Synergistic effect of combined treatment with gamma-tocotrienol and statin on human malignant mesothelioma cells

Guligena Tuerdi; Saki Ichinomiya; Hiromi Sato; Sana Siddig; Eriko Suwa; Hiroki Iwata; Tomohiro Yano; Koichi Ueno

doi:10.1016/j.canlet.2013.07.015

Synergistic effect of combined treatment with gamma-tocotrienol and statin on human malignant mesothelioma cells

Cancer Lett. 2013 Oct 1;339(1):116-27. doi: 10.1016/j.canlet.2013.07.015. Epub 2013 Jul 20.

Authors

Guligena Tuerdi¹, Saki Ichinomiya, Hiromi Sato, Sana Siddig, Eriko Suwa, Hiroki Iwata, Tomohiro Yano, Koichi Ueno

Affiliation

¹ Department of Geriatric Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba-shi, Chiba 260-8675, Japan.

PMID: 23879968
DOI: 10.1016/j.canlet.2013.07.015

Abstract

The present study is the first to demonstrate the synergetic effect of statins (atorvastatin and simvastatin) and gamma-tocotrienol (γ-T3) on human malignant mesothelioma (MM). Statin + γ-T3 combinations induced greater cell growth inhibition more than each single treatment via inhibition of mevalonate pathway, a well-known target of both γ-T3 and statins. γ-T3 was necessary for endoplasmic reticulum stress markers CHOP and GRP78, whereas an intrinsic apoptotic marker, caspase 3 activation was induced only in the presence of statins. Overall, the combination of γ-T3 and statins could be useful for MM therapy and functions in a complementary style.

Keywords: Apoptosis; Gamma tocotrienol; Mesothelioma; Mevalonate pathway; Statin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / drug effects
Atorvastatin
Caspase 3 / metabolism
Cell Line, Tumor
Cell Proliferation / drug effects
Chromans / administration & dosage
Chromans / pharmacology*
Chromans / toxicity
Drug Synergism
Endoplasmic Reticulum Chaperone BiP
Endoplasmic Reticulum Stress / drug effects
Enzyme Activation / drug effects
Heptanoic Acids
Humans
Hydroxymethylglutaryl CoA Reductases / genetics
Hydroxymethylglutaryl CoA Reductases / metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors / administration & dosage
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
Hydroxymethylglutaryl-CoA Reductase Inhibitors / toxicity
Mesothelioma / genetics
Mesothelioma / metabolism*
Metabolic Networks and Pathways / drug effects
Mevalonic Acid / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism
Pyrroles
Simvastatin
Vitamin E / administration & dosage
Vitamin E / analogs & derivatives*
Vitamin E / pharmacology
Vitamin E / toxicity

Substances

Chromans
Endoplasmic Reticulum Chaperone BiP
HSPA5 protein, human
Heptanoic Acids
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Proto-Oncogene Proteins c-bcl-2
Pyrroles
Vitamin E
plastochromanol 8
Atorvastatin
Simvastatin
Hydroxymethylglutaryl CoA Reductases
Caspase 3
Mevalonic Acid