Beta-Lapachone Suppresses Non-small Cell Lung Cancer Proliferation through the Regulation of Specificity Protein 1.
Lung cancer is the leading cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) is the most common pathological type with a reported frequency of about 85% of all cases. Despite recent advances in therapeutic agents and targeted therapies, the prognosis for NSCLC remains poor, and therefore it is important to identify the biological targets of this complex disease since a blockade of such targets would affect multiple downstream signaling cascades. β-Lapachone (β-Lap) is an antiproliferative agent that selectively induces apoptosis-related cell death in a variety of human cancer cells. However, the mechanisms of its action require further investigation. In this study, we show that treatment with β-lap triggers apoptosis and cell-cycle arrest in two NSCLC cell lines: H1299 and NCI-H358. The transcription factor specificity protein 1 (Sp1) was markedly inhibited by β-lap in a dose- and time-dependent manner. Furthermore, β-lap modulated the protein expression levels of the Sp1 regulatory genes, including cell-cycle regulatory proteins and antiapoptotic proteins, resulting in apoptosis. Taken together, our results indicate that β-lap may be a potential antiproliferative agent candidate by inducing apoptotic cell death in NSCLC tissue through downregulation of Sp1.
Department of Dental Pharmacology, School of Dentistry and Institute of Oral Bioscience, BK21 plus, Chonbuk National University.
Young-Joo
YJ
Jeon
Woong
W
Bang
Yung Hyun
YH
Choi
Jung-Hyun
JH
Shim
Jung-Il
JI
Chae
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology*; D016329:Sp1 Transcription Factor / Q000378:metabolism*
D000970:Antineoplastic Agents; D009285:Naphthoquinones; D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C014638:beta-lapachone