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

S Cao; F A Durrani; K Tóth; Y M Rustum

doi:10.1038/bjc.2014.85

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

Journal article

Open access

Peer reviewed

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

S Cao, F A Durrani, K Tóth and Y M Rustum

British journal of cancer, Vol.110(7), pp.1733-1743

04/02/2014

DOI: 10.1038/bjc.2014.85

PMCID: PMC3974093

PMID: 24619073

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Abstract

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. 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. 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. 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.

Animals

Antineoplastic Combined Chemotherapy Protocols - adverse effects

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Camptothecin - administration & dosage

Camptothecin - adverse effects

Camptothecin - analogs & derivatives

Cisplatin - administration & dosage

Cisplatin - adverse effects

Cyclophosphamide - administration & dosage

Cyclophosphamide - adverse effects

Cytoprotection

Female

Humans

Mice

Mice, Nude

Neoplasms - drug therapy

Neoplasms - pathology

Organoplatinum Compounds - administration & dosage

Organoplatinum Compounds - adverse effects

Rats

Rats, Inbred F344

Selenocysteine - administration & dosage

Selenocysteine - analogs & derivatives

Tumor Cells, Cultured

Xenograft Model Antitumor Assays

Details

Title: Subtitle: Se-methylselenocysteine offers selective protection against toxicity and potentiates the antitumour activity of anticancer drugs in preclinical animal models
Creators: S Cao - Roswell Park Cancer Institute
F A Durrani - Roswell Park Cancer Institute
K Tóth - Roswell Park Cancer Institute
Y M Rustum - Roswell Park Cancer Institute
Resource Type: Journal article
Publication Details: British journal of cancer, Vol.110(7), pp.1733-1743
DOI: 10.1038/bjc.2014.85
PMID: 24619073
PMCID: PMC3974093
ISSN: 0007-0920
eISSN: 1532-1827
Grant note: P30 CA016056 / NCI NIH HHS CA16056 / NCI NIH HHS
Language: English
Date published: 04/02/2014
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359589602771

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