Alantolactone induces apoptosis and suppresses migration in MCF‑7 human breast cancer cells via the p38�MAPK, NF‑κB and Nrf2 signaling pathways

Abstract

Human breast cancer is a malignant type of cancer with high prevalence. In the present study, the anticancer effects of alantolactone, a sesquiterpene lactone, on the human breast cancer cell line MF-7 were investigated in vitro. The MCF-7 cell morphology changed from diamond to round subsequent to treatment with alantolactone, and the cell viability reduced significantly compared with that of the control cells. Alantolactone induced apoptosis of MCF-7 cells by regulating the protein expression levels of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, p53, caspase-3 and caspase-12, which are associated with the apoptotic pathway, and suppressed colony formation and migration by regulating the protein expression of matrix metalloproteinase (MMP)-2, MMP-7 and MMP-9. Cell signaling pathway analysis confirmed that alantolactone increased the phosphorylation of p38, and decreased the nuclear expression levels of p65 and nuclear factor erythroid 2-related factor 2 (Nrf2), suggesting that the apoptosis-promoting and migration-suppressing effect of alantolactone may partially depend on regulating the p38 MAPK, NF-κB and Nrf2 pathways. These results also suggested that alantolactone may become a potential therapeutic strategy for treating breast cancer.

Synergistic lethality between PARP-trapping and alantolactone-induced oxidative DNA damage in homologous recombination-proficient cancer cells

“…Tumor cell toxicity is a well-known property of ATL, but the effective concentrations reported in the literature were very high, with IC 50 values ranging from 20 to 60 μM in various solid tumor cell lines [38][39][40]. In agreement with the literature, we found 10 μM ATL had no significant impact on the clonogenic growth of many human cancer cell lines ( Fig.…”

Anti-Neuroinflammatory Effect of Alantolactone through the Suppression of the NF-κB and MAPK Signaling Pathways

“…Ala has been reported to exhibit significant anticancer effects by modulating the activity of the NF-κB and MAPK signaling pathways [26,27]. To our surprised, NF-κB and MAPK signaling pathways are also the major mechanisms of injurious neuroinflammation by upregulating the expression expression of proinflammatory factors to cause cell apoptosis or necrosis.…”

“…Surprisingly, alantolactone (Ala), a sesquiterpene lactone isolated from Inula helenium, has been proven to be able to have an inhibitory effect on the growth of tumors by causing the significantly downregulated expression of proinflammatory factors [23][24][25]. Moreover, Ala induces apoptosis and suppresses the migration of MCF-7 human breast cancer cells by targeting the MAPK and NF-κB signaling pathways [26]. Thus, it is reasonable to propose that Ala might be a potential anti-neuroinflammatory agent for CNS injury therapy.…”

Alantolactone suppresses human osteosarcoma through the PI3K/AKT signaling pathway

“…Previous studies have reported that alT promotes numerous biological effects, including anti-inflammatory and antioxidant functions (18,19). it has also been observed to suppress several types of human cancer, including gastric, pancreatic and breast cancer cells (19)(20)(21). it is reported that these anticancer effects of alT are mediated through the Pi3K/aKT signaling pathway (22).…”