Jolkinolide A and Jolkinolide B Inhibit Proliferation of A549 Cells and Activity of Human Umbilical Vein Endothelial Cells

Abstract

BackgroundJolkinolide A (JA) and Jolkinolide B (JB) are diterpenoids extracted from the roots of Euphorbia fischeriana Steud and have been shown to have anti-tumor activity. However, their effects on the ability of tumor cells to invade blood vessels and metastasize remain largely unknown. Investigations into the effects of JA and JB on the angiogenesis of tumor tissues may facilitate the identification of new natural drugs with anti-tumor growth and metastasis activities.Material/MethodsWe used different concentrations of JA and JB (20 μg/ml, 40 μg/ml, 60 μg/ml, 80 μg/ml, and 100 μg/ml) to stimulate A549 cells and then studied the effects on the growth and metastasis of lung cancers. In addition, we used conditional media from A549 cells (A549-CM) stimulated by either JA or JB in different concentrations to culture human umbilical vein endothelial cells (HUVECs).ResultsWe found that both JA and JB significantly inhibited the Akt-STAT3-mTOR signaling pathway and reduced the expression of VEGF in A549 cells, but JB exhibited more significant inhibitory effects than JA. The JB-stimulated A549 cell conditional media had a greater inhibitory effect on the proliferation and migration of HUVECs than did the conditional media of JA-stimulated A549 cells. This effect gradually increased with increasing concentrations of either type of Jolkinolide.ConclusionsOur results suggest that JA and JB inhibited VEGF expression in A549 cells through the inhibition of the Akt-STAT3-mTOR signaling pathway, and directly inhibited the proliferation and migration of HUVECs. These findings are of great significance for the development of new plant-derived chemotherapy agents for the treatment of cancer.

WITHDRAWN: The Molecular Mechanism of ESZM Extract on Treatment ER(-) Breast Cancer in Vivo: Application of “Combat Poison with Poison” Theory

“…Jokinolide B has been shown to have de nite anti-tumor activity [19][20][21][22]. It has extracted several monomeric components from E. scheriana, such as Jolkinolide A [23], 17-acetoxyjolkinolide B [24], 17-hydroxyjolkinolide B [25], 12-Deoxyphorbol-13-palmitate [18, 26-27], and Jokinolide B, and proved to have signi cant anti-tumor activity from different directions. Therefore, in our study, herbal medicinal compound prescribe were selected as research object re ects the scienti c connotation of Chinese herbal with multiple components, multiple effects and multiple targets.…”

Jolkinolide B inhibits glycolysis by downregulating hexokinase 2 expression through inactivating the Akt/mTOR pathway in non‐small cell lung cancer cells

“…It has been proved that the Akt/mTOR signaling pathway is a crucial regulator of glycometabolic homeostasis . Published articles reported that JB reduced the expression of vascular endothelial growth factor (VEGF) which is important for tumor growth . The expression levels of Akt, STAT3, and mTOR proteins were also inhibited by JB in A549 cells, indicating that JB suppressed VEGF expression via inhibiting the Akt‐STAT3‐mTOR pathway .…”

“…For instance, JB was demonstrated to possess anti‐metastatic effect on breast cancer cells via inhibiting MAPK/ERK pathway . JB also inhibited the growth and metastasis of lung cancer through inhibiting the Akt/STAT3/mTOR signaling pathway . Moreover, JB was reported to induce apoptosis and inhibit tumor growth in mouse melanoma B16F10 cells by altering glycolysis .…”

Natural Products with Activity against Lung Cancer: A Review Focusing on the Tumor Microenvironment

“…The inhibitory effect of jolkinolide B is more obvious than that of jolkinolide A. The medium of A549 cells stimulated with either jolkinolide A or jolkinolide B was found to inhibit the proliferation and migration of human umbilical vein endothelial cells (HUVECs) in a concentration dependent manner [ 10 ]. Parthenolide ( 3 ), a sesquiterpene lactone extracted from Tanacetum parthenium , was shown to inhibit the proliferation of A549 cells in the absence and presence of nicotine.…”