Effects of cigarette smoke extracts on the progression and metastasis of human ovarian cancer cells via regulating epithelial-mesenchymal transition.
Cigarette smoke (CS) contains over 60 well-established carcinogens, and there are strong links between these carcinogens and smoking-induced cancers. In this study we investigated whether three types of cigarette smoke extracts (CSEs), 3R4F (standard cigarette), CSE1 and CSE2 (two commercial cigarettes), affect the proliferation, migration, and invasive activity of BG-1 human ovarian cancer cells. All three types of CSEs increased BG-1 cell proliferation at nicotine concentrations of 1.5μM-2.1μM in a cell viability assay. The protein expressions of cyclin D1 and cyclin E1 were increased, while p21 and p27 expression was decreased by Western blot assay. However, they did not show a consistent dose-dependent tendency. The protein expressions of Bax and p53, pro-apoptotic genes, were also decreased by CSEs. The expression of E-cadherin, an epithelial marker, was reduced in the treatment of CSEs while the expression of its reverse transition marker, N-cadherin, was slightly increased by CSEs containing 2.1μM of nicotine, but a statistical significance was not observed. Epithelial-mesenchymal transition (EMT)-associated transcriptional factors, Snail and Slug, were also up-regulated by treatment with CSEs, indicating that CSEs can increase the EMT process in BG-1 ovarian cancer cells. In addition, CSEs increased the migratory and invasive propensity of cancer cells. These functional alterations were associated with changes in metastasis-related gene expression. Upon exposure to CSEs, the expression of MMP-9 and cathepsin D was increased. Taken together, we confirmed that CSEs increased the growth, migration, and invasion of human ovarian cancer cells by regulating cell cycle, apoptosis, EMT, and metastasis related cellular markers and signaling proteins. Based on the results, cigarette smokers of women might be at a higher risk of ovarian cancer than non-smokers.
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
So-Ye
SY
Jeon
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Ryeo-Eun
RE
Go
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Jae-Rim
JR
Heo
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Cho-Won
CW
Kim
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Kyung-A
KA
Hwang
Laboratory of Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea. Electronic address: kchoi@cbu.ac.kr.
Kyung-Chul
KC
Choi
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000473:pathology*; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products
D012906:Smoke
Cell cycle; Cigarette smoke extract; Epithelial-mesenchymal transition; Metastasis; Ovarian cancer cells