Centipedegrass extract induces apoptosis through the activation of caspases and the downregulation of PI3K/AKT and MAPK phosphorylation in leukemia cells

Abstract

Acute lymphoblastic leukemia (ALL), which involves the blood and bone marrow, is the most common type of cancer in children younger than 5 years of age. Previous studies have investigated the effects of centipedegrass extract (CGE), which is mainly composed of maysin and its derivatives, and have demonstrated that it has various biological activities, including antioxidant and anti‑inflammatory activities, pancreatic lipase inhibitory activity, anti-adipogenic activity and insecticidal activity. To the best of our knowledge, this study is the first to investigate the anticancer effects of CGE in ALL cell lines and to elucidate the mechanisms underlying these effects. Cell viability was measured by thiazolyl blue tetrazolium blue (MTT) assay. Apoptosis, cell cycle progression and mitochondrial membrane potential (∆Ψm) were determined by flow cytometry. The effects of CGE on the phosphatidylinositol 3‑kinase (PI3K)/Akt pathway and mitogen‑activated protein kinases (MAPKs) were assessed by immunoblotting. PI3K, MAPK and caspase inhibitors were used to further confirm the molecular mechanisms involved. Our results clearly demonstrated that the proliferation of the ALL cells was significantly inhibited by CGE in a dose‑dependent manner. Apoptosis was accompanied by the induction of significant G1 cell cycle arrest. The resulting alteration of the ∆Ψm increased the activity of caspase‑3/7. The induction of apoptosis was enhanced by the combined treatment of CGE with a PI3K inhibitor or an extracellular signal-regulated kinase (ERK) inhibitor, whereas the CGE‑induced apoptosis was inhibited in the presence of caspase inhibitors, such as z‑VAD‑fmk and z‑IETD‑fmk. Furthermore, CGE inhibited PI3K activity by decreasing the levels of phosphorylated (p‑)Akt, p‑BAD, and Bcl‑2 together with the levels of MAPKs, including p‑ERK and p‑JNK, but demonstrated no effects on p38 MAPK. Thus, our data suggest that CGE may be a novel natural compound with potential for use as an antitumor agent in ALL.

Boehmenan, a Lignan From the Chinese Medicinal Plant Clematis armandii, Inhibits A431 Cell Growth via Blocking p70S6/S6 Kinase Pathway

“…Furthermore, we also examined the effects of boehmenan on Akt/70S6 pathway activation, which is an important oncogenic signaling pathway involving growth and migration of cancer cells. 20 As shown in Figure5A to C , Western blot results revealed that boehmenan concentration-dependently inhibited EGF-induced 70S6 and S6 phosphorylation, but did not affect the Akt phosphorylation.…”

Thymus hirtus sp. algeriensis Boiss. and Reut. volatile oil enhances TRAIL/Apo2L induced apoptosis and inhibits colon carcinogenesis through upregulation of death receptor pathway

“…It has been shown that thyme essential oil significantly regulates interferon signaling, N-glycan biosynthesis and ERK5 signaling [ 26 ]. Therefore, it has been thought that activated AKT and ERK can function as key effectors of the PI3K and MAPK signaling pathways to promote cell survival and proliferation [ 32 ]. ERK1/2 has previously been evidenced to be able of inhibiting the apoptosis effector molecule caspase-3 [ 33 ].…”

Anti-proliferative effect of Jesridonin on paclitaxel-resistant EC109 human esophageal carcinoma cells

“…Apoptosis deficiency may be involved in cancer initiation, progression and treatment failure in cancers with MDR (19). Apoptosis is regulated at multiple levels in the extrinsic and intrinsic pathways (20). The extrinsic pathway involves death receptors on the cell surface that can directly activate caspase-8.…”