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Upon TUNEL assay, CS extract (3R4F; 0.3 and 2.1 \u03bcM) increased JEG\u20103 apoptosis. Western blot assay revealed that the protein expressions of p53, Bax, and CCAAT\u2010enhancer\u2010binding protein homologous protein (CHOP) increased, while the levels of Bcl\u20102 were reduced following CS extract treatment. Moreover, 2\u2032,7\u2032\u2010dichlorofluorescein diacetate (DCFH\u2010DA) assay revealed increased ROS production. Upon 3\u2010(4\u20105\u2010dimethylthiazol\u20102\u2010yl)\u20102.5\u2010dyhphenyltetrazolium bromide (MTT) assay, isoprene (IP), one of ingredients of CS, deceased JEG\u20103 cell viability (10<jats:sup>\u221211<\/jats:sup> to 10<jats:sup>\u22126<\/jats:sup> M). After based on the MTT assay, two IP concentrations of 10<jats:sup>\u221211<\/jats:sup> and 10<jats:sup>\u22128<\/jats:sup> M were selected and the protein expressions of cyclin D1, cyclin E1, p21, and p27 decreased in response to IP. Furthermore, IP showed the greatest increase in autophagy at 24 hours and further induction of cell death at 72 hours upon monodansylacadaverine and TUNEL assay. Western blot analysis confirmed the increase in autophagy markers, LC3\u03b2 and p62, as well as the increase or decrease of apoptosis markers p53, Bax, CHOP, and Bcl\u20102 in response to its treatments. In addition to confirming increases in ROS through DCFH\u2010DA, we also confirmed the expression of Nrf2, an antioxidant marker, and the expression of Kelch\u2010like ECH\u2010associated protein 1 (KEAP1), which specifically degrades Nrf2, by Western blot. Taken together, these results indicate that CS and IP may inhibit the development of placenta via activation of ROS by inducing apoptosis and autophagy by affecting the expression of KEAP1, which regulates Nrf2 expression.<\/jats:p>","DOI":"10.1002\/tox.22506","type":"journal-article","created":{"date-parts":[[2017,11,14]],"date-time":"2017-11-14T12:33:20Z","timestamp":1510662800000},"page":"178-190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Cigarette smoke extract and isoprene resulted in the induction of apoptosis and autophagy in human placenta choriocarcinoma JEG\u20103 cells"],"prefix":"10.1002","volume":"33","author":[{"given":"Hae\u2010Miru","family":"Lee","sequence":"first","affiliation":[{"name":"Laboratory of Biochemistry and Immunology, College of Veterinary Medicine Chungbuk National University Cheongju Chungbuk 28644 Republic of 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