title: Phloretin exhibits an anticancer effect and enhances the anticancer ability of cisplatin on non-small cell lung cancer cell lines by regulating expression of apoptotic pathways and matrix metalloproteinases.
abstract: Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancer cases and the prognosis of NSCLC patients is unsatisfactory since 5-year survival rate of NSCLC is still as low as 11%. Natural compounds derived from plants with few or no side effects have been recognized as alternative or auxiliary cure for cancer patients. Phloretin is such an agent possessing various pharmacological activities; however, there is scarce information on its anticancer effects on NSCLC. It was evaluated and confirmed, in the present study, that phloretin inhibited proliferation and induced apoptosis in A549, Calu-1, H838 and H520 cells in a dose-dependent manner, phloretin also suppressed the invasion and migration of NSCLC cells. We further confirmed that phloretin dose-dependently suppressed the expression of Bcl-2, increased the protein expression of cleaved-caspase-3 and -9, and deregulated the expression of matrix metalloproteinases (MMP)-2 and -9 on gene and protein levels. Besides, evaluations revealed that phloretin enhanced the anticancer effects of cisplatin on inhibition of proliferation and induction of apoptosis in NSCLC cells. Moreover, phloretin facilitated the effects of cisplatin on deregulation of Bcl-2, MMP-2 and -9, and upregulation of cleaved-caspase-3 and -9. In conclusion, the present study demonstrated that phloretin possessed anticancer effects and enhanced the anticancer effects of cisplatin on NSCLC cell lines by suppressing proliferation, inducing apoptosis and inhibiting invasion and migration of the cells through regulating apoptotic pathways and MMPs.
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Ma
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Ruixuan
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Yandong
authors.initials: Y
authors.lastname: Nan
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Wangping
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Pharmacy, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Qingwei
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi'an 710038, P.R. China.
authors.forename: Faguang
authors.initials: F
authors.lastname: Jin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000503:physiopathology; D010693:Phloretin / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D053148:Caspase 3; D053453:Caspase 9; D020782:Matrix Metalloproteinases; D002945:Cisplatin; D010693:Phloretin