Upregulation of PBR mRNA expression in human neuroblastoma cells by flavonoids.
To investigate the putative mediation of peripheral benzodiazepine receptor (PBR) in the cytotoxicity of flavonoids, in this study, modulatory effects of several flavonoids on the lipid peroxide (LPO) production and PBR mRNA expression of human neuroblastoma cells were observed. Elevated levels of peroxidated products in cancer cells may activate pro-apoptotic and anti-proliferative signaling pathways. Treatment of 10(-6) M 4'-chlorodiazepam and PK 11195 ligands of the PBR for 6 days enhanced the generation of LPO of the human neuroblastoma cells. Several flavonoids, well-known cytotoxic substances, potentiated the enhancement of LPO production by PBR ligands. Treatment of 10(-6) M flavonoids for 6 days elevated the expression of PBR mRNA in cells. These findings indicate that the potential of flavonoids to induce apoptosis in cancer cells is strongly associated with their PBR-inducing properties, thereby providing a new mechanism by which polyphenolic compounds may exert their cancer-preventive and anti-neoplastic effects.
Ha
Jeoung-Hee
JH
Department of Pharmacology, College of Medicine, Kyungpook National University, Taegu 700-422, Republic of Korea. jhha4834@mail.knu.ac.kr
Lee
Jae-Tae
JT
Cho
Ihn-ho
IH
Chun
Kyung-Ah
KA
Park
Gi-Eun
GE
Choi
Hyung-Chul
HC
Lee
Kwang-Youn
KY
Kim
Sang-Hyun
SH
Suk
Kyoungho
K
Kim
In-Kyeom
IK
Lee
Maan-Gee
MG
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001570:Benzodiazepinones / Q000819:agonists / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D017931:DNA Primers; D005419:Flavonoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008054:Lipid Peroxides; D009447:Neuroblastoma / Q000473:pathology; D008517:Phytotherapy; D010946:Plants, Medicinal; D012333:RNA, Messenger / Q000032:analysis; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D001570:Benzodiazepinones; D017931:DNA Primers; D005419:Flavonoids; D008054:Lipid Peroxides; D012333:RNA, Messenger; D011963:Receptors, GABA-A