In vitro enhancement of antitumor activity of a water-soluble duocarmycin derivative, KW-2189, by caffeine-mediated DNA-repair inhibition in human lung cancer cells

Japanese Journal of Cancer Research : Gann
H OgasawaraN Saijo

Abstract

Duocarmycins, including KW-2189, bind in the minor groove of double-stranded DNA at A-T-rich sequences, followed by covalent bonding with N-3 of adenine in preferred sequences. We examined the effect of DNA-repair modulators, such as caffeine and aphidicolin, on the cytotoxicity of duocarmycins towards human lung cancer cells, as determined by dye formation assay. Caffeine (0.5 or 1 mM), but not aphidicolin, enhanced the growth-inhibitory activity of KW-2189, DU-86, and duocarmycin SA. Caffeine inhibited repair of DNA strand breaks induced by KW-2189, as assayed by the alkaline elution technique. This suggests that duocarmycin-induced DNA strand breaks, which are potentially lethal to cells, are repaired through a caffeine-sensitive pathway.

References

Nov 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·D E SzymkowskiR D Wood
Jan 1, 1992·Japanese Journal of Cancer Research : Gann·K GomiT Hirata
Jan 1, 1989·Japanese Journal of Cancer Research : Gann·K Tomita, H Tsuchiya

❮ Previous
Next ❯

Citations

Aug 8, 2013·Expert Opinion on Pharmacotherapy·Norio Yamamoto, Hiroyuki Tsuchiya
Dec 30, 2003·International Journal of Cancer. Journal International Du Cancer·Fumiko TaguchiKazuto Nishio
Jun 1, 2002·American Journal of Clinical Oncology·Svetomir N MarkovicEdward T Creagan

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.