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The Anticancer Effects and Therapeutic Potential of Kaempferol in Triple-Negative Breast Cancer
Sukhmandeep Kaur1, Patricia Mendonca2, Karam F A Soliman1
1Division of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Institute of Public Health, Florida A&M University, Tallahassee, FL 32307, USA.
Abstract:
Breast cancer is the second-leading cause of cancer death among women in the United States. Triple-negative breast cancer (TNBC), a subtype of breast cancer, is an aggressive phenotype that lacks estrogen (ER), progesterone (PR), and human epidermal growth (HER-2) receptors, which is challenging to treat with standardized hormonal therapy. Kaempferol is a natural flavonoid with antioxidant, anti-inflammatory, neuroprotective, and anticancer effects. Besides anti-tumorigenic, antiproliferative, and apoptotic effects, kaempferol protects non-cancerous cells. Kaempferol showed anti-breast cancer effects by inducing DNA damage and increasing caspase 3, caspase 9, and pAMT expression, modifying ROS production by Nrf2 modulation, inducing apoptosis by increasing cleaved PARP and Bax and downregulating Bcl-2 expression, inducing cell cycle arrest at the G2/M phase; inhibiting immune evasion by modulating the JAK-STAT3 pathway; and inhibiting the angiogenic and metastatic potential of tumors by downregulating MMP-3 and MMP-9 levels. Kaempferol holds promise for boosting the efficacy of anticancer agents, complementing their effects, or reversing developed chemoresistance. Exploring novel TNBC molecular targets with kaempferol could elucidate its mechanisms and identify strategies to overcome limitations for clinical application. This review summarizes the latest research on kaempferol's potential as an anti-TNBC agent, highlighting promising but underexplored molecular pathways and delivery challenges that warrant further investigation to achieve successful clinical translation.
Insights
Kaempferol, a natural flavonoid, demonstrates significant potential against triple-negative breast cancer (TNBC) by inducing cell death and inhibiting tumor growth. Further research into its molecular targets and delivery methods is crucial for clinical application.
Area of Science:
- Oncology
- Natural Products Chemistry
- Molecular Biology
Background:
- Triple-negative breast cancer (TNBC) is an aggressive subtype lacking ER, PR, and HER-2 receptors, posing treatment challenges.
- Kaempferol, a natural flavonoid, exhibits antioxidant, anti-inflammatory, and anticancer properties.
- Current treatments for TNBC are limited, necessitating exploration of novel therapeutic agents.
Purpose of the Study:
- To review the current research on kaempferol's potential as an anti-TNBC agent.
- To highlight underexplored molecular pathways targeted by kaempferol in TNBC.
- To identify challenges and opportunities for the clinical translation of kaempferol for TNBC treatment.
Main Methods:
- Literature review of preclinical studies on kaempferol and TNBC.
- Analysis of kaempferol's molecular mechanisms, including DNA damage, apoptosis induction, cell cycle arrest, and pathway modulation.
- Evaluation of kaempferol's effects on tumor angiogenesis and metastasis.
Main Results:
- Kaempferol demonstrates anti-TNBC effects by inducing DNA damage, apoptosis (increasing cleaved PARP, Bax; downregulating Bcl-2), and cell cycle arrest (G2/M phase).
- Kaempferol modulates ROS production via Nrf2, inhibits immune evasion through the JAK-STAT3 pathway, and reduces tumor angiogenesis and metastasis (downregulating MMP-3, MMP-9).
- Kaempferol shows promise in enhancing anticancer agent efficacy and overcoming chemoresistance.
Conclusions:
- Kaempferol exhibits multifaceted anti-TNBC properties, targeting key oncogenic pathways.
- Further investigation into novel molecular targets and overcoming delivery challenges is essential for clinical application.
- Kaempferol represents a promising natural compound for developing novel TNBC therapies.
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