FTY720 induces necrotic cell death and autophagy in ovarian cancer cells: A protective role of autophagy

Zhang, Ning; Qi, Yanfei; Wadham, Carol; Wang, Lijun; Warren, Alessandra; Di, Wen; Xia, Pu

doi:10.4161/auto.6.8.13614

Cited by 112 publications

(132 citation statements)

References 24 publications

Supporting

Mentioning

121

Contrasting

Order By: Relevance

“…Recently, FTY720 was shown to induce autophagy and necrosis in ovarian cancer cells. 42 As in our study, autophagy was shown to be protective against the cytotoxic effects of FTY720. Although the cytotoxic effect of FTY720 was independent of S1P signaling in both ALL and ovarian cancer cells, we have shown that S1P signaling induces autophagy which in turn exerts cell protection.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tsupporting

confidence: 72%

FTY720 produces caspase-independent cell death of acute lymphoblastic leukemia cells

Wallington-Beddoe¹,

Hewson²,

Bradstock³

et al. 2011

Autophagy

View full text Add to dashboard Cite

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tsupporting

confidence: 72%

FTY720 produces caspase-independent cell death of acute lymphoblastic leukemia cells

Wallington-Beddoe¹,

Hewson²,

Bradstock³

et al. 2011

Autophagy

View full text Add to dashboard Cite

“…Recently, different studies have suggested a dual role for autophagy in regulating cell death and it has recently emerged as a survival response of cancer cells to chemotherapy agents. 30 In this light, it has been reported that the autophagy induced by FTY720 worked as a protective function in ovarian cancer 31 and acute lymphoblastic leukemia cells; 32 on the other hand, a recent study on multiple myeloma cells has demonstrated the ability of FTY720 to induce autophagic cell death and apoptosis. 33,34 This discrepancy may be attributable to the complex and diverse interplays between autophagy and other mechanisms of cell death.…”

Section: Discussionmentioning

confidence: 99%

Sphingosine analog fingolimod (FTY720) increases radiation sensitivity of human breast cancer cells in vitro

Marvaso

Barone

Amodio

et al. 2014

Cancer Biology & Therapy

View full text Add to dashboard Cite

Radiotherapy is one of the most effective therapeutic strategies for breast cancer patients, although its efficacy may be reduced by intrinsic radiation resistance of cancer cells. Recent investigations demonstrate a link between cancer cell radio-resistance and activation of sphingosine kinase (SphK1), which plays a key role in the balance of lipid signaling molecules. Sphingosine kinase (SphK1) activity can alter the sphingosine-1-phosphate (S1P)/ceramide ratio leading to an imbalance in the sphingolipid rheostat. Fingolimod (FTY720) is a novel sphingosine analog and a potent immunosuppressive drug that acts as a SphK1 antagonist, inhibits the growth, and induces apoptosis in different human cancer cell lines. We sought to investigate the in vitro radiosensitizing effects of FTY720 on the MDA-MB-361 breast cancer cell line and to assess the effects elicited by radiation and FTY720 combined treatments. We found that FTY720 significantly increased anti-proliferative and pro-apoptotic effects induced by a single dose of ionizing radiation while causing autophagosome accumulation. At the molecular level, FTY720 significantly potentiated radiation effects on perturbation of signaling pathways involved in regulation of cell cycle and apoptosis, such as PI3K/AKT and MAPK. In conclusion, our data highlight a potent radiosensitizing effect of FTY720 on breast cancer cells and provide the basis of novel therapeutic strategies for breast cancer treatment

show abstract

“…In another case, FTY720 induced toxicity in the Raji cell line and primary CLL B cells, which was independent of activation of caspases or PARP processing (24). The mechanisms underlying the caspase-independent cell death are extremely complex, and include the downmodulation of cyclin D1 and phospho-Akt (23), activation of protein phosphatase 2A (PP2A), dephosphorylation of extracellular signal regulated kinase (ERK) 1/2 (24), the generation of reactive oxygen species (ROS) (23,25), and the induction of autophagy (13,(25)(26)(27)(28). However, the precise mechanisms remain unclear and are discussed later.…”

Section: Colorectal Cancermentioning

confidence: 99%

“…The immunosuppressive activity of FTY720 has been suggested to be related to its phosphorylation by sphingosine kinase 2 (SphK2) and subsequent modulation of G protein-coupled sphingosine-1-phosphate receptors (S1PRs) (S1PR1, S1PR3, S1PR4, S1PR5) that induce lymphopenia by altering lymphocyte trafficking (8). In addition to the potent immunosuppressive effects, evidence suggests that FTY720 has antitumor efficacy in multiple types of cancer, including breast (9), glioblastoma (10), prostate (11), lung (12), ovarian (13) and hematopoietic malignancies (14). This antitumor activity of FTY720 is reportedly independent of the phosphorylation of FTY720, which is different from the immunosuppressive effects of FTY720 (15).…”

Section: Introductionmentioning

confidence: 99%

FTY720 for cancer therapy (Review)

Zhang

Wang

et al. 2013

Oncology Reports

View full text Add to dashboard Cite

Abstract. 2-Amino-2-[2-(4-octylphenyl)]-1,3-propanediol hydrochloride (FTY720) is a potent immunosuppressant which has been approved by the Food and Drug Administration (FDA) as a new treatment for multiple sclerosis. As an immunosuppressant, it displays its anti-multiple sclerosis, immunosuppressive effects by activating sphingosine-1-phosphate receptors (S1PRs). In addition to the immunosuppressive effects, FTY720 also shows preclinical antitumor efficacy in several cancer models. In most cases, phosphorylation of FTY720 is not required for its cytotoxic effect, indicating the involvement of S1PR-independent mechanisms which are starkly different from the immunosuppressive property of FTY720. In the present study, we reviewed the rapidly advancing field of FTY720 in cancer therapy as well as some molecular targets of the unphosphorylated form of FTY720.

show abstract

FTY720 induces necrotic cell death and autophagy in ovarian cancer cells: A protective role of autophagy

Cited by 112 publications

References 24 publications

FTY720 produces caspase-independent cell death of acute lymphoblastic leukemia cells

FTY720 produces caspase-independent cell death of acute lymphoblastic leukemia cells

Sphingosine analog fingolimod (FTY720) increases radiation sensitivity of human breast cancer cells in vitro

FTY720 for cancer therapy (Review)

Contact Info

Product

Resources

About