A New Water-soluble Camptothecin Derivative, DX-8951f, Exhibits Potent Antitumor Activity against Human Tumorsin vitroandin vivo
| Autor: | Masamichi Sugimori, Satoru Ohsuki, Yasuhide Hirota, Eiji Kumazawa, Masashi Aonuma, Kouichi Uoto, Hirofumi Terasawa, Akio Ejima, Ikuo Mitsui, Keiki Sato |
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| Rok vydání: | 1995 |
| Předmět: |
Male
Cancer Research Transplantation Heterologous Mice Nude Antineoplastic Agents P‐Glycoprotein Article Mice chemistry.chemical_compound In vivo Neoplasms Tumor Cells Cultured medicine Animals Humans Enzyme Inhibitors Exatecan Mice Inbred BALB C CPT‐11 biology Topoisomerase Water Cancer Exatecan mesylate Biological activity medicine.disease Topoisomerase I Solubility Oncology Biochemistry chemistry biology.protein Cancer research Camptothecin Topotecan Drug Screening Assays Antitumor Topoisomerase I Inhibitors Neoplasm Transplantation medicine.drug |
| Zdroj: | Japanese Journal of Cancer Research : Gann |
| ISSN: | 0910-5050 |
| Popis: | CPT‐11, a semisynthetic derivative of camptothecin, exhibited strong antitumor activity against lymphoma, lung cancer, colorectal cancer, gastric cancer, ovarian cancer, and cervical cancer. CPT‐11 is a pro‐drug that is converted to an active metabolite, SN‐38, in vivo by enzymes such as carboxylesterase. We synthesized a water‐soluble and non‐pro‐drug analog of camptothecin, DX‐8951f. It showed both high in vitro potency against a series of 32 malignant cell lines and significant topoisomerase I inhibition. The anti‐proliferative activity of DX‐8951f, as indicated by the mean GI50 value, was about 6 and 28 times greater than that of SN‐38 or SK&F 10486‐A (Topotecan), respectively. These three derivatives of camptothecin showed similar patterns of differential response among 32 cell lines, that is, their spectra of in vitro cytotoxicity were almost the same. The antitumor activity of three doses of DX‐8951f administered i.v. at 4‐day intervals against human gastric adenocarcinoma SC‐6 xenografts was greater than that of CPT‐11 or SK&F 10486‐A. Moreover, it overcame P‐glycoprotein‐mediated multi‐drug resistance. These data suggest that DX‐8951f has a high antitumor activity and is a potential therapeutic agent. |
| Databáze: | OpenAIRE |
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