Characterization of the anticancer activity of DW2282, a new anticancer agent.
DW2282 [(S)-(+)-4-phenyl-1-[N-(4-aminobenzoyl) indoline-5-sulfonyl]-4,5-dihydro-2-imidazolone].hydrochloride] was derived from diarylsulfonylurea and was identified as a prominent new anticancer agent. We examined the characteristics of DW2282 activity on the proliferation of human lung carcinoma cells, A549 and human leukemic cells, K562. DW2282 effectively inhibited cancer cell proliferation in vitro. Colony forming assay and viability tests demonstrated that DW2282 is a cytotoxic agent rather than a cytostatic agent. The isotope uptake test exhibited that DW2282 inhibited or inactivated protein synthesis. Also, under conditions which cause RNA or protein synthesis inhibition, by co-treatment with actinomycin D or cycloheximide, reduced the anticancer effects of DW2282. This means that the cytotoxicity of DW2282 depends partially on RNA or protein synthesis and proteins affected by DW2282 may inactivate or alter the process of the synthesis of another protein. DW2282 activity was highly diminished in the presence of colcemid, a metaphase spindle blocker. This result suggests that DW2282 may be related to the cell cycle. After exposure to DW2282, morphologically apoptotic cells appeared in A549 cells and fragmented DNA was detected in K562 cells. It demonstrated that apoptosis is one of the mechanisms by which DW2282 inhibits the proliferation of A549 and K562 cells.
Hwang
H S
HS
Central Research Laboratories, Dong Wha Pharm. Ind. Co., Ltd., Anyang, Kyunggi-Do, Korea. hhyunsook@hotmail.com
Moon
E Y
EY
Seong
S K
SK
Choi
C H
CH
Chung
Y H
YH
Jung
S H
SH
Lee
D K
DK
Yoon
S J
SJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000096:biosynthesis; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012334:RNA, Neoplasm / Q000096:biosynthesis; D013450:Sulfones / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D007093:Imidazoles; D009363:Neoplasm Proteins; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D012334:RNA, Neoplasm; D013450:Sulfones; C404303:DW 2282