Parabens, widely used preservatives in cosmetics, pharmaceuticals, and food products, have raised significant health concerns due to their endocrine-disrupting potential and possible carcinogenic effects. A study published in Discover Oncology explores the molecular mechanisms underlying paraben-induced breast cancer by integrating network toxicology, immune infiltration analysis, and molecular docking techniques to identify key gene targets and their roles in breast carcinogenesis.
Three core genes (ESR1, ESR2, and SERPINE1) were identified as central players in the protein-protein interaction network related to paraben exposure and breast cancer. ESR1 (Estrogen Receptor alpha) is pivotal in estrogen receptor-positive (ER+) breast cancer, which accounts for approximately 70% of breast cancer cases. ESR2 (Estrogen Receptor beta) plays a regulatory role in breast tissue homeostasis and is generally expressed at lower levels in breast cancer. SERPINE1 (plasminogen activator inhibitor-1) is involved in extracellular matrix remodeling and is associated with poor cancer prognosis and enhanced DNA repair mechanisms that promote tumor survival.
ESR1 mediates the effects of estrogen in promoting mammary cell proliferation and tumor growth. Paraben binding to ESR1 may lead to aberrant receptor activation, mimicking estrogen’s effects and potentially accelerating tumor initiation and progression. ESR1 mutations, often emerging during endocrine therapy, contribute to therapy resistance, highlighting the clinical importance of targeting this receptor.
ESR2 is considered protective in normal breast physiology by regulating cell differentiation and apoptosis. Paraben interference with ESR2 could disrupt these protective mechanisms, allowing for uncontrolled cell growth and transformation into malignant cells. Genetic polymorphisms in ESR2 may further modulate individual susceptibility to breast cancer and responses to endocrine therapies.
SERPINE1 plays a role in tumor progression by facilitating extracellular matrix remodeling and enhancing DNA repair processes, which may contribute to resistance to treatments like radiotherapy. Although direct binding between paraben and SERPINE1 remains to be conclusively demonstrated, paraben’s endocrine disruption could modulate SERPINE1-related signaling pathways, thus promoting carcinogenesis.
Parabens have been detected in various human tissues, including breast tissue, raising concerns about their bioaccumulation and chronic toxicity. Beyond breast cancer, parabens have been linked to endocrine disruption, infertility, neurotoxicity, and metabolic disorders. Their weak estrogenic activity enables them to interfere with the hormonal balance by binding to estrogen receptors and disrupting thyroid function, among other endocrine axes. By disrupting hormonal signaling and modulating immune infiltration, parabens may contribute to breast tumor initiation, progression, and immune evasion. These findings emphasize the need for cautious use of parabens in consumer products and the development of targeted therapies addressing the molecular mechanisms involved in paraben-induced breast carcinogenesis.
Sources: Discover Oncology