R. Suginaka et al., Induction of apoptosis in human pancreatic carcinoma cells by a synthetic bleomycin-like ligand, JPN J CANC, 89(9), 1998, pp. 947-953
Histidine-pyridine-histidine-3 (HPH-3) is an oxygen-activating ligand based
on the structure of bleomycin, HPH-3 induced the death of human pancreatic
adenocarcinoma AsPC-1 cells in 24 h, causing apoptotic morphology and inte
rnucleosomal degradation of DNA, HPH-3-induced cell death was not inhibited
by antioxidants such as reduced glutathione and N-acetylcysteine, whereas
hydrogen peroxide-induced cell death was inhibited by them, indicating that
hydrogen peroxide is not involved in the induction of apoptosis by HPH-3.
Induction of apoptosis by HPH-3 was inhibited by zinc and copper ions, indi
cating that chelation with ferrous ion is responsible for induction of apop
tosis, as is the case in chelation by bleomycin to cleave DNA, Bleomycin A,
and its fragment having no DNA-binding region, glycopeptide-3, did not ind
uce apoptosis in AsPC-1 cells, Bleomycin A, induced G2/M block in flow-cyto
metric analysis, but HPH-3 did not and instead induced an apoptotic pre-G1
peak. Thus, HPH-3 induced apoptosis in human pancreatic carcinoma cells, wh
ich is a unique characteristic among bleomycin-related compounds.