Objective To investigate the protective effect of quercetin against benzo(a)pyrene (BaP)-induced damage in human lung adenocarcinoma A549 cells by regulating Drp1 expression to improve mitophagy. Methods The A549 cells were randomly divided into 4 groups: a control group (normal culture), a BaP group (treated with BaP), a BaP+Quercetin group (quercetin intervention + BaP treatment), and a BaP+Mdivi-1 group (Drp1 inhibitor Mdivi-1 + BaP treatment). Cell viability was measured by CCK8 assay, apoptosis was observed by TUNEL staining, cell volume was observed by phalloidin staining, changes in organelles were examined by transmission electron microscopy, and the expression levels of autophagy-related proteins (Drp1, PINK1, Parkin) was analyzed by Western blotting. Results Compared with the Control group, the BaP group showed reduced cell viability (P<0.05), increased apoptosis rate and elevated expression of autophagy-related proteins (Drp1, PINK1, Parkin) increased (P<0.05). Compared with the BaP group, the cell viability in the BaP + Quercetin group and the BaP + Mdivi-1 group increased (P<0.05), and the apoptosis rate and the expression of autophagy-related proteins (Drp1, PINK1, Parkin) decreased (P<0.05). Conclusions Quercetin can regulate the expression of Drp1 to improve abnormal mitophagy and achieve the protective effect on A549 cells damage induced by BaP.
Key words
Drp1 /
mitophagy /
quercetin /
benzo(a)pyrene /
lung adenocarcinoma
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References
[1] Kasala E R, Bodduluru L N, Barua C C, et al. Benzo(a)pyrene induced lung cancer: role of dietary phytochemicals in chemoprevention[J]. Pharmacol Rep, 2015, 67(5): 996-1009.
[2] Hoffmann D, Hoffmann I, El-Bayoumy K. The less harmful cigarette: a controversial issue. A tribute to Ernst L. Wynder[J]. Chem Res Toxicol, 2001, 14(7): 767-790.
[3] Zuo J, Brewer D S, Arlt V M, et al. Benzo pyrene-induced DNA adducts and gene expression profiles in target and non-target organs for carcinogenesis in mice[J]. BMC Genomics, 2014, 15(1): 880.
[4] Mori M P, Penjweini R, Knutson J R, et al. Mitochondria and oxygen homeostasis[J]. FEBS J, 2022, 289(22): 6959-6968.
[5] Barkauskas C E, Cronce M J, Rackley C R, et al. Type 2 alveolar cells are stem cells in adult lung[J]. J Clin Invest, 2013, 123(7):3025-3036.
[6] Witschi H. Responses of the lung to toxic injury[J]. Environ Health Perspect, 1990, 85:5-13.
[7] Ma L, Feugang J M, Konarski P, et al. Growth inhibitory effects of quercetin on bladder cancer cell[J]. Front Biosci, 2006, 11:2275-2285.
[8] Granato M, Rizzello C, Gilardini Montani M S, et al. Quercetin induces apoptosis and autophagy in primary effusion lymphoma cells by inhibiting PI3K/AKT/mTOR and STAT3 signaling pathways[J]. J Nutr Biochem, 2017, 41: 124-136.
[9] 朱小艳. 苯并芘对肺泡Ⅱ型上皮细胞A549氧化应激的影响[D]. 长沙:中南大学, 2011.
[10] 李南燕. 苯并芘(BaP)通过ANT1-PARKIN通路影响孕早期卵巢线粒体自噬[D].重庆:重庆医科大学, 2021.
[11] 许禄华. 保元活络法改善心肌缺血再灌注损伤的作用和机制研究[D]. 广州:广州中医药大学, 2021.
[12] 袁雅璐, 程远雄, 曹 静, 等. 苯并芘激活ERK1/2信号通路促进气道平滑肌细胞外基质蛋白沉积对气道重塑的影响[J]. 重庆医学, 2017, 46(16): 2174-2177.
[13] Wang Z. Mechanisms of the synergistic lung tumorigenic effect of arsenic and benzo(a)pyrene combined- exposure[J]. Semin Cancer Biol, 2021, 76:156-162.
[14] 连立芬.山奈酚抑制BaP致HTR8-SVneo细胞氧化损伤的研究[D].石家庄:河北医科大学,2014.
[15] Xu J, Kitada M, Ogura Y, et al. Relationship between autophagy and metabolic syndrome characteristics in the pathogenesis of atherosclerosis[J]. Front Cell Dev Biol, 2021, 9: 641852.
[16] Li D, You Y, Bi F F, et al. Autophagy is activated in the ovarian tissue of polycystic ovary syndrome[J]. Reproduction, 2018, 155(1): 85-92.
[17] Abate M, Festa A, Falco M, et al. Mitochondria as playmakers of apoptosis, autophagy and senescence[J]. Semin Cell Dev Biol, 2020, 98: 139-153.
[18] Caroppi P, Sinibaldi F, Fiorucci L, et al. Apoptosis and human diseases: mitochondrion damage and lethal role of released cytochrome C as proapoptotic protein[J]. Curr Med Chem, 2009, 16(31):4058-4065.
[19] 吴建军.槲皮素通过Parkin调控C2C12细胞成肌分化中线粒体自噬机制研究[D].广州:广州中医药大学, 2024.
[20] 赵继辉. 槲皮素通过SIRT3激活线粒体自噬改善骨质疏松的机制研究[D].沈阳:中国医科大学, 2024.
[21] 文兰香, 覃世运, 陈丽君. 槲皮素调控AMPK/mTOR通路对肺癌A549细胞自噬的影响[J]. 中国免疫学杂志, 2020, 36(19): 2375-2379.