L-Se-methylselenocysteine sensitizes lung carcinoma to chemotherapy

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.

Automated summary

The organic selenium compound SeMC showed high sensitivity in inhibiting A549 lung adenocarcinoma cells, inducing synergistic lethality when combined with chemotherapeutics. SeMC promoted lipid peroxidation and increased ROS generation in cancer cells. The in vivo efficacy of combination therapy was significantly enhanced by hydrogel-mediated drug delivery.