L-Se-methylselenocysteine sensitizes lung carcinoma to chemotherapy.

Abstract

OBJECTIVES:

Organic Selenium (Se) compounds such as L-Se-methylselenocysteine (L-SeMC/SeMC) have been employed as a class of anti-oxidant to protect normal tissues and organs from chemotherapy-induced systemic toxicity. However, their comprehensive effects on cancer cell proliferation and tumour progression remain elusive.

MATERIALS AND METHODS:

CCK-8 assays were conducted to determine the viabilities of cancer cells after exposure to SeMC, chemotherapeutics or combined treatment. Intracellular reactive oxygen species (ROS) levels and lipid peroxidation levels were assessed via fluorescence staining. The efficacy of free drugs or drug-loaded hydrogel against tumour growth was evaluated in a xenograft mouse model.

RESULTS:

Among tested cancer cells and normal cells, the A549 lung adenocarcinoma cells showed higher sensitivity to SeMC exposure. In addition, combined treatments with several types of chemotherapeutics induced synergistic lethality. SeMC promoted lipid peroxidation in A549 cells and thereby increased ROS generation. Significantly, the in vivo efficacy of combination therapy was largely potentiated by hydrogel-mediate drug delivery.

CONCLUSIONS:

Our study reveals the selectivity of SeMC in the inhibition of cancer cell proliferation and develops an efficient strategy for local combination therapy.

• Authors: Jia Ma, Jing Huang, Jinli Sun, Yanfeng Zhou, Xiaoyuan Ji, Daoxia Guo, Chang Liu, Jiyu Li, Jiye Zhang, Haiyun Song
• Journal: Cell proliferation (Cell Prolif) Vol. 54 Issue 5 Pg. e13038 (May 2021) ISSN: 1365-2184 [Electronic] England
• PMID: 33793020 (Publication Type: Journal Article)
• Copyright: © 2021 The Authors. Cell Proliferation Published by John Wiley & Sons Ltd.

Chemical References

• Antineoplastic Agents
• Drug Carriers
• Hydrogels
• Reactive Oxygen Species
• Selenocysteine
• selenomethylselenocysteine

Topics

• Animals
• Antineoplastic Agents (chemistry, pharmacology, therapeutic use)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Drug Carriers (chemistry)
• Female
• Humans
• Hydrogels (chemistry)
• Lipid Peroxidation (drug effects)
• Lung Neoplasms (drug therapy, metabolism, pathology)
• Mice
• Mice, Nude
• Reactive Oxygen Species (metabolism)
• Selenocysteine (analogs & derivatives, chemistry, pharmacology, therapeutic use)
• Xenograft Model Antitumor Assays