Acetyl-11-keto-β-boswellic acid enhances the cisplatin sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy suppression via p21-dependent signaling pathway

Abstract

Cisplatin-based therapy is a widely used chemotherapeutic regimen for non-small cell lung cancer (NSCLC); however, drug resistance limits its efficacy. Acetyl-11-keto-β-boswellic acid (AKBA), a bioactive compound from frankincense, has been shown to exert anti-cancer effects. The aim of this study is to explore the potential of AKBA in combination with cisplatin as a new regimen for NSCLC. CCK8 assay and clone formation assay were used to determine the effects of AKBA in combination with cisplatin on cell viability of NSCLC cell lines. A three-dimensional spherification assay was used to simulate in vivo tumor formation. Flow cytometry was performed to examine cell cycle distribution and the percentages of apoptotic cells. The associated proteins and mRNA of cell cycle, apoptosis, and autophagy were measured by western blotting and real-time fluorescence quantitative PCR. Immunofluorescence assay was used to test apoptotic nuclei and autolysosome. Small interfering RNA experiments were used to silence the expression of p21. Combination treatment of AKBA and cisplatin inhibited cell viability, clone formation, and three-dimensional spherification, enhanced G0/G1 phase arrest, increased the percentages of apoptotic cells, and decreased the ratio of positive autolysosomes, compared with cisplatin alone. AKBA in combination with cisplatin suppressed the protein expressions of cyclin A2, cyclin E1, p-cdc2, CDK4, Bcl-xl, Atg5, and LC3A/B, and upregulated p27 and p21 mRNA levels in A549 cells. Downregulation of p21 decreased G0/G1 phase arrest and the percentages of apoptotic cells, and promoted autophagy in NSCLC A549 cells. Our study demonstrates that AKBA enhances the cisplatin sensitivity of NSCLC cells and that the mechanisms involve G0/G1 phase arrest, apoptosis induction, and autophagy suppression via targeting p21-dependent signaling pathway.

[Retracted] Irisin Attenuates Oxidative Stress, Mitochondrial Dysfunction, and Apoptosis in the H9C2 Cellular Model of Septic Cardiomyopathy through Augmenting Fundc1‐Dependent Mitophagy

“…Then, the membrane was incubated with the primary antibody overnight at 4°C. GAPDH was used as internal reference and probed with anti-GAPDH antibody [ 36 ]. The membranes were incubated with HRP-conjugated secondary antibody at room temperature for 2 h. Finally, the membranes were developed using the ECL substrate reagent kit (GE Healthcare) and analyzed using the Gel Doc XR imaging system (Bio-Rad, USA).…”

Deubiquitinase USP35 modulates ferroptosis in lung cancer via targeting ferroportin

“…Cell cycle was analyzed by propidium iodide (PI) as previously described. [42][43][44] In brief, the cells were fixed in 70% ethanol at -20 • C overnight and then incubated with PI/RNase Staining Buffer (BD Bioscience) at 37 • C for 30 min. Eventually, the DNA content was evaluated using the flow cytometry and quantified by Modfit software.…”

miR-6077 promotes cisplatin/pemetrexed resistance in lung adenocarcinoma via CDKN1A/cell cycle arrest and KEAP1/ferroptosis pathways

“… 22 , 24 , 41 , 42 , 43 However, the exact function of CDKN1A in the regulation of cancer cell sensitivity to treatments that exert cytotoxicity by interfering with the stability and synthesis of genetic materials varies among tumor types. 18 , 29 , 44 , 45 , 46 This variation may be explained by the participation of CDKN1A as a master effector in multiple tumor-suppressor pathways that are tightly intertwined, such as cell-cycle arrest, apoptosis, senescence, and DNA repair. 24 Through bioinformatic analysis based on both RNA-seq and scRNA-seq, we observed the activation of several biological processes involved in cell-cycle progression.…”