Your browser doesn't support javascript.
loading
A Low-Toxicity DNA-Alkylating N-Mustard-Quinoline Conjugate with Preferential Sequence Specificity Exerts Potent Antitumor Activity Against Colorectal Cancer.
Chen, Tai-Lin; Lin, Yi-Wen; Chen, Yan-Bo; Lin, Jing-Jer; Su, Tsann-Long; Shen, Chia-Ning; Lee, Te-Chang.
Afiliación
  • Chen TL; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan; Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
  • Lin YW; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
  • Chen YB; Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan.
  • Lin JJ; Institute of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, Taipei 10051, Taiwan.
  • Su TL; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan.
  • Shen CN; Institute of Biochemistry and Molecular Biology, National Yang-Ming University, Taipei 11221, Taiwan; Genomics Research Center, Academia Sinica, Taipei 11529, Taiwan. Electronic address: cnshen@gate.sinica.edu.tw.
  • Lee TC; Institute of Biomedical Sciences, Academia Sinica, Taipei 11529, Taiwan; Institute of Pharmacology, National Yang-Ming University, Taipei 11221, Taiwan. Electronic address: bmtcl@ibms.sinica.edu.tw.
Neoplasia ; 20(2): 119-130, 2018 02.
Article en En | MEDLINE | ID: mdl-29247884
Efficacy and safety are fundamental prerequisites for anticancer drug development. In the present study, we explored the anti-colorectal cancer (CRC) activity of SL-1, a DNA-directed N-mustard-quinoline conjugate. The N-mustard moiety in SL-1 induced DNA strand breaks, interstrand cross-links (ICLs), G2/M arrest, and apoptosis, whereas its quinoline moiety preferentially directed SL-1 to target the selective guanine sequence 5'-G-G/C-N-G-C/T-3'. Notably, SL-1 was highly cytotoxic to various CRC cell lines. Experiments using xenograft models revealed that SL-1 was more potent than 5-fluorouracil (5-FU) and oxaliplatin for suppressing the growth of RKO and RKO-E6 (oxaliplatin-resistant subline) cells as well as metastatic SW620 cells. In addition, SL-1 combined with 5-FU was more effective than oxaliplatin and 5-FU for suppressing RKO or SW620 cell growth in mice. Significantly, compared with cisplatin, oxaliplatin, or 5-FU, SL-1 alone or in combination with 5-FU did not cause obvious kidney or liver toxicity in ICR mice. In summary, SL-1, a DNA-directed alkylating agent, is established as an anti-CRC agent with high efficacy and low toxicity and thus warrants further development for the treatment of CRC patients.
Asunto(s)

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Quinolinas / Compuestos de Mostaza / ADN / Neoplasias Colorrectales / Antineoplásicos Alquilantes / Antineoplásicos Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article

Texto completo: 1 Base de datos: MEDLINE Asunto principal: Quinolinas / Compuestos de Mostaza / ADN / Neoplasias Colorrectales / Antineoplásicos Alquilantes / Antineoplásicos Idioma: En Revista: Neoplasia Asunto de la revista: NEOPLASIAS Año: 2018 Tipo del documento: Article