Alantolactone, a sesquiterpene lactone, inhibits breast cancer growth by antiangiogenic activity via blocking VEGFR2 signaling

Liu, Yarong; Cai, Qinyi; Gao, Yun‐Jie; Luan, Xin; Guan, Yong-Song; Lü, Qing; Sun, Peng; Zhao, Mei; Fang, Chao

doi:10.1002/ptr.6004

Cited by 27 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was found that santonin exerts significant anticancer effects on the SK-BR-3 ovarian cancer cells by inhibiting the proliferation of the SK-BR-3 cancer cells concentration dependently. These observations confirmed previous investigations wherein sesquiterpene lactone was shown to halt the growth of the cancer cells; for example, alantolactone which is a plant derived sesquiterpene has been reported to suppress the growth of the breast cancer cells [16]. Similarly, calein C, which is another sesquiterpene lactone has been reported to suppress the growth of cancer cells [17].…”

Section: Discussionsupporting

confidence: 89%

Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway

Wang

Huang

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

Background Sesquiterpene lactones have gained tremendous attention owing to their potent anticancer properties. The main focus of this study was to evaluate the anticancer effects of a naturally occurring sesquiterpene lactone, santonin, against human breast cancer SK-BR-3 cells. Material/Methods Cell counting kit 8 assay was used for the determination of cell viability. Apoptosis was detected by DAPI (4′,6-diamidino-2-phenylindole) and annexin V/propidium iodide (IP) staining. Flow cytometry was used for cell cycle analysis and western blotting was used for the estimation of protein expression. Results Results showed that santonin exerts significant anti-proliferative effects on the SK-BR-3 breast cancer cells in a concentration dependent manner. Santonin showed an IC 50 of 16 μM against SK-BR-3 cells. DAPI staining showed that santonin caused DNA fragmentation in the SK-BR-3 cells, which is indicative of apoptosis. Annexin V/PI staining showed that apoptotic cell percentage increased up to 34.32% at 32 μM concentration of santonin. Santonin also caused an increase in the expression of Bax, caspase-3, and caspase-9, and a decrease in the expression of Bcl-2. Santonin also caused the arrest of the SK-BR-3 cells at the G2/M phase of the cell cycle and suppressed the expression of cyclin A and B1. Finally, santonin could also block the Raf/MEK/ERK pathway in breast cancer cells. Conclusions The findings of this study suggest the potential for the naturally occurring sesquiterpene lactone santonin in breast cancer treatment and also suggest that it could be developed as a promising anticancer agent.

show abstract

Section: Discussionsupporting

confidence: 89%

Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway

Wang

Huang

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…As a critical component of tumor angiogenesis, glycoprotein vascular endothelial growth factor (VEGF) is widely expressed in many cancers [100,101], while the vascular endothelial growth factors receptor-2 (VEGFR2) increased signaling is also characteristic of angiogenesis in tumors [102,103,104]. Alantolactone ( 11 ) (Figure 2) exhibits anti-angiogenesis property, since it shows anti-proliferative activity against human umbilical vascular endothelial cells (HUVEC) (IC 50 = 14.2 μM), a model cell line used to study angiogenesis processes [105]. The alantolactone ( 11 ) anti-angiogenesis property could be related with its capacity to decrease capillary formation, by suppressing VEGFR2 signaling and decreasing the expression of its multiple downstream protein kinases, e.g., focal adhesion kinase (FAK) [105].…”

Section: Secondary Metabolites From Inula Species Against Oxidativmentioning

confidence: 99%

Inula L. Secondary Metabolites against Oxidative Stress-Related Human Diseases

Tavares

Seca

2019

Antioxidants

View full text Add to dashboard Cite

An imbalance in the production of reactive oxygen species in the body can cause an increase of oxidative stress that leads to oxidative damage to cells and tissues, which culminates in the development or aggravation of some chronic diseases, such as inflammation, diabetes mellitus, cancer, cardiovascular disease, and obesity. Secondary metabolites from Inula species can play an important role in the prevention and treatment of the oxidative stress-related diseases mentioned above. The databases Scopus, PubMed, and Web of Science and the combining terms Inula, antioxidant and secondary metabolites were used in the research for this review. More than 120 articles are reviewed, highlighting the most active compounds with special emphasis on the elucidation of their antioxidative-stress mechanism of action, which increases the knowledge about their potential in the fight against inflammation, cancer, neurodegeneration, and diabetes. Alantolactone is the most polyvalent compound, reporting interesting EC50 values for several bioactivities, while 1-O-acetylbritannilactone can be pointed out as a promising lead compound for the development of analogues with interesting properties. The Inula genus is a good bet as source of structurally diverse compounds with antioxidant activity that can act via different mechanisms to fight several oxidative stress-related human diseases, being useful for development of new drugs.

show abstract

“…Notably, ALT was suggested to exhibit potential anti-cancer activity against various types of cancer, including human colorectal cancer (10), liver cancer (11,12), leukemia (13), breast cancer (14), lung cancer (15,16) and cervical cancer (17,18). ALT may inhibit breast cancer growth via anti-angiogenic activity by inhibiting vascular endothelial growth factor receptor 2 and RAC-alpha serine/threonine-protein kinase B (AKT) signaling (19). In human cervical cancer cells, ALT induces apoptosis via generation of reactive oxygen species (ROS) and inhibition of the B-cell lymphoma 2 (Bcl-2)/Bcl-2 associated X apoptosis regulator (Bax) signaling pathway (17).…”

Section: Introductionmentioning

confidence: 99%

Alantolactone induces gastric cancer BGC‑823 cell apoptosis by regulating reactive oxygen species generation and the AKT signaling pathway

Zhang

2019

Oncol Lett

View full text Add to dashboard Cite

Alantolactone (ALT), a natural sesquiterpene lactone, has been suggested to exert anti-cancer activities in various cancer cell lines. However, the effects and mechanisms of action of ALT in human gastric cancer remains to be elucidated. In the present study, the effects of ALT on BGC-823 cells were examined and the underlying molecular mechanisms associated with these effects were investigated. Cell viability was detected by using an MTT assay. Cell cycle, cell apoptosis and the level of reactive oxygen species (ROS) were assessed by flow cytometry, and the expression levels of proteins of interest were analyzed by western blot assay. The results demonstrated that ALT triggered apoptosis and induced G0/G1 phase arrest in a dose-dependent manner. Furthermore, the expression level of the anti-apoptosis protein Bcl-2 was downregulated, and expression of the pro-apoptosis proteins Bax and cleaved PARP were significantly upregulated. The cell cycle-associated proteins cyclin-dependent kinase inhibitor 1 and cyclin-dependent kinase inhibitor 1B were also increased, while cyclin D1 was deceased. In addition, ALT induced apoptosis via the inhibition of RAC-alpha serine/threonine-protein kinase (AKT) signaling and ROS generation, which was effectively inhibited by the ROS scavenger, N-acetyl cysteine. Therefore, the results from the present study indicated that the ROS-mediated inhibition of the AKT signaling pathway serves an important role in ALT-induced apoptosis in BGC-823 cells. In conclusion, the results demonstrated that ALT exerted significant anti-cancer effects against gastric cancer cells in vitro .

show abstract

Alantolactone, a sesquiterpene lactone, inhibits breast cancer growth by antiangiogenic activity via blocking VEGFR2 signaling

Cited by 27 publications

References 26 publications

Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway

Naturally Occurring Sesquiterpene Lactone-Santonin, Exerts Anticancer Effects in Multi-Drug Resistant Breast Cancer Cells by Inducing Mitochondrial Mediated Apoptosis, Caspase Activation, Cell Cycle Arrest, and by Targeting Ras/Raf/MEK/ERK Signaling Pathway

Inula L. Secondary Metabolites against Oxidative Stress-Related Human Diseases

Alantolactone induces gastric cancer BGC‑823 cell apoptosis by regulating reactive oxygen species generation and the AKT signaling pathway

Contact Info

Product

Resources

About