1. Academic Validation
  2. Se-methylselenocysteine offers selective protection against toxicity and potentiates the antitumour activity of anticancer drugs in preclinical animal models

Se-methylselenocysteine offers selective protection against toxicity and potentiates the antitumour activity of anticancer drugs in preclinical animal models

  • Br J Cancer. 2014 Apr 2;110(7):1733-43. doi: 10.1038/bjc.2014.85.
S Cao 1 F A Durrani 2 K Tóth 2 Y M Rustum 2
Affiliations

Affiliations

  • 1 Department of Medicine, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
  • 2 Department of Cancer Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Abstract

Background: Identification and development of drugs that can effectively modulate the therapeutic efficacy and toxicity of chemotherapy remain an unmet challenge. We evaluated the effects of Se-methylselenocysteine (MSC) on the toxicity and antitumour activity of cyclophosphamide, cisplatin, oxaliplatin, and irinotecan in animal models.

Methods: Cyclophosphamide, cisplatin, and oxaliplatin were administered by a single i.v. injection and irinotecan by i.v. weekly × 4 schedules. For the combination, MSC was administered daily via the oral route for 7 days in mice and daily for 14 days in rats before and concurrent with drug administration.

Results: Se-methylselenocysteine significantly protected against organ-specific toxicity induced by lethal doses of cyclophosphamide, cisplatin, oxaliplatin, and irinotecan. These include diarrhoea, stomatitis, alopecia, bladder, kidney, and bone marrow toxicities. Protection from lethal toxicity by MSC was associated with enhanced antitumour activity in rats bearing advanced Ward colorectal carcinoma and in nude mice bearing human squamous cell carcinoma of the head and neck, FaDu, and A253 xenografts.

Conclusions: Se-methylselenocysteine offers selective protection against organ-specific toxicity induced by clinically active agents and enhances further antitumour activity, resulting in improved therapeutic index. These data provided the rationale for the need to clinically evaluate MSC as selective modulator of the antitumour activity and selectivity of Anticancer drugs.

Figures
Products
我们的 Cookie 政策

我们使用 Cookies 和类似技术以提高网站的性能和提升您的浏览体验,部分功能也使用 Cookies 帮助我们更好地理解您的需求,为您提供相关的服务。 如果您有任何关于我们如何处理您个人信息的疑问,请阅读我们的《隐私声明》