Abstract
BackgroundPiperlongumine (PL) is a compound isolated from the piper longum plant. It possesses anti-cancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It also inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known.ObjectiveWe conducted in vitro experiments to test the hypothesis that PL regulates a non-transcriptional activity of STAT3 to specifically reduce the reactivity of human platelets to collagen.ResultsPL dose-dependently blocked collagen-induced platelet aggregation, calcium influx, CD62p expression and thrombus formation on collagen with a maximal inhibition at 100 μM. It reduced platelet microvesiculation induced by collagen. PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets. This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor. Although PL induced ROS production in platelets; quenching ROS using excessive reducing agents: 20 μM GSH and 0.5 mM L-Cysteine, did not block the inhibitory effects. The NADPH oxidase inhibitor Apocynin also had no effect.ConclusionsPL inhibited collagen-induced platelet reactivity by targeting the JAK2-STAT3 pathway. We also provide experimental evidence that PL and collagen induce different oxidants that have differential effects on platelets. Studying these differential effects may uncover new mechanisms of regulating platelet functions by oxidants in redox signals.
Highlights
The long pepper (Piper longum) is a member of the Piper genus known to possess anti-allergenic, anti-inflammatory, and liver protecting properties [1;2]
PL blocked the activation of JAK2 and STAT3 in collagen-stimulated platelets
This inhibitory effect was significantly reduced in platelets pretreated with a STAT3 inhibitor
Summary
The long pepper (Piper longum) is a member of the Piper genus known to possess anti-allergenic, anti-inflammatory, and liver protecting properties [1;2]. Raj L, et al [11] reported that PL selectively induces the death of cancer or transformed cells, while preserving the viability of normal cells in vitro and in vivo This targeted activity relies on PL’s ability to increase intracellular reactive oxygen species (ROS), especially hydrogen peroxide and nitric oxide [11]. Piperlongumine (PL) is a compound isolated from the piper longum plant It possesses anticancer activities through blocking the transcription factor STAT3 and by inducing reactive oxygen species (ROS) in cancer, but not normal cells. It inhibits platelet aggregation induced by collagen, but the underlying mechanism is not known
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