Quercetagetin-rich flavonoids from marigold induce apoptosis inhibit metastasis of non-small cell lung cancer via the p53/p21 signaling pathway
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic efficacy and severe side effects associated with conventional chemotherapy, creating an urgent need for safe and effective natural anti-tumor agents. Quercetagetin-rich marigold flavonoids (QG-MF), isolated from the lutein-extracted inflorescence residues ofL. (marigold), have been identified as bioactive polyphenols with potential anti-cancer properties, yet their anti-NSCLC activity and underlying molecular mechanisms remain elusive. Aim of the study This study aimed to investigate theandinhibitory effects of QG-MF on NSCLC. Methods experiments were performed on A549 and H661 NSCLC cell lines: cell proliferation was detected by CCK-8 assay; cell migration and invasion were evaluated via wound healing and Transwell assays, respectively; cell apoptosis and cycle distribution were analyzed by flow cytometry; the expression levels of p53/p21 signaling pathway-related proteins were determined by Western blot.anti-tumor efficacy of QG-MF was assessed using A549 NSCLC xenograft mouse models, with tumor volume and weight measured to evaluate tumor growth inhibition. Results QG-MF significantly suppressed proliferation, migration and invasion, and induced apoptosis as well as cell cycle arrest in A549 and H661 cells in a concentration-dependent manner. Mechanistically, QG-MF upregulated the expression of p53, p21, Bax and caspase-3, and downregulated Bcl-2 in NS
Abstract
Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide, with limited therapeutic efficacy and severe side effects associated with conventional chemotherapy, creating an urgent need for safe and effective natural anti-tumor agents. Quercetagetin-rich marigold flavonoids (QG-MF), isolated from the lutein-extracted inflorescence residues ofL. (marigold), have been identified as bioactive polyphenols with potential anti-cancer properties, yet their anti-NSCLC activity and underlying molecular mechanisms remain elusive. Aim of the study This study aimed to investigate theandinhibitory effects of QG-MF on NSCLC. Methods experiments were performed on A549 and H661 NSCLC cell lines: cell proliferation was detected by CCK-8 assay; cell migration and invasion were evaluated via wound healing and Transwell assays, respectively; cell apoptosis and cycle distribution were analyzed by flow cytometry; the expression levels of p53/p21 signaling pathway-related proteins were determined by Western blot.anti-tumor efficacy of QG-MF was assessed using A549 NSCLC xenograft mouse models, with tumor volume and weight measured to evaluate tumor growth inhibition. Results QG-MF significantly suppressed proliferation, migration and invasion, and induced apoptosis as well as cell cycle arrest in A549 and H661 cells in a concentration-dependent manner. Mechanistically, QG-MF upregulated the expression of p53, p21, Bax and caspase-3, and downregulated Bcl-2 in NSCLC cells. Furthermore, siRNA-mediated p53 silencing effectively abrogated the anti-proliferative and pro-apoptotic effects of QG-MF on NSCLC cells., QG-MF markedly inhibited the growth of A549 xenograft tumors in nude mice without obvious systemic toxicity. Conclusion Our findings demonstrate that QG-MF exerts potent anti-NSCLC activity by inducing apoptosis and inhibiting proliferation/metastasis via the p53/p21 signaling pathway.