2'-Benzoyloxycinnamaldehyde-mediated DJ-1 upregulation protects MCF-7 cells from mitochondrial damage.
2'-Benzoyloxycinnamaldehyde (BCA) is a promising antitumor agent which induces cancer cells apoptosis via reactive oxygen species (ROS) generation. BCA shows more effective antiproliferation in MDA-MB-435 than in MCF-7 breast cancer cells. DJ-1 has been known to protect cells against oxidative stress as an antioxidant because of its cysteine residues sensitive to oxidative stress. In the present study, we evaluated the mechanism of DJ-1 for cell protection from oxidative stress after BCA treatment in MCF-7 cell. BCA upregulates the expression of DJ-1 in MCF-7 cells. However, DJ-1 expression decreased continuously for 24 h after BCA treatment in MDA-MB-435 cells. DJ-1 knockdown sensitized MCF-7 cells to BCA, on the contrary, DJ-1 overexpression induced MDA-MB-435 cells less sensitive to BCA. Confocal microscopic observation showed that only in MCF-7 cells BCA increased the overlapped signal between mitochondria and DJ-1 protein. Mitochondrial membrane potential (MMP) was decreased in MDA-MB-435 cells by BCA, and DJ-1 overexpression inhibited BCA-induced MMP decrease in these cells. On the contrary, DJ-1 knockdown in MCF-7 induced MMP perturbation by BCA. These findings suggest that DJ-1 upregulation protects MCF-7 cells from BCA via inhibiting mitochondrial damage.
Department of Oral Microbiology, School of Dentistry, Kyungpook National University, Daegu, South Korea.
Ismail Ahmed
IA
Ismail
Hye Suk
HS
Kang
Heon-Jin
HJ
Lee
Byoung-Mog
BM
Kwon
Su-Hyung
SH
Hong
D000171:Acrolein / Q000031:analogs & derivatives* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001565:Benzoates / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D020868:Gene Silencing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology*; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D000071617:Protein Deglycase DJ-1; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
C484327:2'-benzoyloxycinnamaldehyde; D000970:Antineoplastic Agents; D001565:Benzoates; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D034741:RNA, Small Interfering; D000171:Acrolein; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1