ABSTRACT
Considering the high morbidity and mortality rates associated with hematological malignancies and the frequent development of drug resistance by these diseases, the search for new cytotoxic agents is an urgent necessity. The new compounds should present higher efficiency and specificity in inducing tumor cell death, be easily administered and have little or negligible adverse effects. Quinones have been reported in the literature by their several pharmacological properties, including antitumor activity, thus, the aim of this study was to investigate the cytotoxic effect of primin, a natural quinone, on hematological malignancies cell lines. Primin was highly cytotoxic against the three cell lines included in this study (K562, Jurkat and MM.1S) in a concentration- and time-dependent manner, as demonstrated by the MTT method. The compound triggered an apoptotic-like cell death, as observed by ethidium bromide/acridine orange staining, DNA fragmentation and phosphatidylserine exposure after labeling with Annexin V. Both intrinsic and extrinsic apoptosis are involved in cell death induced by primin, as well as the modulation of cell proliferation marker KI-67. The activation of intrinsic apoptosis appears to be related to a decreased Bcl-2 expression and increased Bax expression. While the increase in FasR expression signals activate extrinsic apoptosis. The results suggest that primin is a promising natural molecule that could be used in hematological malignancies therapy or as prototypes for the development of new chemotherapics.
Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzoquinones/pharmacology , Hematologic Neoplasms/drug therapy , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Agents, Phytogenic/isolation & purification , Apoptosis/drug effects , Apoptosis Inducing Factor/metabolism , Benzoquinones/adverse effects , Benzoquinones/isolation & purification , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Eugenia/chemistry , Hematologic Neoplasms/metabolism , Hematologic Neoplasms/pathology , Humans , Jurkat Cells , K562 Cells , Plant Extracts/isolation & purification , Plant Extracts/pharmacology , Proto-Oncogene Proteins c-bcl-2/metabolism , bcl-2-Associated X Protein/metabolismABSTRACT
Molecular networking (MN) can efficiently dereplicate extracts and pure compounds. Red algae of the genus Laurencia are rich in halogenated secondary metabolites, mainly sesquiterpenes and C15-acetogenins. Brown algae of the genus Dictyopteris produce mainly C11-hydrocarbons, sesquiterpenes and sulfur-containing compounds, while Dictyota and Canistrocarpus are reported to contain mainly diterpenes. This study performs an exploratory MN analysis of 14 extracts from algae collected in Brazil (including the oceanic islands) and characterizes the secondary metabolites from the analyzed species. The extracts and some isolated metabolites were analyzed by LC-MS using the FastDDA algorithm, and the MS/MS spectra were submitted to GNPS and displayed in Cytoscape 3.5.1. The GNPS platform generated 68 individual nodes and nine family networks. The MN exploratory analysis indicated chemical differences among species, and also in sampling sites for the same species. For some extracts, it was possible to identify mass values that could correspond to terpenoids and C15-acetogenins that have already been isolated from those or related species. An interesting chemodiversity was highlighted between Laurencia catarinensis from two nearby islands, and this was revealed and was also suggested by the family networks. Many nodes in the MN could not be characterized, and these metabolites can be used as targets for isolation in future works.
