The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers

Gotō, Tomoko; Takano, Masashi; Hirata, Junko; Tsuda, Hitoshi

doi:10.1038/sj.bjc.6604279

Cited by 60 publications

(50 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We have previously shown that phosphorylated FOXO1 is overexpressed in gastric cancer specimens and that FOXO1 inactivation is related to better prognosis of gastric cancer patients [18]. Although FOXO proteins, especially FOXO1 and FOXO3, have been reported to be related to chemoresistance in various cancer cells [8][9][10][19][20][21], their involvement in chemoresistance of gastric cancer cells has not been reported. In the present study, we used two gastric cancer cell lines, MKN45 and SNU-601, with constitutive FOXO1 expression and found that CDDP treatment increased the levels of FOXO1 protein expression and activation.…”

Section: Discussionmentioning

confidence: 99%

“…FOXO1 increased doxorubicin resistance in breast cancer cells [8] and paclitaxel resistance in ovarian cancer cells [9], whereas it decreased CDDP resistance in ovarian cancer cells [10]. Thus, the effect of FOXO1 on the chemoresistance of cancer cells may differ according to the drug and cell type investigated.…”

Section: Introductionmentioning

confidence: 99%

“…The function of FOXO1 in chemoresistance in cancer cells has been evaluated in in vitro studies [8][9][10]. FOXO1 increased doxorubicin resistance in breast cancer cells [8] and paclitaxel resistance in ovarian cancer cells [9], whereas it decreased CDDP resistance in ovarian cancer cells [10].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway

Park

Yoon

et al. 2013

Gastric Cancer

View full text Add to dashboard Cite

Background Cisplatin (CDDP) is one of the most important chemotherapeutic agents in the treatment of advanced gastric cancer, but its efficacy is limited by CDDP resistance. Because the transcription factor FOXO1 is related to chemoresistance in various cancer cells, we investigated the function of FOXO1 in CDDP resistance in human gastric cancer cells. Methods Human gastric cancer cell lines MKN45 and SNU-601 were used. FOXO1 activation was modulated by transfection of FOXO1 AAA mutant gene or FOXO1 shRNA. The effects of FOXO1 on cell growth and CDDP cytotoxicity were assessed by crystal violet assay. Protein expressions of FOXO1, p110a, pAkt, and Akt were analyzed by Western blotting, and FOXO1 mRNA expression was evaluated by semiquantitative reverse transcription-polymerase chain reaction. FOXO1 activity was determined by luciferase reporter assay, and cell apoptosis was assessed by DAPI staining and Western blotting for PARP cleavage. Results Cisplatin treatment induced FOXO1 expression and activation in both gastric cancer cell lines. FOXO1 overexpression increased the CDDP resistance without changes in cell growth, whereas FOXO1 silencing enhanced CDDP cytotoxicity along with apoptotic characteristics. Both constitutive and CDDP-induced FOXO1 activations were accompanied by an increase in p110a and pAkt expression. Furthermore, Akt inhibition by LY294002 treatment restored the CDDP cytotoxicity that was suppressed by FOXO1 overexpression. Conclusion FOXO1 inhibits CDDP-induced apoptosis in gastric cancer cells via activating PI3K/Akt pathway. Thus, FOXO1 may be an useful pharmacological indicator to predict CDDP efficacy in gastric cancer treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway

Park

Yoon

et al. 2013

Gastric Cancer

View full text Add to dashboard Cite

show abstract

“…When cell death occurs, it takes place mainly via the intrinsic pathway of apoptosis. Among the apoptotic events initiated by paclitaxel, there have been included several modifications of Bcl-2 family proteins such as Bcl-2 and Bcl-xL phosphorylation, Bax activation (2,5), or Bim induction by Forkhead box O (FoxO) transcription factors (6,7).…”

Section: Introductionmentioning

confidence: 99%

Prostate Cancer Cell Response to Paclitaxel Is Affected by Abnormally Expressed Securin PTTG1

Castilla

Medina

et al. 2014

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

PTTG1 protein, the human securin, has a central role in sister chromatid separation during mitosis, and its altered expression has been reported in many tumor types. Paclitaxel is a widely used chemotherapeutic drug, whose mechanism of action is related to its ability to arrest cells in mitosis and the subsequent induction of the intrinsic apoptotic pathway. By using two prostate cancer cell lines with different responses to paclitaxel treatment, we have identified two situations in which PTTG1 influences cell fate differentially. In slippageprone PC3 cells, both PTTG1 downregulation and overexpression induce an increase in mitotic cells that is associated with diminished apoptosis after paclitaxel treatment. In LNCaP cells, however, PTTG1 downregulation prevents mitotic entry and, subsequently, inhibits mitosis-associated, paclitaxel-induced apoptosis. In contrast, PTTG1 overexpression induces an increase in mitotic cells and apoptosis after paclitaxel treatment. We have also identified a role for Mcl-1 protein in preventing apoptosis during mitosis in PC3 cells, as simultaneous PTTG1 and Mcl-1 silencing enhances mitosis-associated apoptosis after paclitaxel treatment. The finding that a more efficient mitotic arrest alone in PC3 cells is not enough to increase apoptosis was also confirmed with the observation that a selected paclitaxel-resistant PC3 cell line showed an apoptosis-resistant phenotype associated with increased mitosis upon paclitaxel treatment. These findings could contribute to identify putative responsive and nonresponsive cells and help us to approach incomplete responses to paclitaxel in the clinical setting. Mol Cancer Ther; 13(10); 2372-83. Ó2014 AACR.

show abstract

“…Phosphorylation and inactivation of forkhead box protein O1 (FOXO1) is an important mechanism by which Akt activation promotes cell survival (Rena et al, 1999). FOXO1 acts as a tumor suppressor in a variety of cancers including ovarian cancer (Goto et al, 2008;Xie et al, 2012). Several studies have demonstrated that the anticancer effect of curcumin is associated with the modulation of FOXO1 expression (Li et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

Zhao¹,

Zhang²,

Zhang³

et al. 2014

Asian Pacific Journal of Cancer Prevention

View full text Add to dashboard Cite

Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin (10-60 μM) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

show abstract

The involvement of FOXO1 in cytotoxic stress and drug-resistance induced by paclitaxel in ovarian cancers

Cited by 60 publications

References 28 publications

The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway

The forkhead transcription factor FOXO1 mediates cisplatin resistance in gastric cancer cells by activating phosphoinositide 3-kinase/Akt pathway

Prostate Cancer Cell Response to Paclitaxel Is Affected by Abnormally Expressed Securin PTTG1

Induction of MicroRNA-9 Mediates Cytotoxicity of Curcumin Against SKOV3 Ovarian Cancer Cells

Contact Info

Product

Resources

About