Licochalcone A inhibits PI3K/Akt/mTOR signaling pathway activation and promotes autophagy in breast cancer cells

Abstract

Abstract. Previous studies have demonstrated that LicochalconeA possesses anti-inflammatory, anticancer, anti-bacterial, anti-malarial and anti-parasitic activities. In the present study the potential anticancer effects of Licochalcone A on MCF-7 cells were investigated. Licochalcone A significantly decreased cell viability and promoted autophagy and apoptosis, as demonstrated by an MTT assay, acridine orange staining and Annexin V-fluorescein isothiocyanate staining, respectively. Western blot analyses demonstrated that Licochalcone A treatment activated the LC3-II signaling pathway while suppressing the phosphoinositide 3-kinase (PI3K)/RAC-α serine-threonine-protein kinase (Akt)/mammalian target of rapamycin (mTOR) signaling pathway. In addition, Licochalcone A significantly increased caspase-3 activity and significantly decreased B-cell lymphoma-2 expression. The results from the present study indicate that Licochalcone A inhibits PI3K/Akt/mTOR activation, and promotes autophagy and apoptosis in MCF-7 cells.

Lanatoside C Induces G2/M Cell Cycle Arrest and Suppresses Cancer Cell Growth by Attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR Signaling Pathways

“…Thus, activation of the PI3K/AKT/mTOR pathway plays a vital role in cancer disease progression, protein synthesis, and is recognized as one of the key targets for novel treatment approaches [64,65]. Inhibitors of the PI3K/AKT/mTOR pathway have been recognized as novel drugs for anticancer therapy [66]. Inhibitors of mTOR and PI3K through various stress conditions by chemotherapeutic drugs lead to the activation of AKT, which directly inhibits mTOR through several regulators.…”

Natural Chalcones in Chinese Materia Medica: Licorice

“…Licochalcone A induced apoptosis of gastric cancer cells via the caspase-dependent mitochondrial pathway and exerted G2 cell cycle arrest through the regulation of G2/M phase checkpoint proteins [40]. Additionally, it handled activation of the LC3-II signaling pathway while inhibiting the phosphatidylinositol 3kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) signaling pathway that promoted autophagy and apoptosis in cells [41]. Licochalcone A caused G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells by affecting the expression of proliferating cell nuclear antigen (PCNA), DNA polymerase δ, Rb and E2F, cyclins B1 and D1, and so on, which led to apoptosis [42].…”

CUL4B regulates autophagy via JNK signaling in diffuse large B-cell lymphoma

“…To unravel the mechanisms of CUL4B regulating autophagy in DLBCL cells, possible regulatory pathways were evaluated. Several signaling pathways have been demonstrated to participate in autophagy regulation in solid cancers [25][26][27][28], but the mediated mechanisms in DLBCL still remains unknown. Previous research regarded the regulating pathways, mainly PI3K/AKT/mTOR and JNK signaling pathways, as the targeted treatment for DLBCL due to their positive regulation in further promotion of cell survival, proliferation, and drug resistance [2,29,30].…”