Distamycin A enhances the cytotoxicity of duocarmycin A and suppresses duocarmycin A-induced apoptosis in human lung carcinoma cells

Hirota, Mikako; Fujiwara, Tsuyoshi; Mineshita, Satoru; Sugiyama, Hiroshi; Teraoka, Hirobumi

doi:10.1016/j.biocel.2007.01.019

Cited by 6 publications

(4 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27, 35 The DNA damage results in cleavage of full-length caspase-9, subsequent activation of caspase-3 and, ultimately, cell death. 25, 26 As shown in Figure 2, apoptosis induction via the intrinsic pathway was confirmed by the detection of cleaved PARP, cleaved caspase-3 and the full-length caspase-8, as well as the decrease of full-length caspase-3 and -9, in cells treated with a mixture of prodrug and purified β-galactosidase.…”

Section: Discussionmentioning

confidence: 70%

See 1 more Smart Citation

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA

et al. 2010

View full text Add to dashboard Cite

Breast cancer is the most common cause of cancer-related death worldwide, thus remaining a crucial health problem among women despite advances in conventional therapy. Therefore, new alternative strategies are needed for effective diagnosis and treatment. One approach is the use of oncolytic viruses for gene-directed enzyme prodrug therapy. Here, the lacZ-carrying vaccinia virus (VACV) strain GLV-1h68 was used in combination with a β-galactosidase-activatable prodrug derived from a seco-analog of the natural antibiotic duocarmycin SA. Tumor cell infection with the VACV strain GLV-1h68 led to production of β-galactosidase, essential for the conversion of the prodrug to the toxic compound. Furthermore, drug-dependent cell kill and induction of the intrinsic apoptosis pathway in tumor cells was also observed on combination therapy using the prodrug and the GLV-1h68 strain, despite the fact that VACV strains encode antiapoptotic proteins. Moreover, GI-101A breast cancer xenografts were effectively treated by the combination therapy. In conclusion, the combination of a β-galactosidase-activatable prodrug with a tumor-specific vaccinica virus strain encoding this enzyme, induced apoptosis in cultures of the human GI-101A breast cancer cells, in which a synergistic oncolytic effect was observed. Moreover, in vivo, additional prodrug treatment had beneficial effects on tumor regression in GLV-1h68-treated GI-101A-xenografted mice.

show abstract

Section: Discussionmentioning

confidence: 70%

“…However, studies have not yet determined whether target cell death also occurred via the same intrinsic apoptosis mechanism as already described for duocarmycin SA. 25, 26, 27 …”

Section: Resultsmentioning

confidence: 99%

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA

et al. 2010

View full text Add to dashboard Cite

show abstract

“…Distamycin A, the natural product that provided the structural inspiration for Py-Im polyamides, inhibits the initiation of RNA synthesis in cell-free assays (27). In cell culture, distamycin also induces degradation of RPB1 and activates p53 (31,32). However, low antitumor potency and poor stability limit its utility.…”

Section: Resultsmentioning

confidence: 99%

Antitumor activity of a pyrrole-imidazole polyamide

Yang

Nickols

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

113

132

View full text Add to dashboard Cite

Many cancer therapeutics target DNA and exert cytotoxicity through the induction of DNA damage and inhibition of transcription. We report that a DNA minor groove binding hairpin pyrroleimidazole (Py-Im) polyamide interferes with RNA polymerase II (RNAP2) activity in cell culture. Polyamide treatment activates p53 signaling in LNCaP prostate cancer cells without detectable DNA damage. Genome-wide mapping of RNAP2 binding shows reduction of occupancy, preferentially at transcription start sites, but occupancy at enhancer sites is unchanged. Polyamide treatment results in a time-and dose-dependent depletion of the RNAP2 large subunit RPB1 that is preventable with proteasome inhibition. This polyamide demonstrates antitumor activity in a prostate tumor xenograft model with limited host toxicity.minor groove binder | small molecule transcription inhibitor | ChIP-Seq

show abstract

“…They can be used in combination with other drugs for cytotoxic enhancement with an aim to reduce the applied drug concentrations. For example, distamycin A in combination with duocarmycin A enhanced the cytotoxicity of duocarmycin A by 10 times in comparison with duocarmycin A alone (52).…”

Section: Dna Groove Bindersmentioning

confidence: 99%

Antineoplastic DNA-Binding Compounds: Intercalating and Minor Groove Binding Drugs

Mišković

Bujak

Lončar

et al. 2013

Archives of Industrial Hygiene and Toxicology

View full text Add to dashboard Cite

DNA intercalating and minor groove binding compounds are new weapons in the battle against malignant diseases. These antineoplastic agents target the DNA molecule and interfere with the cell cycle leading to rapidly proliferating cell death. They are mainly derivates of a naturally occurring organic compound derived from a microorganism or plant. Intercalators usually act as topoisomerase I and/or II poisons, while the mechanisms of DNA minor groove binders are a combination of several steps including topoisomerase poisoning. This paper gives an overview of some of the developed DNA intercalating and minor groove binding compounds, as well as an explanation of their chemical structures, origins, and application in chemotherapy.

show abstract

Distamycin A enhances the cytotoxicity of duocarmycin A and suppresses duocarmycin A-induced apoptosis in human lung carcinoma cells

Cited by 6 publications

References 32 publications

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA

Enhanced tumor therapy using vaccinia virus strain GLV-1h68 in combination with a β-galactosidase-activatable prodrug seco-analog of duocarmycin SA

Antitumor activity of a pyrrole-imidazole polyamide

Antineoplastic DNA-Binding Compounds: Intercalating and Minor Groove Binding Drugs

Contact Info

Product

Resources

About