Ceramide accumulation is independent of camptothecin-induced apoptosis in prostate cancer LNCaP cells

Akao, Yukihiro; Kusakabe, Suzuno; Banno, Yoshiko; Kito, Mariko; Nakagawa, Yoshihito; Tamiya‐Koizumi, Keiko; Hattori, Masanori; Sawada, Michio; Hirabayasi, Yoshio; Ohishi, Nobuko; Nozawa, Yoshinori

doi:10.1016/s0006-291x(02)00462-x

Cited by 16 publications

(11 citation statements)

References 22 publications

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“…In line with previous studies (27)(28)(29)(30)35), a 72-hour camptothecin treatment induced 60% loss of cell viability in…”

Section: Resultssupporting

confidence: 92%

“…1A). In contrast to Wang et al (28), but in agreement with others (27,29,30,35,38), we did not find PC-3 cells totally resistant to camptothecin treatment. Flow cytometry analysis revealed that the decrease of cell viability observed in both cell lines could be attributed to apoptosis (Fig.…”

Section: Cancer Researchsupporting

confidence: 89%

“…Interestingly, S1P could block Taxol-induced apoptosis in ovarian cancer cells (26). We, therefore, investigated the ability of SphK1 to regulate apoptosis in LNCaP and PC-3 prostate cancer models in response to docetaxel (Taxotere), in comparison with camptothecin, a well-known inducer of apoptosis in LNCaP cells with little clinical relevance (27)(28)(29)(30); however, similarly to taxanes, camptothecin induces ceramide generation during apoptosis in several cancer models (30)(31)(32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, LNCaP cells seem to be quite sensitive to 0.1 to 1 Amol/L doses of camptothecin (27)(28)(29)(30)35), whereas the reported sensitivity of PC-3 cells to camptothecin ranges from moderately sensitive (35)(36)(37)(38) to completely resistant (28). Interestingly, the latter authors linked PC-3 resistance to the absence of ceramide generation and resensitized these cells to apoptosis by extracellular ceramide addition (28).…”

Section: Introductionmentioning

confidence: 99%

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Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models

et al. 2005

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Systemic chemotherapy was considered of modest efficacy in prostate cancer until the recent introduction of taxanes. We took advantage of the known differential effect of camptothecin and docetaxel on human PC-3 and LNCaP prostate cancer cells to determine their effect on sphingosine kinase-1 (SphK1) activity and subsequent ceramide/sphingosine 1-phosphate (S1P) balance in relation with cell survival. In vitro, docetaxel and camptothecin induced strong inhibition of SphK1 and elevation of the ceramide/S1P ratio only in cell lines sensitive to these drugs. SphK1 overexpression in both cell lines impaired the efficacy of chemotherapy by decreasing the ceramide/S1P ratio. Alternatively, silencing SphK1 by RNA interference or pharmacologic inhibition induced apoptosis coupled with ceramide elevation and loss of S1P. The differential effect of both chemotherapeutics was confirmed in an orthotopic PC-3/ green fluorescent protein model established in nude mice. Docetaxel induced a stronger SphK1 inhibition and ceramide/ S1P ratio elevation than camptothecin. This was accompanied by a smaller tumor volume and the reduced occurrence and number of metastases. SphK1-overexpressing PC-3 cells implanted in animals developed remarkably larger tumors and resistance to docetaxel treatment. These results provide the first in vivo demonstration of SphK1 as a sensor of chemotherapy. (Cancer Res 2005; 65(24): 11667-75)

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“…In line with previous studies (27)(28)(29)(30)35), a 72-hour camptothecin treatment induced 60% loss of cell viability in…”

Section: Resultssupporting

confidence: 92%

Section: Cancer Researchsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models

et al. 2005

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“…Cellular DNA extraction was done (as described in ref. 14). After electrophoresis of the total DNA from each sample on a 2.0% agarose gel, DNA was visualized by ethidium bromide staining.…”

Section: Methodsmentioning

confidence: 99%

Possible roles of vinexinβ in growth and paclitaxel sensitivity in human prostate cancer PC-3 cells

Mizutani

Nagata²,

Ito³

et al. 2007

Cancer Biology & Therapy

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High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation

Akao¹,

Banno

Nakagawa³

et al. 2006

Biochemical and Biophysical Research Communications

116

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Ceramide accumulation is independent of camptothecin-induced apoptosis in prostate cancer LNCaP cells

Cited by 16 publications

References 22 publications

Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models

Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models

Possible roles of vinexinβ in growth and paclitaxel sensitivity in human prostate cancer PC-3 cells

High expression of sphingosine kinase 1 and S1P receptors in chemotherapy-resistant prostate cancer PC3 cells and their camptothecin-induced up-regulation

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