title: 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 downregulating 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.
authors.affiliation: Department of Pediatrics, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.affiliation: Guangxi Province Key Laboratory, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P.R. China.
authors.forename: Jiagang
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Rongsheng
authors.initials: R
authors.lastname: Tong
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: He
authors.affiliation: Guangxi Province Key Laboratory, Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, P.R. China.
authors.forename: Jianzhen
authors.initials: J
authors.lastname: Lv
authors.affiliation: Institute of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Hailian
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Organ Transplantation, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Shaoping
authors.initials: S
authors.lastname: Deng
authors.affiliation: Department of Pediatrics, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Qi
authors.affiliation: Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Dingding
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Sichuan Academy of Medical Science and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610072, P.R. China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002945:Cisplatin / Q000627:therapeutic use / Q000633:toxicity; D019926:Cyclin B / Q000378:metabolism; D004359:Drug Therapy, Combination; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016328:NF-kappa B / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D019926:Cyclin B; D016328:NF-kappa B; D044004:Xanthones; C013592:mangiferin; D011493:Protein Kinase C; D016203:CDC2 Protein Kinase; D002945:Cisplatin