Convallatoxin, the primary cardiac glycoside in lily of the valley (Convallaria majalis), induces tissue factor expression in endothelial cells

Abstract

Background: Convallotoxin (CNT), present in lily of the valley (Convallaria majalis), is a toxin that causes food poisoning among humans and companion animals. Although various symptoms of CNT poisoning have been well described, hypercoagulability owing to CNT is only empirically known among some veterinarians, and the underlying mechanism remains to be elucidated. CNT exerts cytotoxic effects on endothelial cells.Objectives: This study aimed to determine whether CNT induces the expression of tissue factor (TF), a potent initiator of the extrinsic coagulation cascade, in endothelial cells and leads to a hypercoagulable state.Methods: Human umbilical vein endothelial cells (HUVECs) were used for in vitro experiments. HUVECs were treated with or without CNT (50 and 100 nM) for 4 h. Phosphate-buffered saline was used as a control. Cell viability was determined using the WST-8 assay. Quantitative real-time polymerase chain reaction was performed to determine TF mRNA expression. TF protein expression was observed using a laser scanning confocal microscope. Results:The viability of HUVECs significantly reduced after CNT treatment compared with that of non-treated cells (p < 0.05). Moreover, a significant increase in TF mRNA and protein expression was observed after 4 h of CNT treatment. CNT elicited these effects in a dose-dependent manner.Conclusions: TF expression induced by CNT in endothelial cells can contribute to the development of a hypercoagulable state. The present study partially revealed the mechanisms underlying the CNT-induced hypercoagulable state. The findings can contribute to the development of a novel therapy for lily of the valley poisoning.

Involvement of monocyte-derived extracellular vesicle-associated tissue factor activity in convallatoxin-induced hypercoagulability

“…The findings of the present study together with our previous findings indicate that CNT treatment increases TF expression in vascular endothelial cells [4] and establish the procoagulant properties of CNT. Virchow's triad describes three factors that contribute to thrombosis: endothelial damage, stasis of blood flow, and hypercoagulability [21].…”

“…In previous studies, we detected CNT-induced tissue factor (TF) expression in endothelial cells, and found that this endothelial cell-derived TF may trigger a hypercoagulable state in CNT poisoning [4]. However, the mechanism of direct action of CNT on blood components remains unclear.…”

Advances in Osteosarcoma

“…Cardiac glycoside has been reported as a potent anti-tumor molecule as it selectively inhibits tumor cell proliferation [ 41 ]. Convallatoxin is a natural cardiac glycoside found in Convallaria majalis , a plant known as Lily of the valley [ 44 ]. It has been reported that convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis in colorectal cancer cells [ 45 ].…”

Convallatoxin suppresses osteosarcoma cell proliferation, migration, invasion, and enhances osteogenic differentiation by downregulating parathyroid hormone receptor 1 (PTHR1) expression and inactivating Wnt/β-catenin pathway

“…Cardiac glycoside, a class of steroidal glycosides with significant physiological activities, has been reported to possess potent antitumor efficacy and to selectively inhibit the proliferation of human tumor cells [ 6 , 7 ]. Convallatoxin, which can be found in lily of the valley (Convallaria majalis), is a natural cardiac glycoside [ 8 ]. Research has testified that convallatoxin exhibits obvious anti-tumor potential.…”