Abstract
Background Curcumin is a polyphenol plant-derived compound with anti-inflammatory, antioxidant stress, and anticancer properties that make it have the potential to treat cancer cachexia. However, the role of it in breast cancer cachexia remains unclear. Methods The 4T1 cells were subcutaneously injected into BALB/c mice to induce breast cancer cachexia. After tumor formation, the animals were divided into groups and given curcumin or saline interventions. The therapeutic effect of curcumin on breast cancer cachexia was characterized by tumor growth, changes in body mass and gastrocnemius mass, muscle function test, histopathology, and serum nutrition indexes. Mitochondrial function in muscle tissue was observed by transmission electron microscopy and ATP detection, muscle inflammatory factors were detected by ELISA, muscle differential metabolites were detected by 1HNMR metabolomics, and the muscle tissue ubiquitination levels and NF-KB expression were also analyzed by RT-qPCR and Western blot. Results Dynamic in vivo bioluminescence imaging find that curcumin inhibited the growth of tumor in triple-negative breast cancer- (TNBC-) bearing mice, slowed down the loss of body weight and gastrocnemius weight, corrected the mitochondrial dysfunction and malnutrition status, and also significantly improved skeletal muscle function. ELISA analysis found that the level of inflammatory factors in muscle tissue was reduced. 1HNMR metabolomics analysis suggested that curcumin could regulate energy metabolism pathways. RT-qPCR and Western blot analysis found that the expression of myogenic factor myogenin was increased and the expression of myodegradation factor myostatin was decreased in the gastrocnemius; the level of ubiquitination and activation of the NF-κB pathway were also declined. Conclusions Curcumin reduces ubiquitination, inflammation in skeletal muscle by regulating the NF-KB/UPS axis and improves muscle malignant metabolic phenotype and mitochondrial dysfunction, to alleviate muscle atrophy and loss of function in mice with breast cancer cachexia.
Highlights
We find that curcumin inhibited the growth of tumors and corrects mitochondrial dysfunction and malnutrition status in muscle fibers, as well as skeletal muscle function significant improvement
We measured the levels of inflammatory cytokines TNF-α and IL-6 in gastrocnemius tissue; the results indicated that the increased levels of TNFα and IL-6 levels in the model group were significantly decreased by curcumin administration (Figures 7(a) and 7(b); p = 0:0006, p = 0:016)
Except for the observed mitochondrial dysfunction in model mouse gastrocnemius muscles, the adenosine triphosphate (ATP) content in the model mice was decreased, but it was partly recovered in the curcumin group. These results indicated that the mitochondrial function of muscle fibers in mice treated with curcumin was improved, which brought about an increase in ATP production
Summary
Breast cancer is the most common female tumor disease; its morbidity and mortality rates are increasing year by year, resulting in a serious social and economic burden. Weight loss and skeletal muscle atrophy are common features of cachexia in cancer patients and are independent prognostic factors for poor clinical outcomes [6]. The therapeutic effect of curcumin on breast cancer cachexia was characterized by tumor growth, changes in body mass and gastrocnemius mass, muscle function test, histopathology, and serum nutrition indexes. Dynamic in vivo bioluminescence imaging find that curcumin inhibited the growth of tumor in triple-negative breast cancer- (TNBC-) bearing mice, slowed down the loss of body weight and gastrocnemius weight, corrected the mitochondrial dysfunction and malnutrition status, and significantly improved skeletal muscle function. Inflammation in skeletal muscle by regulating the NF-KB/UPS axis and improves muscle malignant metabolic phenotype and mitochondrial dysfunction, to alleviate muscle atrophy and loss of function in mice with breast cancer cachexia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
