Bioactive sphingolipids in docetaxel-induced apoptosis in human prostate cancer cells

Bassoy, Esen Yonca; Baran, Yusuf

doi:10.1016/j.biopha.2011.10.003

Cited by 12 publications

(14 citation statements)

References 27 publications

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“…According to our studies, SKi increases the cytotoxic effects of dasatinib on K-562 and Meg-01 human chronic myeloid leukemia cells [118]. It has also been reported that there are synergistic cytotoxic and apoptotic effects between PDMP and docetaxel on DU-145 and PC-3 human prostate cancer cells [119].…”

Section: Sphingosine Kinase Inhibitorssupporting

confidence: 59%

“…In one of our studies we found that the sensitivity of human chronic myeloid leukemia cells increased to nilotinib via coadministration of C8-ceramide [117]. Combination of C:8 ceramide increased the antiproliferative and apoptotic effects of resveratrol on chronic myeloid leukemia [114] and acute myeloid leukemia [115] cells while combination of docetaxel with C8:ceramide showed significant synergistic apoptosis on prostate cancer cell lines [119]. In a recent report, Zhu et al [191] investigated the synergistic effects of histone deacetylase inhibitor, TSA, and C6ceramide both in vitro and in vivo pancreatic and ovarian cancer models.…”

Section: C16-serinol Lc 124mentioning

confidence: 62%

“…We also showed that PDMP increases the cytotoxic effects of dasatinib on K-562 and Meg-01 human chronic myeloid leukemia cells [118]. Moreover, it has been revealed that there are synergistic cytotoxic and apoptotic effects between PDMP and docetaxel on DU-145 and PC-3 human prostate cancer cells [119]. In human U87-MG glioma cells with active p53, PDMP triggered the activation of caspases induced by radiation via accumulating intracellular ceramide [120].…”

Section: -Phenyl-2-palmitoylamino-3-morpholino-1-propanol (Ppmp)mentioning

confidence: 81%

“…In other words, manipulation of sphingolipid metabolism is considered to be a good approach for development of novel therapies. It is believed that a combination therapy with conventional cytotoxic drugs while increasing the levels of pro-apoptotic ceramide can be more beneficial [116][117][118][119]. However, because apoptotic sphingolipids may cause cytotoxicity in non-cancerous cells, delivering cytotoxic species specifically to the malignant cells remains as an important issue that should be concentrated on.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

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Novel Agents Targeting Bioactive Sphingolipids for the Treatment of Cancer

Adan-Gokbulut¹,

Yandım²,

Iskender³

et al. 2012

CMC

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Sphingolipids are a class of lipids that have important functions in a variety of cellular processes such as, differentiation, proliferation, senescence, apoptosis and chemotherapeutic resistance. The most widely studied bioactive shingolipids include ceramides, dihydroceramide (dhCer), ceramide-1-phosphate (C1P), glucosyl-ceramide (GluCer), sphingosine and sphingosine-1-phosphate (S1P). Although the length of fatty acid chain affects the physiological role, ceramides and sphingosine are known to induce apoptosis whereas C1P, S1P and GluCer induce proliferation of cells, which causes the development of chemoresistance. Previous studies have implicated the significance of bioactive shingolipids in oncogenesis, cancer progression and drug-and radiation-resistance. Therefore, targeting the elements of sphingolipid metabolism appears important for the development of novel therapeutics or to increase the effectiveness of the current treatment strategies. Some approaches involve the development of synthetic ceramide analogs, small molecule inhibitors of enzymes such as sphingosine kinase, acid ceramidase or ceramide synthase that catalyze ceramide catabolism or its conversion to various molecular species and S1P receptor antagonists. These approaches mainly aim to up-regulate the levels of apoptotic shingolipids while the proliferative ones are down-regulated, or to directly deliver cytotoxic sphingolipids like short-chain ceramide analogs to tumor cells. It is suggested that a combination therapy with conventional cytotoxic approaches while preventing the conversion of ceramide to S1P and consequently increasing the ceramide levels would be more beneficial. This review compiles the current knowledge about sphingolipids, and mainly focuses on novel agents modulating sphingolipid pathways that represent recent therapeutic strategies for the treatment of cancer.

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Section: Sphingosine Kinase Inhibitorssupporting

confidence: 59%

Section: C16-serinol Lc 124mentioning

confidence: 62%

Section: -Phenyl-2-palmitoylamino-3-morpholino-1-propanol (Ppmp)mentioning

confidence: 81%

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

See 2 more Smart Citations

Novel Agents Targeting Bioactive Sphingolipids for the Treatment of Cancer

Adan-Gokbulut¹,

Yandım²,

Iskender³

et al. 2012

CMC

View full text Add to dashboard Cite

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“…Our group has also shown that the inhibition of GCS with PDMP increased anti-proliferative and apoptotic effects of imatinib [86], nilotinib [87], and dasatinib [88] on chronic myeloid leukemia cells synergistically. GCS inhibition causes enhanced cytotoxic and apoptotic responses in human prostate cancer cells in response to docetaxel treatment [89]. It was also demonstrated that inhibition of GCS reversed resistance to doxorubicin and vincristine in leukemia [90,91].…”

Section: Glucosylceramide Synthase In Cancer Therapymentioning

confidence: 99%

Therapeutic potential of targeting ceramide/glucosylceramide pathway in cancer

Yandım

Apohan

Baran

2012

Cancer Chemother Pharmacol

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Sphingolipids including ceramides and its derivatives such as ceramide-1-phosphate, glucosylceramide (GlcCer), and sphingosine-1-phosphate are essential structural components of cell membranes. They now recognized as novel bioeffector molecules which control various aspects of cell growth, proliferation, apoptosis, and drug resistance. Ceramide, the central molecule of sphingolipid metabolism, generally mediates anti-proliferative responses such as inhibition of cell growth, induction of apoptosis, and/or modulation of senescence. There are two major classes of sphingolipids. One of them is glycosphingolipids which are synthesized from the hydrophobic molecule, ceramide. GlcCer, generated by glucosylceramide synthase (GCS) that transfers the glucose from UDPglucose to ceramide, is an important glycosphingolipid metabolic intermediate. GCS regulates the balance between apoptotic ceramide and antiapoptotic GlcCer. Downregulation or inhibition of GCS results in increased apoptosis and decreased drug resistance. The mechanism underlying the drug resistance which develops with increased glucosylceramide expression is associated with P-glycoprotein. In various types of cancers, overexpression of GCS has been observed which renders GCS a good target for the treatment of cancer. This review summarizes our current knowledge on the structure and functions of glucosylceramide synthase and glucosylceramide and on the roles of glucosylceramide synthase in cancer therapy and drug resistance.

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