Luteolin reduces cancer‑induced skeletal and cardiac muscle atrophy in a Lewis lung cancer mouse model

Abstract

Luteolin was recently demonstrated to suppress tumor growth by interfering with nuclear factor (NF)‑κB activation. As the NF‑κB pathway plays a critical role in muscular atrophy associated with cancer cachexia, we aimed to investigate the potential of luteolin to alleviate cancer‑associated cachexia in a Lewis lung cancer mouse model. C57BL/6 mice were divided into three groups: A control group, a model group and a luteolin group. Mice in the model and luteolin groups received a subcutaneous injection of Lewis lung cancer cells, while the control group received PBS. Subsequently, the tumor mass, serum, gastrocnemius muscle and heart were collected on day 21. The serum, gastrocnemius muscle and heart were weighed and prepared for use in enzyme‑linked immunosorbent assay (ELISA), western blotting (WB) and quantitative reverse transcription polymerase chain reaction (qRT‑PCR) analyses. The results revealed that the tumor‑free body mass was significantly reduced in tumor‑bearing mice compared with that of mice in the other groups. The gastrocnemius muscle mass and heart mass were greater in the luteolin treatment group than in the control group. Tumor necrosis factor (TNF)‑α and interleukin (IL)‑6 levels were lower in the luteolin treatment group than in the model group. In addition, according to the results of the WB and qRT‑PCR analyses, the expression of the E3 ubiquitin ligase muscle RING finger‑containing protein 1 (MuRF1) was downregulated in skeletal muscle and cardiac muscle, whereas atrogin‑1 was downregulated only in skeletal muscle in the luteolin treatment group vs. the model group. Furthermore, IκB kinase β (IKKβ) and phospho‑p65 were significantly downregulated in skeletal muscle and cardiac tissue, whereas the expression of p‑p38 was downregulated only in skeletal muscle in the luteolin treatment group when compared with their expression levels in the model group, as determined by the WB analysis. In conclusion, from the current results, we conclude that luteolin is able to reduce inflammatory burden, downregulate the expression of genes associated with muscle protein breakdown, and protect skeletal and heart muscle from cancer‑induced wasting and loss in vivo. Therefore, luteolin has the potential to be developed into a novel anti‑cachetic agent.

Chrysanthemi Zawadskii var. Latilobum Attenuates Obesity-Induced Skeletal Muscle Atrophy via Regulation of PRMTs in Skeletal Muscle of Mice

“…Interestingly, our results showed that linarin and luteolin decreased mRNA levels of atrophic genes in PA-treated C2C12 cells. This was consistent with a previous report that luteolin inhibits the expression of MuRF1 and Atrogin at both the transcriptional and translational levels in skeletal muscle of a cancer-induced skeletal and cardiac muscle atrophy model [49]. Pretreatment with luteolin significantly prevents the decrease in C2C12 myotube diameter caused by LPS stimulation [50].…”

Luteolin inhibits cell cycle progression and induces apoptosis of breast cancer cells through downregulation of human telomerase reverse transcriptase

“…5A-C). NF-κB signaling is one of the major upstream targets of c-Myc and a number of studies have demonstrated that luteolin targets NF-κB (23–25). NF-κB normally binds to IκBα and is localized in the cytoplasm.…”

Flavonoids: nutraceutical potential for counteracting muscle atrophy

“…This finding indicates that the phenyl ring in luteolin is essential for regulating atrogin-1 in LPS-treated C2C12 myotubes. Two studies have investigated the molecular mechanisms of luteolin-induced inhibition of muscle atrophy in different animal models: a LLC tumor-bearing mouse model for cachexia (Chen et al, 2018b) and a dexamethasone-treated mouse (Hawila et al, 2019). In the cachexia model, luteolin increased the weight of the gastrocnemius muscle, tibialis anterior muscle, and heart (Chen et al, 2018b).…”