Cytotoxic activity of deferiprone, maltol and related hydroxyketones against human tumor cell lines.

Abstract

Hydroxyketone chelators, deferiprone (HK1), maltol (HK3) and their related compounds (HK2, 4-8), were characterized for their cytotoxic profiles against oral human normal and tumor cells. Most hydroxyketones except HK6 showed relatively higher tumor-specific cytotoxicity. Deferiprone (HK1), which showed the highest tumor specificity, had 10 times higher cytotoxicity than maltol (HK3) in both human promyelocytic leukemia HL-60 and human oral squamous cell carcinoma HSC-2 cell lines. The cytotoxic activity of HK1 against HL-60 and HSC-2 cells was reduced in the presence of FeCl3, while that of HK3 was significantly increased by FeCl3. Agarose gel electrophoresis showed that HK1 induced internucleosomal DNA fragmentation in HL-60 cells, but the addition of FeCl3 inhibited the DNA fragmentation. HK3 did not induce DNA fragmentation in HL-60 cells, regardless of the presence or absence of FeCl3. In HSC-2 cells, HK1 and 3 did not induce DNA fragmentation in the presence or absence of FeCl3. Colorimetric protease assay showed that HK1 activated the caspase 3, 8 and 9 in HL-60 cells. On the other hand, HK3 did not activate the caspase 3, 8 and 9 in HL-60 cells, but activated the caspase 3 only slightly in the presence of FeCl3. HK1 and 3 also activated the caspase 3, 8 and 9 in HSC-2 cells, but to a lesser extent. The present study suggested that the antitumor activity of hydroxyketones may be modified by Fe3+ concentration.

• Authors: Eiji Yasumoto, Kensuke Nakano, Tohru Nakayachi, Sufi Reza Md Morshed, Ken Hashimoto, Hirotaka Kikuchi, Hirofumi Nishikawa, Masami Kawase, Hiroshi Sakagami
• Journal: Anticancer research (Anticancer Res) 2004 Mar-Apr Vol. 24 Issue 2B Pg. 755-62 ISSN: 0250-7005 [Print] Greece
• PMID: 15161023 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Chelating Agents
• Ketones
• Monoterpenes
• Pyridones
• Pyrones
• Deferiprone
• maltol
• Mimosine
• kojic acid
• Tropolone
• Caspases
• beta-thujaplicin

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Carcinoma, Squamous Cell (drug therapy)
• Caspases (metabolism)
• Cell Line, Tumor
• Chelating Agents (chemistry, pharmacology)
• DNA Fragmentation (drug effects)
• Deferiprone
• Drug Screening Assays, Antitumor
• Enzyme Activation (drug effects)
• HL-60 Cells
• Humans
• Ketones (chemistry, pharmacology)
• Mimosine (pharmacology)
• Monoterpenes (pharmacology)
• Mouth Neoplasms (drug therapy)
• Pyridones (pharmacology)
• Pyrones (pharmacology)
• Structure-Activity Relationship
• Tropolone (analogs & derivatives, pharmacology)