Effects of a naphthoquinone analog on tumor growth and apoptosis induction.
Vitamin K-related analogs induce growth inhibition in various cancer cell lines. A naphthoquinone analog, termed 2,3-dichloro-5, 8-dihydroxy-1,4-naphthoquinone (DDN), induces apoptosis in human promyeloid leukemic HL-60 cells, and shows antitumor activity in vivo. Following treatment with DDN, evidence of apoptosis, including DNA fragmentation and cleavage of poly ADP ribose polymerase (PARP), was observed. DDN induced an upregulation of proapoptotic Bax protein, and Bid cleavage. Antiapoptotic Bcl-2 protein levels were not changed by DDN, but the expression of Bcl-xL was decreased. In addition, DDN reduced the mass of solid tumor in the Sarcoma 180 tumor-bearing mouse model. These results indicate that DDN exerts antitumor activity, which appears to be related to the induction of apoptosis by regulating Bcl-2 family proteins.
Kim
Hae Jong
HJ
Department of Biology, Division of Biochemistry, College of Pharmacy, Chung-Ang University, Seoul 156-756, Korea.
Mun
Jung Yee
JY
Chun
Young Jin
YJ
Choi
Kyung Hee
KH
Ham
Sung Wook
SW
Kim
Mie Young
MY
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D009285:Naphthoquinones / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012510:Sarcoma 180 / Q000188:drug therapy / Q000473:pathology
C462781:2,3-dichloro-5,8-dihydroxy-1,4-naphthoquinone; D000970:Antineoplastic Agents; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger