Abstract
Cervical cancer as one of the major malignant tumors seriously threatens women's health. More than 270,000 women die of cervical cancer each year. Warangalone is an isoflavone compound isolated from Cudrania tricuspidata with excellent antitumor activity. In this research, we investigated the molecular mechanism of warangalone‐induced apoptosis in HeLa cells. The results show that warangalone can selectively and effectively inhibit HeLa cells proliferation. Warangalone can effectively inhibit the invasion and migration of HeLa cells. Furthermore, warangalone was confirmed to activate p53 and mitogen‐activated protein kinase (MAPK) family signaling pathways to cause apoptosis. In this case, the expression of the B‐cell lymphoma‐2 (Bcl‐2) family is regulated, and caspase‐3 is eventually cleaved, finally triggering the mitochondrial apoptosis. In conclusion, warangalone can induce HeLa cells apoptosis via a mitochondria‐mediated endogenous pathway, which represented the potential therapeutic effect of warangalone on cervical cancer.
Highlights
Cervical cancer as one of the major malignant tumors seriously threatens women’s health
The results showed that treatment of cells with warangalone destroyed the membrane potential of mitochondria and decreased the mitochondrial membrane potential of HeLa cells in a dosedependent manner, which indicated that mitochondria were involved in the process of warangalone-induced apoptosis of HeLa cells
Warangalone causes the activation of p53 and mitogen-activated protein kinase (MAPK) family signaling pathways by promoting the phosphorylation of p38 and inhibiting the phosphorylation of extracellular regulated protein kinases (ERK), regulating B-cell lymphoma-2 (Bcl-2) family expression and triggering the apoptosis of HeLa cells
Summary
Cervical cancer as one of the major malignant tumors seriously threatens women’s health. Warangalone is an isoflavone compound isolated from Cudrania tricuspidata with excellent antitumor activity. Warangalone was confirmed to activate p53 and mitogen-activated protein kinase (MAPK) family signaling pathways to cause apoptosis. Warangalone can induce HeLa cells apoptosis via a mitochondria-mediated endogenous pathway, which represented the potential therapeutic effect of warangalone on cervical cancer. The research on isoflavones anti-cervical cancer signaling pathways mainly focuses on the apoptosis signaling pathway, extracellular regulated protein kinases (ERK) / MAPK and PI3K / Akt signaling pathway [16, 17]. Warangalone isolated and purified from the fruits of Cudrania Tricuspidata is an isoflavone compound with antitumor biological activities [23]. Based on the advantages of warangalone with low toxicity and good antitumor activity, it is interesting to explore the specific mechanism of warangalone against cervical tumors
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