title: Proteomic analysis of selective cytotoxic anticancer properties of flavonoids isolated from Citrus platymamma on A549 human lung cancer cells.
abstract: Citrus platymamma Hort. ex Tanaka (Byungkyul in Korean) has been used in Korean folk medicine for the treatment of inflammatory disorders and cancer. However, the molecular mechanism underlying the anticancer properties of flavonoids isolated from C. platymamma (FCP) remains to be elucidated. Therefore, the present study attempted to identify the key proteins, which may be important in the anticancer effects of FCP on A549 cells using a proteomic approach. FCP showed a potent cytotoxic effect on the A549 human lung cancer cells, however, it had no effect on WI‑38 human fetal lung fibroblasts at the same concentrations. Furthermore, 15 differentially expressed protein spots (spot intensities ≥2‑fold change; P<0.05) were obtained from comparative proteome analysis of two‑dimensional gel electrophoresis maps of the control (untreated) and FCP‑treated A549 cells. Finally, eight differentially expressed proteins, one of which was upregulated and seven of which were downregulated, were successfully identified using matrix‑assisted laser desorption/ionization time‑of‑flight/time‑of‑flight tandem mass spectrometry and peptide mass fingerprinting analysis. Specifically, proteins involved in signal transduction were significantly downregulated, including annexin A1 (ANXA1) and ANXA4, whereas 14‑3‑3ε was upregulated. Cytoskeletal proteins, including cofilin‑1 (CFL1), cytokeratin 8 (KRT8) and KRT79, and molecular chaperones/heat shock proteins, including endoplasmin, were downregulated. Proteins involved in protein metabolism, namely elongation factor Ts were also downregulated. Consistent with results of the proteome analysis, the immunoblotting results showed that 14‑3‑3ε was upregulated, whereas CFL1, ANXA4 and KRT8 were downregulated in the FCP‑treated A549 cells. The majority of the proteins were involved in tumor growth, cell cycle, apoptosis, migration and signal transduction. These findings provide novel insights into the molecular mechanisms underlying FCP-induced anticancer effects on A549 cells.
authors: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, Gyeongnam 660‑702, Republic of Korea.
authors: Arulkumar
authors: A
authors: Nagappan
authors: Research Institute of Life Science and College of Veterinary Medicine (BK21 Plus Project), Gyeongsang National University, Jinju, Gyeongnam 660‑701, Republic of Korea.
authors: Venu
authors: V
authors: Venkatarame Gowda Saralamma
authors: Research Institute of Life Science and College of Veterinary Medicine (BK21 Plus Project), Gyeongsang National University, Jinju, Gyeongnam 660‑701, Republic of Korea.
authors: Gyeong Eun
authors: GE
authors: Hong
authors: Research Institute of Life Science and College of Veterinary Medicine (BK21 Plus Project), Gyeongsang National University, Jinju, Gyeongnam 660‑701, Republic of Korea.
authors: Ho Jeong
authors: HJ
authors: Lee
authors: Department of Chemistry, Research Institute of Life Science, Gyeongsang National University, Jinju, Gyeongnam 660‑701, Republic of Korea.
authors: Sung Chul
authors: SC
authors: Shin
authors: Department of Nursing Science, International University of Korea, Jinju, Gyeongnam 660‑759, Republic of Korea.
authors: Eun Hee
authors: EH
authors: Kim
authors: Department of Internal Medicine, Institute of Health Sciences and Gyeongnam Regional Cancer Center, Gyeongsang National University School of Medicine, Jinju, Gyeongnam 660‑702, Republic of Korea.
authors: Won Sup
authors: WS
authors: Lee
authors: Research Institute of Life Science and College of Veterinary Medicine (BK21 Plus Project), Gyeongsang National University, Jinju, Gyeongnam 660‑701, Republic of Korea.
authors: Gon Sup
authors: GS
authors: Kim
mesh_terms: D000072283:A549 Cells; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002957:Citrus / Q000737:chemistry*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D040901:Proteomics / Q000379:methods; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D020543:Proteome