9-amino Camptothecin is a potent, water-insoluble topoisomerase I inhibitor with antitumor activity[1]. Topoisomerase I regulates DNA topology through a relaxation-annealing mechanism and participates in key nuclear processes such as DNA replication, transcription, and repair without requiring ATP[2]. 9-amino Camptothecin induces apoptosis and DNA damage and is commonly used in the treatment and research of ovarian cancer, lymphoma, and colorectal cancer[3,4,5].
In vitro, treatment of human breast cancer MCF-7, bladder cancer MGH-U1, and colon cancer HT-29 cells with 9-amino Camptothecin (0.27-274nM) for 4-240h resulted in cytotoxicity that increased with both drug concentration and exposure time. Following treatment with 9-amino Camptothecin (137nM) for 24h, all MCF-7, MGH-U1, and HT-29 cells exhibited S-phase accumulation[6]. Treatment of human prostate cancer PC-3, PC-3M, LNCaP, and DU145 cell lines with 9-amino Camptothecin (1-500nM) for 96h inhibited cell viability in a time- and concentration-dependent manner, with IC50 values of 34.1nM, 10nM, 8.9nM, and 6.5nM, respectively[7].
In vivo, 9-amino Camptothecin (0.35, 0.75, and 1mg/kg/day; 5 days/week; 3 weeks) was administered by oral gavage to nude mice bearing PC-3 xenografts. The 0.35mg/kg/day dose completely inhibited tumor growth, while the 0.75 and 1mg/kg/day doses both resulted in tumor volume reduction[7].
References:
[1] TANIZAWA A, FUJIMORI A, FUJIMORI Y, et al. Comparison of topoisomerase I inhibition, DNA damage, and cytotoxicity of camptothecin derivatives presently in clinical trials[J]. Journal of the National Cancer Institute, 1994, 86(11): 836-842.
[2] POMMIER Y, POURQUIER P, FAN Y I, et al. Mechanism of action of eukaryotic DNA topoisomerase I and drugs targeted to the enzyme[J]. Biochimica et Biophysica Acta (BBA)-Gene Structure and Expression, 1998, 1400(1-3): 83-106.
[3] HUANG G E, WANG H, YANG L X. Enhancement of radiation-induced DNA damage and inhibition of its repair by a novel camptothecin analog[J]. Anticancer Research, 2010, 30(3): 937-944.
[4] TAKIMOTO C H, THOMAS R. The clinical development of 9-aminocamptothecin[J]. Annals of the New York Academy of Sciences, 2000, 922(1): 224-236.
[5] HOCHSTER H, PLIMACK E R, RUNOWICZ C D, et al. Biweekly 72-hour 9-aminocamptothecin infusion as second-line therapy for ovarian carcinoma: phase II study of the New York Gynecologic Oncology Group and the Eastern Cooperative Oncology Group[J]. Journal of Clinical Oncology, 2004, 22(1): 120-126.
[6] LI M L, HORN L, FIRBY P S, et al. Pharmacological determinants of 9-aminocamptothecin cytotoxicity[J]. Clinical Cancer Research, 2001, 7(1): 168-174.
[7] DE SOUZA P L, COOPER M R, IMONDI A R, et al. 9-Aminocamptothecin: a topoisomerase I inhibitor with preclinical activity in prostate cancer[J]. Clinical cancer research: an official journal of the American Association for Cancer Research, 1997, 3(2): 287-294.
9-amino Camptothecin是一种强效、不溶于水且具有抗肿瘤活性的拓扑异构酶I抑制剂[1]。拓扑异构酶I通过松弛-退火机制调节DNA拓扑结构，无需ATP即可参与DNA复制、转录和修复等关键核内过程[2]。9-amino Camptothecin能诱导细胞凋亡和DNA损伤，通常用于卵巢癌、淋巴癌和结直肠癌的治疗和研究[3,4,5]。
在体外，9-amino Camptothecin（0.27-274nM）处理人乳腺癌MCF-7、膀胱癌MGH-U1和结肠癌HT-29细胞4-240h，细胞毒性随药物浓度和暴露时间的增加而增强。9-amino Camptothecin（137nM）处理MCF-7、MGH-U1和HT-29细胞24h，所有细胞均出现S期积累[6]。9-amino Camptothecin（1-500nM） 处理人前列腺癌 PC-3、PC-3M、LNCaP和DU145细胞系96 h，细胞活力呈时间和浓度依赖性抑制，IC50值分别为 34.1nM、10nM、8.9nM 和6.5nM[7]。
在体内，9-amino Camptothecin（0.35, 0.75, and 1mg/kg/day; 5 days/week; 3 weeks）通过口服灌胃治疗携带PC-3异种移植瘤的裸鼠，0.35mg/kg/day剂量可完全抑制肿瘤生长，0.75和1mg/kg/day剂量均可使肿瘤体积缩小[7]。