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In vitro antitumor activity of TAS-103 against freshly-isolated human colorectal cancer
T Tsunoda1, H Tanimura, H Yamaue
1Department of Surgery and Bioengineering, Advanced Clinical Research Center, Institute of Medical Science, The University of Tokyo, Japan. tsunodat@ims.u-tokyo.ac.jp
Abstract:
DNA topoisomerases (Topo) are enzymes that relieve the secondary twist on the DNA strand in the process of DNA synthesis and transcription; therefore they are unique targeting molecules for the chemotherapy of colorectal cancer. TAS-103 (6-[[2-(dimethylamino)ethyl]amino]-3-hydroxy-7H-in-deno [2,1-c]quinolin-7-one dihydrochloride, MW; 406.31), a novel quinoline derivative, has recently been established as a Topo I and Topo II inhibitor. The aim of the present study was to investigate the antitumor activity of TAS-103 by the MTT assay in human highly-purified and freshly-isolated colorectal cancer cells. To our knowledge, this is the first data concerning the antitumor activity of TAS-103 in highly-purified and isolated human colorectal cancer cells. TAS-103 showed the strongest antitumor activity among the conventional anticancer agents for colorectal cancer (p<0.05). The combination with CDDP augmented the antitumor activity of TAS-103 (p<0.05), indicating that CDDP is one of the most potent candidates to be used in combination with TAS-103. To predict the clinical effect of TAS-103, the expressions of Topo I and Topo II were measured by quantitative PCR. However, a correlation between the expression of Topo and the antitumor activity of TAS-103 was not established. In conclusion, according to this data, TAS-103 may be useful in the chemotherapy of colorectal cancer.
Insights
The novel quinoline derivative TAS-103 demonstrated superior antitumor activity against colorectal cancer cells compared to existing treatments. Combining TAS-103 with CDDP further enhanced its efficacy, suggesting potential for improved chemotherapy regimens.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- DNA topoisomerases (Topo) are crucial enzymes in DNA replication and transcription.
- Targeting Topo I and Topo II offers a promising strategy for colorectal cancer chemotherapy.
- TAS-103 is a novel quinoline derivative identified as a Topo I and Topo II inhibitor.
Purpose of the Study:
- To evaluate the in vitro antitumor activity of TAS-103 in highly-purified human colorectal cancer cells.
- To assess the potential synergistic effect of TAS-103 in combination with CDDP.
- To explore the correlation between Topo I/II expression and TAS-103 efficacy.
Main Methods:
- MTT assay was employed to determine the antitumor activity of TAS-103.
- Quantitative PCR was used to measure Topo I and Topo II expression levels.
- Human highly-purified and freshly-isolated colorectal cancer cells were utilized.
Main Results:
- TAS-103 exhibited significantly stronger antitumor activity than conventional colorectal cancer agents (p<0.05).
- Combination therapy with CDDP notably augmented TAS-103's antitumor effects (p<0.05).
- No significant correlation was found between Topo I/II expression and TAS-103's antitumor activity.
Conclusions:
- TAS-103 shows significant potential as a novel chemotherapeutic agent for colorectal cancer.
- CDDP is a strong candidate for combination therapy with TAS-103.
- Further clinical studies are warranted to validate TAS-103's efficacy in colorectal cancer treatment.