title: 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.
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 μM) 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.
authors.affiliation: College of Oriental Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.forename: Eun Jung
authors.initials: EJ
authors.lastname: Sohn
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Shin
authors.forename: Duckgue
authors.initials: D
authors.lastname: Lee
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.forename: Deok-Beom
authors.initials: DB
authors.lastname: Jung
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Kim
authors.forename: Miyong
authors.initials: M
authors.lastname: Yun
authors.forename: Hyo-Jeong
authors.initials: HJ
authors.lastname: Lee
authors.forename: Yong Koo
authors.initials: YK
authors.lastname: Park
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim