Protective effect of luteolin on cigarette smoke extract-induced cellular toxicity and apoptosis in normal human bronchial epithelial cells via the Nrf2 pathway.
Luteolin, one of the most common abundant flavonoids in vegetables and herbs, has antitumor effects on various tumors by inducing apoptosis, antioxidant effects and inhibition of angiogenesis. However, the potential chemoprevention of luteolin on lung cell damage and its related mechanism(s) are not fully known. The present study evaluated the protective effects of luteolin on cigarette smoke extract (CSE)-induced toxicity and apoptosis in normal human bronchial epithelial (NHBE) cells and explored its underlying mechanism(s). MTT assay showed that pretreatment with luteolin increased CSE-decreased cell viability (p<0.05). Luteolin increased cellular glutathione (GSH) levels but decreased reactive oxygen species (ROS) generation (p<0.05). Cytometry assay and western blot analysis showed that luteolin attenuated CSE-induced apoptosis and apoptosis‑related protein activation, including caspase‑3, -8 and -9 (p<0.05). The expression of CSE-induced
quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1) were decreased significantly by luteolin (p<0.05). Furthermore, luteolin attenuated CSE-induced apoptosis, noticeably reduced CSE-induced expression of NF-E2-related factor 2 (Nrf2), NQO1 and HO-1 using a small interfering RNA (siRNA) transfection assay. The data demonstrated that CSE-induced oxidative damage and apoptosis through the Nrf2 pathway was inhibited by luteolin and it may serve as a chemopreventive agent for the prevention and treatment of lung cancer.
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Xiaobin
X
Tan
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Ping
P
Jin
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Liang
L
Feng
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Jie
J
Song
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
E
E
Sun
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Wenbo
W
Liu
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Luan
L
Shu
Key Laboratory of New Drug Delivery System of Chinese Materia Medica, Jiangsu Provincial Academy of Chinese Medicine, Nanjing, Jiangsu 210028, P.R. China.
Xiaobin
X
Jia
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D000975:Antioxidants; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D012906:Smoke; D047311:Luteolin