Inhibition of p53 sensitizes MCF-7 cells to ceramide treatment

Abstract

Abstract. Ceramide signaling plays an important role in tumor progression and development of chemoresistance, and ceramide-based therapies are proposed as potential therapeutic tools for the treatment of breast cancer. We investigated the effect of exogenous ceramide on the cell cycle progression of MCF-7 breast cancer cells. Ceramide induced a selective arrest of MCF-7 cells in the G 1 -phase, which was associated with a decreased expression of cyclins D and E and increased expression of p53 and p21. Interestingly, inhibition of p53 using pifithrin · or RNAi sensitized MCF-7 cells to ceramide-induced cell death. DNA content analysis suggested that sensitization of cells was due to an increased induction of apoptosis in MCF-7 cells. The increased sensitivity to ceramide, in the context of p53 inhibition, may be due to decreased expression of p21, as siRNA targeted to p21 also sensitized MCF-7 cells to ceramide-induced death. These data demonstrate that in tumors with inactivating mutations of p53, ceramide-based therapies might provide a novel and effective treatment option.

Retracted: Effects of RNA interference‐mediated silencing of toll‐like receptor 4 gene on proliferation and apoptosis of human breast cancer MCF‐7 and MDA‐MB‐231 cells: An in vitro study

“…The continued existence of CDK4 has been associated with maintenance of tumor cell proliferation (Yu et al, ). P53 is a transcription factor that senses DNA damage, DNA repair, cell apoptosis, and cell cycle arrest; moreover, inactivating mutations of p53 can conduce uncontrollable growth of tumor cells and is of frequent occurrence in cancers (Struckhoff, Patel, & Beckman, ). Bcl‐2, a gene from the Bcl family of genes that encodes specific protein, which regulates programmed cell death in pathological, and pathological conditions, is a representative anti‐apoptotic protein; the levels of Bcl‐2 affects cellular fates, death, or survival (Lim et al, ).…”

Comparative lipidomics of 5-Fluorouracil–sensitive and –resistant colorectal cancer cells reveals altered sphingomyelin and ceramide controlled by acid sphingomyelinase (SMPD1)

“…In addition, we confirmed the overall decrease of Cer in DLD-1/5-FU cells compared to sensitive DLD-1 cells. It can be noted that Cer species are intracellular messengers that facilitate several signaling pathways that lead to cell cycle arrest 47 , apoptosis [48][49][50] , and autophagic responses 51,52 . In particular, C18-Cer induces cancer cell death and is an essential lipid for tumor suppression [53][54][55] .…”