Increased ceramide production sensitizes breast cancer cell response to chemotherapy

Abstract

This study clearly demonstrated that the decreased ceramide production via up-regulating UGCG was involved in the resistance of breast cancer cells to chemotherapy. Stimulating ceramide or decreasing UGCG can potentially be useful for breast cancer treatment.

Ceramide Metabolism Balance, a Multifaceted Factor in Critical Steps of Breast Cancer Development

“…Indeed, the use of ceramides as coadjuvant therapy with different antineoplastics, is a novel treatment option due to its multifactorial participation in the structure and function of MAMs [ 84 ]. In line with this notion, ceramides are bioactive lipids that modulate processes such as proliferation and cell cycle, key events in the development of cancer [ 19 , 20 ]. Various reports have shown that cancer cells strictly modulate ceramide metabolism [ 19 , 20 , 85 ].…”

“…In line with this notion, ceramides are bioactive lipids that modulate processes such as proliferation and cell cycle, key events in the development of cancer [ 19 , 20 ]. Various reports have shown that cancer cells strictly modulate ceramide metabolism [ 19 , 20 , 85 ]. For instance, sphingolipid metabolism has been reported to regulate cancer development, progression, metastasis and resistance to therapy, some mechanisms have been described to explain how ceramides could regulate these processes specifically in breast cancer [ 19 , 20 ].…”

“…Several cell pathways have been proposed as triggers of neoplastic processes in TNBC, such as CD73, CD133, IMP3, ABCG2, HSF1 and PI3K/AKT/mTOR [ 150 , 151 , 152 , 153 , 154 , 155 ]. In breast cancer patients studied by Che J., et al, it has been found that after exposition to doxorubicin, cyclophosphamide, fluorouracil or its combination, ceramides levels decreased, indicating that its down-regulation is a common intrinsic response against breast cancer chemotherapy [ 20 ]. This subside response of ceramides concentration was determined in mammary tumor tissue, while in untreated women the levels remain unchanged [ 5 ].…”

“…Paradoxically, ceramides function in apoptosis development has allowed a more complex visualization of them, such as their role in cell differentiation and proliferation signaling pathways [ 17 , 18 ]. Ceramides have been described as regulatory lipids that modulate various sides of cell growth, survival, senescence, and apoptosis in cancer [ 19 , 20 ]. Wherein, a correlation between the levels of ceramides and the tumor stage has been demonstrated, ceramides metabolism has also been associated to chemotherapy resistance [ 19 , 20 ].…”

“…Ceramides have been described as regulatory lipids that modulate various sides of cell growth, survival, senescence, and apoptosis in cancer [ 19 , 20 ]. Wherein, a correlation between the levels of ceramides and the tumor stage has been demonstrated, ceramides metabolism has also been associated to chemotherapy resistance [ 19 , 20 ]. Then, ceramides play important roles in the regulation of cancer progression, and are linked to their function in meta-inflammation, a condition that associates overnutrition and obesity with a chronic low-grade inflammatory state [ 21 , 22 ], representing a key factor in the regulation of pathological processes.…”