Aloperine inhibits proliferation, migration and invasion and induces apoptosis by blocking the Ras signaling pathway in human breast cancer cells

Abstract

Aloperine (Alo), as a quinolizidine alkaloid extracted from S. alopecuroide, has the positive activities of anti-inflammatory, anti-allergenic, antitumor and anti-viral. However, the role and mechanism of Alo in breast cancer have not been studied yet. In the present study, Alo markedly inhibited the proliferation and suppressed the colony formation ability of the breast cancer cell lines MCF-7 and MDA-MB-231 in a dose-dependent manner by Cell Counting kit-8 and colony formation assays, respectively. In addition, the results of confocal microscopy analysis and flow cytometry detection revealed that Alo induced the apoptosis of MCF-7 and MDA-MB-231 cells, and western blotting indicated that Alo upregulated the protein levels of Bax, caspase-3 and caspase-9, and downregulated the expression of Bcl-2. Furthermore, the results of wound healing, Transwell migration and invasion assays demonstrated that Alo inhibited the migration and invasion of MCF-7 and MDA-MB-231 cells, and reduced the protein levels of matrix metalloproteinase (MMP)-2 and MMP-9. Alo also downregulated the protein expressions of Ras, phosphorylated (p)-Raf proto-oncogene, serine/threonine kinase 1 and p-extracellular signal-regulated kinase 1/2. Furthermore, ISIS 2503, a Ras inhibitor, inhibited colony formation, induced apoptosis, and suppressed the migration and invasion of MCF-7 and MDA-MB-231 cells. These effects were more marked in the presence of ISIS 2503 and Alo, when compared with those of either agent alone. In conclusion, the present study reported a novel use of Alo in inhibiting the proliferation, migration and invasion, and inducing the apoptosis of human breast cancer cells by blocking the Ras signaling pathway.

The Effects of Trifolium pratense L. Sprouts’ Phenolic Compounds on Cell Growth and Migration of MDA-MB-231, MCF-7 and HUVEC Cells

“…Studies performed with PC-3 cells revealed that ERβ-selective agonist DPN decreased the expression of N-cadherin [52] which is consistent with what was observed by us-downregulation of N-cadherin in the presence of isoflavones. Because ERβ activation was also related with the induction of apoptosis in PC-3M cells, apoptotic cell death may result not only from cytotoxic activity of extract components, but also could be used as functional link for agonistic aglycons binding to ERβ protein [53]. On the other hand, studies performed on the submandibular gland of the rat (an extensive postnatal development model) revealed that by biochanin A was involved in ERβ expression up-regulation [54].…”

Aloperine prevents hypoxia-induced epithelial-mesenchymal transition in bladder cancer cells through regulating the mTOR/p70S6K/4E-BP1 pathway

“…For instance, ALO exhibits anti-tumor activity on human thyroid cancer, as proven by its inhibitory effects on cell growth in human anaplastic thyroid cancers and multidrug-resistant papillary thyroid cancers [16]. ALO inhibits proliferation, migration and invasion and induces apoptosis in human breast cancer cells [24]. ALO executes anti-tumor effects on prostate cancer through the induction of apoptosis and cell cycle arrest both in vitro and in vivo [15].…”

Research Progress on Anti‐Inflammatory Effects and Mechanisms of Alkaloids from Chinese Medical Herbs

“…In terms of respiratory diseases, intragastric administration of 40 mg/kg of aloperine can improve lung function, alleviate asthma symptoms, and inhibit inflammatory responses in asthmatic mice. e mechanism is related to the regulation of the NF-κB inflammatory signal pathway and the reduction of TNF-α and IL-1β levels [51].…”