Molecular mechanisms underlying mangiferin-induced apoptosis and cell cycle arrest in A549 human lung carcinoma cells

Abstract

Mangiferin, which is a C-glucosylxanthone (1,3,6,7-tetrahydroxyxanthone-C2-β-D-glucoside) purified from plant sources, has recently gained attention due to its various biological activities. The present study aimed to determine the apoptotic effects of mangiferin on A549 human lung adenocarcinoma cells. In vitro studies demonstrated that mangiferin exerted growth-inhibitory and apoptosis-inducing effects against A549 cells. In addition, mangiferin exhibited anti-tumor properties in A549 xenograft mice in vivo. Mangiferin triggered G2/M phase cell cycle arrest via down-regulating the cyclin-dependent kinase 1-cyclin B1 signaling pathway, and induced apoptotic cell death by inhibiting the protein kinase C-nuclear factor-κB pathway. In addition, mangiferin was able to enhance the antiproliferative effects of cisplatin on A549 cells, thus indicating the potential for a combined therapy. Notably, mangiferin exerted anticancer effects in vivo, where it was able to markedly decrease the volume and weight of subcutaneous tumor mass, and expand the lifespan of xenograft mice. The present study clarified the molecular mechanisms underlying mangiferin-induced antitumor activities, and suggested that mangiferin may be considered a potential antineoplastic drug for the future treatment of cancer.

Quinalizarin exerts an anti-tumour effect on lung cancer A549 cells by modulating the Akt, MAPK, STAT3 and p53 signalling pathways

“…CDK2/4/6 and cyclin D1/E are known to be involved in the regulation of G 0 /G 1 phase. Because activation of the CDK/cyclin complex initiates entry into G 1 phase, the G 0 /G 1 transition usually requires a functional CDK/cyclin complex (34). Our results indicated that quinalizarin induced A549 cell cycle arrest at G 0 /G 1 phase by suppressing CDK2/4/6 and cyclin D1/E and increasing p21 and p27 protein expression levels.…”

Potential Therapeutic Value of Mangiferin for Lung Adenocarcinoma (Luad): A Comprehensive Study Based on in Vitro Experiments and Bioinformatics

“…In terms of antineoplastic mechanisms, mangiferin has been shown to act on multiple molecular targets, which mediate the underlying biological signaling processes that inhibit the initiation, promotion, and metastasis of cancer [14][15][16][17][18][19][20]. For lung cancer, studies have found that decreased activities of some biochemical pathways in lung cancer-bearing animals were prevented after pre-and posttreatment with mangiferin and even approached normal control animal values [21][22][23][24][25]. It was also shown that the anticancer effect of mangiferin was more pronounced when used as a chemopreventive agent, rather than as a chemotherapeutic agent, against B(a)P-induced lung carcinogenesis [26].…”

“…It was also shown that the anticancer effect of mangiferin was more pronounced when used as a chemopreventive agent, rather than as a chemotherapeutic agent, against B(a)P-induced lung carcinogenesis [26]. In addition, mangiferin was able to decrease the tumor mass by helping the cisplatin with antiproliferative effects on A549 cells [25]. According to recent ndings by Grauzdytė D et al, mangiferin ameliorates oxidative stress, accelerates the wound healing process and restores the proliferation rate in polycyclic aromatic hydrocarbon-exposed bronchial epithelium [27].…”

Tetrahydrocurcumin‑induced autophagy via suppression of PI3K/Akt/mTOR in non‑small cell lung carcinoma cells

“…The prognosis for lung cancer is unfavorable, and novel therapeutic strategies to improve the outcome of patients with NSCLC are required. Traditional Chinese medicine is a source of novel compounds with antineoplastic activity, including isocryptotanshinone, mangiferin and xanthatin (4)(5)(6). Tetrahydrocurcumin (THC) is a traditional Chinese medicine isolated from Curcuma wenyujin (Chen & Ling, 1981).…”