Naringenin impairs mitochondrial function via ROS to induce apoptosis in tamoxifen resistant MCF-7 breast cancer
Lauren A Eanes1, Mayar Eldeeb1, Darrell Storholt1
1Department of Biology, University of North Carolina at Greensboro, Greensboro, North Carolina, United States of America.
Abstract:
Breast cancer is the second leading cause of cancer deaths among women. While tamoxifen, a commonly used drug therapy in breast cancer patients, is effective, many patients acquire tamoxifen resistance. Therefore, it is essential to identify alternative or combination therapeutics for the treatment of breast cancer. Naringenin, a naturally occurring flavonoid, has been reported to elicit antioxidant, anti-proliferative, and pro-apoptotic effects in cancer cells. The current study aimed to identify the mechanism by which naringenin induces apoptosis in tamoxifen-resistant breast cancer cells. The present study demonstrated that naringenin induced an increase in ROS, resulting in oxidative stress, impaired mitochondrial function, and apoptosis in tamoxifen-resistant breast cancer cells. Our study reports that naringenin specifically increases mitochondrial superoxide anions and hydrogen peroxide production while also causing mitochondrial dysfunction. These studies provide novel evidence for the mechanism by which naringenin induces apoptosis in tamoxifen-resistant breast cancer cells and supports the use of naringenin as a therapeutic on breast cancer cells and drug-resistant cancer cells.
Insights
Naringenin combats tamoxifen-resistant breast cancer by inducing oxidative stress and mitochondrial dysfunction, leading to cancer cell death. This natural flavonoid offers a promising therapeutic strategy for drug-resistant breast cancers.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Breast cancer remains a leading cause of mortality in women.
- Tamoxifen is a common therapy, but resistance develops in many patients.
- Alternative or combination treatments are crucial for managing tamoxifen-resistant breast cancer.
Purpose of the Study:
- To elucidate the mechanism by which naringenin induces apoptosis in tamoxifen-resistant breast cancer cells.
- To investigate naringenin's effects on reactive oxygen species (ROS) and mitochondrial function.
- To establish naringenin as a potential therapeutic agent for drug-resistant breast cancer.
Main Methods:
- Treatment of tamoxifen-resistant breast cancer cells with naringenin.
- Measurement of reactive oxygen species (ROS) production, including superoxide anions and hydrogen peroxide.
- Assessment of mitochondrial function and induction of apoptosis.
Main Results:
- Naringenin significantly increased ROS production, leading to oxidative stress in resistant cells.
- Impaired mitochondrial function was observed following naringenin treatment.
- Naringenin effectively induced apoptosis in tamoxifen-resistant breast cancer cells.
Conclusions:
- Naringenin induces apoptosis in tamoxifen-resistant breast cancer cells via increased ROS and mitochondrial dysfunction.
- Naringenin demonstrates potential as a therapeutic agent for breast cancer, including drug-resistant types.
- Further research supports naringenin's role in combination or alternative breast cancer therapies.
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