UNBS5162 inhibits the proliferation of human A549 non‐small‐cell lung cancer cells by promoting apoptosis

Abstract

BackgroundLung cancer is one of the most frequently diagnosed malignancies in the world, thus developing novel anticancer reagents for lung cancer treatment is critical.MethodsWe performed cell counting kit‐8 and cell colony formation assays to investigate the role of UNBS5162 in the proliferation of A549 cells. Invasion and migration assays were applied to study the inhibitory effect of UNBS5162 on non‐small cell lung cancer cells. To detect the effect of UNBS5162 on A549 cell apoptosis, Annexin‐V fluorescein isothiocyanate and propidium iodide staining methods were used. Protein expression was analyzed using Western blot assay.Results UNBS5162 not only inhibited proliferation but also decreased invasion and migration in A549 cells. Most cells were intact (96.93%) under control conditions, but the number of intact cells decreased (84.8%) after 24 hours of treatment with UNBS5162, and the number of early and late apoptotic cells significantly increased (P < 0.05). Anti‐apoptotic protein Bcl‐2 expression in the UNBS5162 group was significantly decreased (P < 0.05), and expression of proapoptotic proteins Bim, Bax, and active caspase‐3 were significantly increased (P < 0.05) compared to the control. In the PI3K signaling pathway, phospo‐AKT and phospo‐mTOR levels were significantly decreased (P < 0.05), while S6K and Cyclin D1 protein levels were significantly decreased in UNBS5162 treated A549 cells (P < 0.05).ConclusionThese findings suggest that UNBS5162 could inhibit A549 cell proliferation and metastasis by inhibiting PI3K pathway mediated apoptosis.

UNBS5162 inhibits SKOV3 ovarian cancer cell proliferation by regulating the PI3K/AKT signalling pathway

“…Shukla et al (26) reported a number of applications of apoptosis in prostate cancer. Similarly, UNBS5162 could inhibit A549 non-small cell lung cancer cell proliferation by promoting apoptosis (11). In the present study, it was identified that 20 µM UNBS5162 exhibited a marked and similar inhibitory effect on, and low toxicity towards, SKOV3 ovarian cancer cells.…”

“…UNBS3157 was designed to avoid the blood toxicity of the clinical metabolism amonafide (10). UNBS3157 is rapidly hydrolysed in physiological saline to produce UNBS5162 which exhibits anticancer activity (11). UNBS5162, a novel type of naphthalimide, was used to avoid the specific effects of the metabolite amonafide, including haemotoxicity (12).…”

“…He et al (12) identified that UNBS5162 inhibits the proliferation of oesophageal cancer squamous cells through the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signalling pathway. Liu et al (11) identified that UNBS5162 inhibits the proliferation of human lung cancer cells by promoting cell apoptosis. It has also been identified that UNBS5162 has a therapeutic effect in the treatment of human retinoblastoma (13).…”

The mechanism of trans-δ-viniferin inhibiting the proliferation of lung cancer cells A549 by targeting the mitochondria

“…Further research found that most metabolites and proteins on the purine metabolism, arginine and proline metabolism, and PI3K-Akt signaling pathway of A549 cells were down-regulated after treatment with TVN, which implied that TVN could inhibit the normal metabolism of A549 cells and slow down the proliferation rate of A549 cells. The PI3K-Akt signaling pathway is widely deregulated in the human tumor spectrum ( Liu et al, 2018 ). In addition, it promotes the cell cycle, cell proliferation, cell survival, and anti-apoptosis, which is achieved by activating Akt and downstream targets FOXO-1, GSK-3, etc.…”