Apoptotic Effects of a Thioether Analog of Vitamin K3 in a Human Leukemia Cell Line

Research suggests that thioether analogs of vitamin K3 (VK3) can act to preserve the phosphorylation of epidermal growth factor receptors by blocking enzymes (phosphatases) responsible for their dephosphorylation. Additionally, these derivatives can induce apoptosis via mitogen-activated protein kinase and caspase-3 activation, inducing reactive oxygen species (ROS) production, and apoptosis. However, vitamin K1 exhibits only weak inhibition of phosphatase activity, while the ability of VK3 to cause oxidative DNA damage has raised concerns about carcinogenicity. Hence, in the current study, we designed, synthesized, and screened a number of VK3 analogs for their ability to enhance phosphorylation activity, without inducing off-target effects, such as DNA damage. 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) assay revealed that each analog produced a different level of cytotoxicity in the Jurkat human leukemia cell line; however, none elicited a cytotoxic effect that differed significantly from that of the control. Of the VK3 analogs, CPD5 exhibited the lowest EC50, and flow cytometry results showed that apoptosis was induced at final concentrations of ≥10 μM; hence, only 0.1, 1, and 10 μM were evaluated in subsequent assays. Furthermore, CPD5 did not cause vitamin K-attributed ROS generation and was found to be associated with a significant increase in caspase 3 expression, indicating that, of the synthesized thioether VK3 analogs, CPD5 was a more potent inducer of apoptosis than VK3. Hence, further elucidation of the apoptosis-inducing effect of CPD5 may reveal its efficacy in other neoplastic cells and its potential as a medication.

Evaluation of Anticancer Action of Martynia annua Linn Root Extract on Different Human Cancer Cell Lines

Background: In the last few decades, plants have been playing a vital role in treating cancer and infectious diseases. Natural products have been rediscovered as effective methods of drug production amid advances in combinatorial chemistry. Roots of Martynia annua are being used as a folklore remedy for the treatment of cancer and rheumatism successfully. Aims of the Study: In the present study, ethanolic, aqueous and hydro-ethanolic root extracts of Martynia annua were screened for in vitro cytotoxicity activity using different cell lines. Settings and Design: In the experiment, lung cancer cell lines (A549), leukemia cancer cell lines (K562), oral cancer cell lines (SCC-40), breast cancer cell lines (MCF-7) & cervix cancer cell lines (SiHa) were studied on the extracts. Materials and Methods: The method used was Sulforhodamine B (SRB) assay technique in which growth inhibition of 50% (GI50) was analyzed by comparing it with standard drug Adriamycin (ADR) (doxorubicin). Results: Aqueous & ethanolic extract of Martynia annua root had shown high anticancer activity with GI50 value 11.3µg/ml and 20.4µg/ml respectively on human leukemia cell line K-562 but for human breast cancer cell line MCF-7, human lung cancer cell line A-549, human squamous cell carcinoma SCC-40 and human cervical cancer cell line SiHa the extracts showed activity in more than 80µg/ml. Conclusion: The anticancer activity of aqueous extract of Martynia annua root was found superior than the ethanolic extract in Human Leukemia Cell Line K-562. The study indicates that the Martynia annua root extracts are most effective against the fast proliferative cells (Leukemic cells) and possibly a cell cycle arrest (needed to be proved as future perspective) is the mode of action of the extract. To study its effect on targeted cancers, specific in vivo scientific studies and clinical trials should be carried out by further researchers.

Chemotaxis and swarming in differentiated HL-60 neutrophil-like cells

The human leukemia cell line (HL-60) is an alternative to primary neutrophils in research studies. However, because HL-60 cells proliferate in an incompletely differentiated state, they must undergo differentiation before they acquire the functional properties of neutrophils. Here we provide evidence of swarming and chemotaxis in differentiated HL-60 neutrophil-like cells (dHL-60) using precise microfluidic assays. We found that dimethyl sulfoxide differentiated HL-60 cells (DdHL-60) have a larger size, increased length, and lower ability to squeeze through narrow channels compared to primary neutrophils. They migrate through tapered microfluidic channels slower than primary neutrophils, but faster than HL-60s differentiated by other protocols, e.g., using all-trans retinoic acid. We found that dHL-60 can swarm toward zymosan particle clusters, though they display disorganized migratory patterns and produce swarms of smaller size compared to primary neutrophils.

A novel translation inhibitor, mersicarpine, inhibits S-phase progression and induces apoptosis in HL60 cells

Mersicarpine is an aspidosperma alkaloid isolated from the Kopsia genus of plants. Its intriguing structural features have attracted much attention in synthetic organic chemistry, but no biological activity has been reported. Here, we report the effects of mersicarpine on human leukemia cell line HL60. At concentrations above 30 µm, mersicarpine reversibly arrested cell cycle progression in S-phase. At higher concentrations, it induced not only production of reactive oxygen species, but also apoptosis. Macromolecular synthesis assay revealed that mersicarpine specifically inhibits protein synthesis. These results suggest that mersicarpine is a novel translation inhibitor that induces apoptosis.

Chemotaxis and swarming in differentiated HL60 neutrophil-like cells

ABSTRACTHuman leukemia cell line (HL-60) is an alternative to primary neutrophils in research studies. However, because HL-60 cells proliferate in an incompletely differentiated state, they must undergo differentiation before they acquire the functional properties of neutrophils. Here we provide evidence of swarming and chemotaxis in HL-60 neutrophil-like cells using precision microfluidic assays. We found that dimethyl sulfoxide (DMSO) differentiated HL-60 cells have larger size, increased length, and lower ability to squeeze through narrow channels compared to primary neutrophils. They migrate through tapered microfluidic channels slower than primary neutrophils, but faster than HL60s differentiated by other protocols, e.g. using all-trans retinoic acid. We found that differentiated HL-60 can swarm toward zymosan particle clusters, though they display disorganized migratory patterns and produce swarms of smaller size compared to primary neutrophils.