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Updated: Dec 13, 2025
The Colon-26 Carcinoma Tumor-bearing Mouse as a Model for the Study of Cancer Cachexia
Published on: November 30, 2016
Withaferin A attenuates ovarian cancer-induced cardiac cachexia
Natia Q Kelm1, Alex R Straughn1, Sham S Kakar1,2
1James Graham Brown Cancer Center, University of Louisville, Louisville, KY, United States of America.
Abstract:
Cachexia is a common multifactorial syndrome in the advanced stages of cancer and accounts for approximately 20-30% of all cancer-related fatalities. In addition to the progressive loss of skeletal muscle mass, cancer results in impairments in cardiac function. We recently demonstrated that WFA attenuates the cachectic skeletal muscle phenotype induced by ovarian cancer. The purpose of this study was to investigate whether ovarian cancer induces cardiac cachexia, the possible pathway involved, and whether WFA attenuates cardiac cachexia. Xenografting of ovarian cancer induced cardiac cachexia, leading to the loss of normal heart functions. Treatment with WFA rescued the heart weight. Further, ovarian cancer induced systolic dysfunction and diastolic dysfunction Treatment with WFA preserved systolic function in tumor-bearing mice, but diastolic dysfunction was partially improved. In addition, WFA abrogated the ovarian cancer-induced reduction in cardiomyocyte cross-sectional area. Finally, treatment with WFA ameliorated fibrotic deposition in the hearts of tumor-bearing animals. We observed a tumor-induced MHC isoform switching from the adult MHCα to the embryonic MHCβ isoform, which was prevented by WFA treatment. Circulating Ang II level was increased significantly in the tumor-bearing, which was lowered by WFA treatment. Our results clearly demonstrated the induction of cardiac cachexia in response to ovarian tumors in female NSG mice. Further, we observed induction of proinflammatory markers through the AT1R pathway, which was ameliorated by WFA, in addition to amelioration of the cachectic phenotype, suggesting WFA as a potential therapeutic agent for cardiac cachexia in oncological paradigms.
Insights
Ovarian cancer causes cardiac cachexia, leading to heart dysfunction. WFA treatment improved heart function and reduced inflammation, suggesting its potential as a therapeutic agent for cancer-related cardiac cachexia.
Area of Science:
- Oncology
- Cardiology
- Biochemistry
Background:
- Cachexia is a multifactorial syndrome common in advanced cancer, causing significant mortality.
- Cancer cachexia involves skeletal muscle loss and cardiac dysfunction.
- Previous studies showed WFA attenuates skeletal muscle cachexia in ovarian cancer models.
Purpose of the Study:
- To investigate if ovarian cancer induces cardiac cachexia.
- To identify the underlying pathways involved in cancer-induced cardiac dysfunction.
- To determine if WFA can attenuate cardiac cachexia in ovarian cancer.
Main Methods:
- Ovarian cancer xenograft model in female NSG mice.
- Assessment of cardiac function (systolic and diastolic).
- Histological analysis of cardiac tissue (cardiomyocyte size, fibrosis).
- Analysis of MHC isoform expression and Angiotensin II (Ang II) levels.
Main Results:
- Ovarian cancer induced cardiac cachexia, characterized by reduced heart weight and impaired cardiac function.
- WFA treatment preserved heart weight, improved systolic function, and partially improved diastolic dysfunction.
- WFA abrogated cardiomyocyte atrophy, reduced cardiac fibrosis, and prevented MHC isoform switching.
- WFA treatment lowered elevated circulating Ang II levels and ameliorated pro-inflammatory markers via the AT1R pathway.
Conclusions:
- Ovarian cancer induces cardiac cachexia and dysfunction in mice.
- WFA treatment demonstrates therapeutic potential by ameliorating cardiac cachexia and associated inflammation.
- WFA may be a promising agent for managing cardiac complications in cancer patients.
