAT/JAK signaling pathway

“…Cytotoxic is demarcated as a cell necrotizing capacity of a composite free from the cell death pathways. [ 19 ] MTT test is a suitable technique for screening new compound to determine cytotoxicity on cancer cells in short period of time. [ 20 ] The results from MTT assay indicated that crocin inhibited the growth of FTC‐133 cells in a dose‐dependent manner.…”