Melatonin Suppresses the Expression of 45S Preribosomal RNA and Upstream Binding Factor and Enhances the Antitumor Activity of Puromycin in MDA-MB-231 Breast Cancer Cells. (7th April 2013)

• Record Type: Journal Article
• Authors: Jung, Ji Hoon; Sohn, Eun Jung; Shin, Eun Ah; Lee, Duckgue; Kim, Bonglee; Jung, Deok-Beom; Kim, Ji-Hyun; Yun, Miyong; Lee, Hyo-Jeong; Park, Yong Koo; Kim, Sung-Hoon
• Other Names: Eddouks Mohamed Academic Editor.
• Is Part Of: Evidence-based complementary and alternative medicine. Volume 2013(2013)
• Publication Date: 2013-04-07
• Subjects: Alternative medicine -- Periodicals; 615.505
• DOI: 10.1155/2013/879746
• Languages: English
• ISSNs: 1741-427X

Abstract

Abstract : Since the dysregulation of ribosome biogenesis is closely associated with tumor progression, in the current study, the critical role of ribosome biogenesis related signaling was investigated in melatonin and/or puromycin induced apoptosis in MDA-MB-231 breast cancer cells. Despite its weak cytotoxicity, melatonin from 3 mM attenuated the expression of 45S pre-ribosomal RNA (pre-rRNA), UBF as a nucleolar transcription factor, and fibrillarin at mRNA level and consistently downregulated nucleolar proteins such as UBF and fibrillarin at protein level in MDA-MB-231 cells. Furthermore, immunofluorescence assay revealed that UBF was also degraded by melatonin in MDA-MB-231 cells. In contrast, melatonin attenuated the expression of survival genes such as Bcl-xL, Mcl-1, cyclinD1, and cyclin E, suppressed the phosphorylation of AKT, mTOR, and STAT3, and cleaved PARP and activated caspase 3 only at a high concentration of 12 mM. However, combined treatment of melatonin (3 mM) and puromycin (1 μ M) synergistically inhibited viability, attenuated the expression of 45S pre-rRNA and UBF, and consistently downregulated UBF, XPO1 and IPO7, procaspase 3, and Bcl-xL in MDA-MB 231 cells. Overall, these findings suggest that melatonin can be a cancer preventive agent by combination with puromycin via the inhibition of 45S pre-rRNA and UBF in MDA-MB 231 breast cancer cells.