Chemotherapy has been shown to cause muscle loss in cancer patients in the past, but a recent Penn State study discovered that it may also alter how the body grows new muscle at lower dosages than previously thought, which could have ramifications for therapies and rehab programs.
Chemotherapy medications, according to the researchers, can damage the mitochondria within cells, which can lead to muscle tissue loss through a process known as oxidative stress.
The researchers looked at three distinct chemotherapy medicines in cultured muscle cells at levels that were too low to cause oxidative stress in their latest study. They discovered that the reduced amounts of medicines still had an effect on muscle cells by interfering with the process of protein synthesis, which creates muscle.
While the findings need to be replicated in humans, Gustavo Nader, associate professor of kinesiology, believes they could have ramifications for cancer treatment in the future.
“Eventually, it may be that the implementation of cancer treatments should consider that even at low doses that do not cause oxidative stress, some chemotherapy drugs may still promote the loss of muscle tissue,” Nader said. “The tumor is already making you weak, it’s contributing to the loss of muscle mass, and the chemo drugs are helping the tumor to accomplish that.”
For a long time, people thought the problem with chemo and muscle loss was an issue with degrading the proteins that already existed in the muscle. So, a lot of research and treatments in the past had the goal of preventing protein degradation. But our study points to there also being a problem with protein synthesis, or the building of new muscle proteins, as well.Gustavo Nader
Furthermore, according to Nader, the findings published recently in the American Journal of Physiology Cell Physiology have the potential to transform how health care practitioners think about how chemotherapy impacts the body.
“For a long time, people thought the problem with chemo and muscle loss was an issue with degrading the proteins that already existed in the muscle,” Nader said. “So, a lot of research and treatments in the past had the goal of preventing protein degradation. But our study points to there also being a problem with protein synthesis, or the building of new muscle proteins, as well.”
The findings, according to Nader, could transform the way health care providers think about nonpharmaceutical cancer therapies and programs, in addition to having consequences for chemotherapy treatment.
According to Nader, persons with cancer are frequently advised to exercise in order to regain muscle mass lost as a result of their illness and treatment. However, if chemotherapy has an effect on the body’s ability to create new muscle, it will have to be factored into exercise plans.
“If you’re still receiving chemotherapy while going through an exercise rehabilitation program, it’s possible that chemo could impede your progress,” Nader said. “During exercise interventions, the muscles need to make ribosomes, which then build new proteins. But if the drug is blocking that, the rehab might not be successful. The implications of this work could be huge, and I think we’re beginning to see the tip of the iceberg.”
The researchers tested the effects of three regularly used chemotherapy medications on muscle cells generated in their lab, including paclitaxel, doxorubicin, and marizomib. They used just enough of each medicine to have an effect on the cells without causing oxidative stress, which is known to harm muscle cells.
The medications were administered to the cells for up to 48 hours, and the process of producing new ribosomes was disrupted in all three cases. These new findings reveal one method in which chemotherapy affects the production of muscle proteins since ribosomes are required for protein synthesis.
“We chose to do this study in cultured cells because in a living organism, chemotherapy also affects nonmuscle cells like those in the pancreas and liver, which can then trigger their own processes that can also affect muscle cells,” Nader said. “We wanted a very controlled environment with only the muscle cells and chemotherapy drugs so we can examine very precisely how they interact.”
Bin Guo, Penn State; Devasier Bennet, Penn State; Daniel J. Belcher, a graduate student at Penn State; and Hyo-Gun Kim, a doctoral student at Penn State, also participated in this work. The National Institutes of Health helped support this research.