Bisdemethoxycurcumin enhances X-ray-induced apoptosis possibly through p53/Bcl-2 pathway

Atsushi Enomoto; Junko Yamada; Akinori Morita; Kiyoshi Miyagawa

doi:10.1016/j.mrgentox.2016.12.005

Bisdemethoxycurcumin enhances X-ray-induced apoptosis possibly through p53/Bcl-2 pathway

Mutat Res Genet Toxicol Environ Mutagen. 2017 Mar:815:1-5. doi: 10.1016/j.mrgentox.2016.12.005. Epub 2017 Jan 11.

Authors

Atsushi Enomoto¹, Junko Yamada², Akinori Morita³, Kiyoshi Miyagawa⁴

Affiliations

¹ Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033, Japan. Electronic address: aenomoto-tky@umin.ac.jp.
² Radiation Safety Office, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033, Japan.
³ Department of Biomedical Science and Technology, Graduate School of Biomedical Sciences, Tokushima University, 3-18-15 Kuramotocho, Tokushima 770-8509, Japan.
⁴ Laboratory of Molecular Radiology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku Tokyo 113-0033, Japan.

PMID: 28283087
DOI: 10.1016/j.mrgentox.2016.12.005

Abstract

Bisdemethoxycurcumin (BDMC), which is isolated from the rhizomes of Curcuma longa, has anti-inflammatory and anti-carcinogenic activities. Here we found that BDMC enhanced X-ray-induced apoptosis in human T-cell leukemia MOLT-4 cells. Knockdown of p53 significantly attenuated the radiosensitizing effect of BDMC. However, BDMC did not enhance X-ray-mediated activation of the p53 signaling pathway via p53's transactivation or mitochondrial translocation. On the other hand, BDMC promoted the X-ray-induced dephosphorylation at Ser 70 in Bcl-2's flexible loop regulatory domain and Bcl-2 binding to p53. Overexpressing Bcl-2 completely blocked the BDMC's radiosensitization effect. Our results indicate that BDMC stimulates the dephosphorylation and p53-binding activity of Bcl-2 and suggest that BDMC may induce a neutralization of Bcl-2's anti-apoptotic function, thereby enhancing X-ray-induced apoptosis.

Keywords: Bcl-2; Bisdemethoxycurcumin (BDMC); Radiosensitization; p53/Bcl-2 binding.

MeSH terms

Apoptosis / drug effects*
Apoptosis / radiation effects
Cell Line, Tumor
Curcumin / analogs & derivatives*
Curcumin / pharmacology
Diarylheptanoids
Humans
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Tumor Suppressor Protein p53 / metabolism*
X-Rays

Substances

Diarylheptanoids
Proto-Oncogene Proteins c-bcl-2
Tumor Suppressor Protein p53
bisdemethoxycurcumin
Curcumin