PMID- 28031751
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1555-8932 (Print)
IS  - 1865-3499 (Electronic)
IS  - 1555-8932 (Linking)
VI  - 11
DP  - 2016
TI  - Tocotrienols induce endoplasmic reticulum stress and apoptosis in cervical cancer 
      cells.
PG  - 32
LID - 10.1186/s12263-016-0543-1 [doi]
LID - 32
AB  - BACKGROUND: We have previously reported that gamma- and delta-tocotrienols (gamma- and delta-T3) 
      induce gene expression and apoptosis in human breast cancer cells (MDA-MB-231 and 
      MCF-7). This effect is mediated, at least in part, by a specific binding and 
      activation of the estrogen receptor-beta (ERbeta). Transcriptomic data obtained within 
      our previous studies, interrogated by different bioinformatic tools, suggested 
      the existence of an alternative pathway, activated by specific T3 forms and 
      leading to apoptosis, also in tumor cells not expressing ER. In order to confirm 
      this hypothesis, we conducted a study in HeLa cells, a line of human cervical 
      cancer cells void of any canonical ER form. RESULTS: Cells were synchronized by 
      starvation and treated either with a T3-rich fraction from palm oil (10-20 mug/ml) 
      or with purified alpha-, gamma-, and delta-T3 (5-20 mug/ml). alpha-tocopherol (TOC) was utilized 
      as a negative control. Apoptosis, accompanied by a significant expression of 
      caspase 8, caspase 10, and caspase 12 was observed at 12 h from treatments. The 
      interrogation of data obtained from transcriptomic platforms (NuGO Affymetrix 
      Human Genechip NuGO_Hs1a520180), further confirmed by RT-PCR, suggested that the 
      administration of gamma- and delta-T3 associates with Ca(2+) release. Data interrogation 
      were confirmed in living cells; in fact, Ca-dependent signals were observed 
      followed by the expression and activation of IRE-1alpha and of other molecules 
      involved in the unfolded protein response, the core pathway coping with 
      endoplasmic reticulum stress in eukaryotic cells, finally leading to apoptosis. 
      CONCLUSIONS: Our study demonstrates that gamma- and delta-T3 induce apoptosis also in 
      tumor cells lacking of ERbeta by triggering signals originating from endoplasmic 
      reticulum stress. Our observations suggest that tocotrienols could have a 
      significant role in tumor cell physiology and a possible therapeutic potential.
FAU - Comitato, Raffaella
AU  - Comitato R
AD  - Council for Agricultural Research and Economics - Food and Nutrition Research 
      Centre (C.R.E.A.-AN), via Ardeatina 546, 00178 Rome, Italy.
FAU - Guantario, Barbara
AU  - Guantario B
AD  - Council for Agricultural Research and Economics - Food and Nutrition Research 
      Centre (C.R.E.A.-AN), via Ardeatina 546, 00178 Rome, Italy.
FAU - Leoni, Guido
AU  - Leoni G
AD  - Department of Physics, Sapienza University of Rome, Piazzale Aldo Moro 5, 00185 
      Rome, Italy.
FAU - Nesaretnam, Kalanithi
AU  - Nesaretnam K
AD  - Malaysian Palm Oil Board, 6 Persiaran Institusi, Bandar Baru Bangi, 4300 
      Selangor, Malaysia.
FAU - Ronci, Maria Beatrice
AU  - Ronci MB
AD  - Council for Agricultural Research and Economics - Food and Nutrition Research 
      Centre (C.R.E.A.-AN), via Ardeatina 546, 00178 Rome, Italy.
FAU - Canali, Raffaella
AU  - Canali R
AD  - Council for Agricultural Research and Economics - Food and Nutrition Research 
      Centre (C.R.E.A.-AN), via Ardeatina 546, 00178 Rome, Italy.
FAU - Virgili, Fabio
AU  - Virgili F
AD  - Council for Agricultural Research and Economics - Food and Nutrition Research 
      Centre (C.R.E.A.-AN), via Ardeatina 546, 00178 Rome, Italy.
LA  - eng
PT  - Journal Article
DEP - 20161223
PL  - Germany
TA  - Genes Nutr
JT  - Genes & nutrition
JID - 101280108
PMC - PMC5180413
OTO - NOTNLM
OT  - Apoptosis
OT  - Endoplasmic reticulum stress
OT  - IRE-1alpha
OT  - Tocotrienol
OT  - XBP-1
EDAT- 2016/12/30 06:00
MHDA- 2016/12/30 06:01
PMCR- 2016/12/23
CRDT- 2016/12/30 06:00
PHST- 2015/12/18 00:00 [received]
PHST- 2016/10/02 00:00 [accepted]
PHST- 2016/12/30 06:00 [entrez]
PHST- 2016/12/30 06:00 [pubmed]
PHST- 2016/12/30 06:01 [medline]
PHST- 2016/12/23 00:00 [pmc-release]
AID - 543 [pii]
AID - 10.1186/s12263-016-0543-1 [doi]
PST - epublish
SO  - Genes Nutr. 2016 Dec 23;11:32. doi: 10.1186/s12263-016-0543-1. eCollection 2016.