Kahweol induces apoptosis by suppressing BTF3 expression through the ERK signaling pathway in non-small cell lung cancer cells.

Abstract

Kahweol, a diterpene molecule, has antiproliferative effects on several types of human cancer cells, but whether it has apoptotic effect in non-small cell lung cancer (NSCLC) is not known. To explore this possibility, we incubated cells from two NSCLC cell lines, NCI-H358 and NCI‑H1299, with different concentrations of kahweol and used the MTS assay, DAPI staining, propidium iodide staining, Annexin V staining, immunocytochemical test, and western blot analysis to characterize this molecule and the signaling pathway underlying its effects. The kahweol-treated cells showed significantly decreased cell viability, increased nuclear condensation, and an increased number of Annexin V-positive NSCLC cells. Suppression of basic transcription factor 3 (BTF3) was followed by apoptosis induced by kahweol via the ERK-mediated signaling pathway in a dose- and time-dependent manner. In addition, kahweol modulated the protein expression of BTF3 genes involved in cell-cycle regulation and apoptosis-related proteins, resulting in apoptotic cell death. Our results collectively indicated that kahweol inhibited the proliferation of NSCLC cells through ERK-mediated signaling pathways and the downregulation of BTF3.

• Authors: Young-Joo Jeon, Woong Bang, Jin Hyoung Cho, Ra Ham Lee, Seok-Ho Kim, Minseok S Kim, Seon-Min Park, Jae-Cheon Shin, Hak-Jae Chung, Keon Bong Oh, Jae-Min Seo, Sungho Ko, Jung-Hyun Shim, Jung-Il Chae
• Journal: International journal of oncology (Int J Oncol) Vol. 49 Issue 6 Pg. 2294-2302 (Dec 2016) ISSN: 1791-2423 [Electronic] Greece
• PMID: 27748804 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Apoptosis Regulatory Proteins
• Diterpenes
• Nuclear Proteins
• Transcription Factors
• transcription factor BTF3
• kahweol
• Extracellular Signal-Regulated MAP Kinases

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Chemoprevention
• Diterpenes (pharmacology)
• Down-Regulation (drug effects)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Humans
• Lung Neoplasms (drug therapy, metabolism)
• MAP Kinase Signaling System (drug effects)
• Nuclear Proteins (biosynthesis)
• Transcription Factors (biosynthesis)