Anticancer Potential of Aguerin B, a Sesquiterpene Lactone Isolated from Centaurea behen in Metastatic Breast Cancer Cells

Abstract

Background: Breast carcinoma is a malignant disease that represents the most common non-skin malignancy and a chief reason of cancer death in women. Large interest is growing in the use of natural products for cancer treatment, especially with goal of suppression angiogenesis, tumor cell growth, motility, as well as invasion and metastasis with low/no toxicity. It is evident from recent patents on the anticancer properties of sesquiterpene lactones such as parthenolide. Objective: In this study, using MDA-MB-231 cells of a human breast adenocarcinoma, the effects of aguerin B, as a natural sesquiterpene lactone, has been evaluated, in terms of the expression of metastatic-related genes (Pak-1, Rac-1 and HIF-1α). Methods: Cytotoxicity of aguerin B was tested toward MDA-MB-231 breast tumor cells using MTT. Scratch assay was accomplished to evaluate the tumor cell invasion. To understand the underlying molecular basis, the mRNA expressions were evaluated by real time PCR. Results: It was found that aguerin B significantly inhibited human breast cancer cell growth in vitro (IC50 = 2µg/mL) and this effect was accompanied with a persuasive suppression on metastasis. Our results showed that aguerin B in IC50 concentration down-regulated Rac-1, Pak-1, Hif-1α and Zeb-1 transcriptional levels. Conclusion: Taken together, this study demonstrated that aguerin B possessed potential anti-metastatic effect, suggesting that it may consider as a potential multi target bio compound for treatment of breast metastatic carcinoma.

Sesquiterpene Lactones as Promising Candidates for Cancer Therapy: Focus on Pancreatic Cancer

“…Of the two compounds, only aguerin B was demonstrated to induce apoptotic cell death, ratifying the role as pro-apoptotic moiety of the α-methylene-γ-lactone ring present in aguerin B but not in the newly identified 15-nor-guaianolide [ 113 ]. Moreover, aguerin B showed a better anti-proliferative effect than 5-fluorouracil (5-FU), another drug commonly used as first line in pancreatic anticancer therapy [ 114 ]. The IC 50 values obtained for aguerin B were significantly lower in comparison to those obtained with 5-FU, showing a greater amount (more than twice) of apoptotic cells compared with vehicle-treated cells [ 113 ].…”

“…The IC 50 values obtained for aguerin B were significantly lower in comparison to those obtained with 5-FU, showing a greater amount (more than twice) of apoptotic cells compared with vehicle-treated cells [ 113 ]. Although the mechanism by which aguerin B exerts antitumor effect in pancreatic cancer has not been studied, it has been described that this compound significantly inhibited human breast cancer cell growth in vitro with a persuasive suppression on metastasis via downregulation of Hif-1α, among others [ 114 ]. Yokoi et al (2004) published that at low O 2 levels, resistance to gemcitabine was exerted mainly via activation of phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) and nuclear-factor-kappa-light-chain enhancer of activated B-cells (NF-κB) signaling pathways and partially through the MAPK(Erk) signaling pathway [ 115 ].…”