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

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.

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

Мелатонин подавляет экспрессию 45S Preribosomal РНК и Upstream связывающий фактор и повышает противоопухолевую активность пуромицина в MDA-MB- 231 клеток рака молочной железы .
Юнг JH , Сон Е.Ю., Шин Е.А., Ли D , Ким B , Юнг DB , Ким Д.Х. , Юн Мин , Ли HJ , Парк Ю.К., Ким SH Поскольку нарушение регуляции биогенеза рибосом тесно связана с опухолевой прогрессии , в данном исследовании , была исследована критическая роль биогенеза рибосом , связанных с сигнализацией в мелатонина и / или пуромицина индуцированного апоптоза в MDA-MB- 231 клеток рака молочной железы . Несмотря на слабый цитотоксичности , мелатонин от 3 мм ослабляется экспрессию 45S предварительно рибосомной РНК ( пре-рРНК ) , UBF как ядрышек фактора транскрипции , и фибрилларина на уровне мРНК и последовательно подавляется ядрышковых белков, таких как UBF и фибрилларина на уровне белка в MDA-MB- 231 клеток. Кроме того, иммунофлуоресценции показали, что UBF также понижена мелатонина в MDA-MB- 231 клеток. В противоположность этому, ослаблен мелатонин экспрессию генов выживания , таких как Bcl- XL, Mcl-1 , cyclinD1 и циклин Е, подавляется фосфорилирование AKT , MTOR и STAT3 и расщепляется PARP и активированный каспазы 3 только при высокой концентрации 12 мм. Однако комбинированное лечение мелатонина (3 мм) и пуромицин (1 мкМ) синергически тормозится жизнеспособность , ослабляется экспрессию 45S пре-рРНК и UBF , и последовательно подавляется UBF , XPO1 и IPO7 , прокаспазы 3 и Bcl -XL в MDA - MB 231 клеток. В целом, эти результаты показывают, что мелатонин может быть рак профилактический агент по сочетании с пуромицин через ингибирование 45S рРНК предварительно UBF и в MDA-MB 231 клеток рака молочной железы

http://www.melatonin.com/

Dosages

There is no established dosage for melatonin that is widely accepted. In addition, experts note that most brands contain impurities that cannot be characterized, as well as dissimilar amounts of actual hormone. When buying in America, please note that the U.S. Food and Drug Administration does not strictly regulate herbs and supplements. There is no guarantee of strength, purity or safety of products, and effects may vary. You should read product labels, and discuss doses with a qualified healthcare provider before starting therapy. Below are dosages used by researchers exploring various disorders. (Summarized from the Mayo Clinic.)
Adults (18 years and older)
Disorder	Dosage (milligrams)	When
Alzheimer's disease (sleep disturbances)	0.5	nightly, 1 hr before bedtime
Bipolar disorder (sleep disturbances)	10	nightly by mouth
Cancer	10 to 50, most commonly 20	nightly
Circadian rhythm entraining (in blind persons)	5 to10	nightly
Critical Illness / ICU sleep disturbance	3	nightly
Delayed sleep phase syndrome	5	5 hrs before bedtime
Depression (sleep disturbances)	5	nightly
Headache prevention	5 to 10	nightly
Hypertension	1 to 3	short periods of time
Insomnia in the elderly	3 to 5	30 - 120 min before bedtime
Insomnia of unknown origin (in the non-elderly)	1 to 5	nightly
Jet lag	0.1 to 0.5, 5 and 8	Target bedtime at the destination
Schizophrenia (sleep disturbances)	2	(not stated)
Seasonal affective disorder	0.25 to 5	daily
Sleep enhancement in healthy people	0.1 to 6	30 - 60 minutes before bedtime
Children (younger than 18 years) There is limited study of melatonin supplements in children, and safety is not established. Use of melatonin should be discussed with the child's physician prior to starting.
Disorder	Dosage (milligrams)	When
Circadian rhythm entraining in blind children	2.5 to 10	nightly
Preoperative anxiety	0.1, 0.25 or 0.5 per kilogram (of child’s weight?)	(not stated)
Seizure disorder in children	5 to 10	nightly
Sleep disturbances in children with neuro-psychiatric disorders (mental retardation, autism, psychiatric disorders)	0.5 to 10	nightly

Br J Cancer. 2013 May 28;108(10):2005-12. doi: 10.1038/bjc.2013.188. Epub 2013 Apr 30.