Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma
An endogenous anticancer agent, 15-deoxy -Δ12,14-prostaglandin J2 (15d-PGJ2) induces apoptosis in the chemoresistant renal cell carcinoma (RCC). Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor for 15d-PGJ2, and mediates the cytotoxicity of 15d-PGJ2 in many cancerous cells....
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Elsevier
2017-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580816302886 |
| _version_ | 1818257393701617664 |
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| author | Yasuhiro Yamamoto Takehiro Yamamoto Hiromi Koma Ayaka Nishii Tatsurou Yagami |
| author_facet | Yasuhiro Yamamoto Takehiro Yamamoto Hiromi Koma Ayaka Nishii Tatsurou Yagami |
| author_sort | Yasuhiro Yamamoto |
| collection | DOAJ |
| description | An endogenous anticancer agent, 15-deoxy -Δ12,14-prostaglandin J2 (15d-PGJ2) induces apoptosis in the chemoresistant renal cell carcinoma (RCC). Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor for 15d-PGJ2, and mediates the cytotoxicity of 15d-PGJ2 in many cancerous cells. However, 15d-PGJ2 induces apoptosis independently of PPARγ in human RCC cell line such as Caki-2. In the present study, we found that 15d-PGJ2 ameliorated the chemoresistance to one of anthracycline antibiotics, doxorubicin, in Caki-2 cells. Doxorubicin alone exhibited weak cytotoxicity at the concentrations effective for other cancer cells such as Hela cells. In addition, it did not activate caspase 3. However, the cytotoxicity of doxorubicin was increased remarkably and accompanied with the caspase- 3 activation in the presence of 15d-PGJ2. Doxorubicin alone damaged plasma membrane, and the combined application of 15d-PGJ2 with doxorubicin increased the membrane permeability slightly. PPARγ was involved in neither the anti-tumor activity nor the synergistic effect of 15d-PGJ2. 15d-PGJ2 induces apoptosis in Caki-2 cells via suppressing the phosphoinositide 3-kinase (PI3K)-Akt pathway. The effect of PI3K inhibitor on the cytotoxicity of doxorubicin was additive, but not synergistic. Although the PI3K inhibitor mimicked the cytotoxicity of 15d-PGJ2, it might not be involved in the synergism between 15d-PGJ2 and doxorubicin. In conclusion, 15d-PGJ2 enhanced the chemosensitivity of doxorubicin via the pathway independent of PPARγ and PI3K. |
| first_indexed | 2024-12-12T17:42:56Z |
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| id | doaj.art-6b1541e1346b4ef9ae1aee375092f95e |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-12-12T17:42:56Z |
| publishDate | 2017-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-6b1541e1346b4ef9ae1aee375092f95e2022-12-22T00:17:01ZengElsevierBiochemistry and Biophysics Reports2405-58082017-03-019C616610.1016/j.bbrep.2016.11.004Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinomaYasuhiro Yamamoto0Takehiro Yamamoto1Hiromi Koma2Ayaka Nishii3Tatsurou Yagami4Division of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, JapanHyogo Prefectural Kobe High School, 1-5-1 Shironoshita-dori, Nada-ku, Kobe, Hyogo 657-0804, JapanDivision of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, JapanDivision of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, JapanDivision of Physiology, Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 2-1, kami-ohno 7-Chome, Himeji, Hyogo 670-8524, JapanAn endogenous anticancer agent, 15-deoxy -Δ12,14-prostaglandin J2 (15d-PGJ2) induces apoptosis in the chemoresistant renal cell carcinoma (RCC). Peroxisome proliferator-activated receptor-γ (PPARγ) is a nuclear receptor for 15d-PGJ2, and mediates the cytotoxicity of 15d-PGJ2 in many cancerous cells. However, 15d-PGJ2 induces apoptosis independently of PPARγ in human RCC cell line such as Caki-2. In the present study, we found that 15d-PGJ2 ameliorated the chemoresistance to one of anthracycline antibiotics, doxorubicin, in Caki-2 cells. Doxorubicin alone exhibited weak cytotoxicity at the concentrations effective for other cancer cells such as Hela cells. In addition, it did not activate caspase 3. However, the cytotoxicity of doxorubicin was increased remarkably and accompanied with the caspase- 3 activation in the presence of 15d-PGJ2. Doxorubicin alone damaged plasma membrane, and the combined application of 15d-PGJ2 with doxorubicin increased the membrane permeability slightly. PPARγ was involved in neither the anti-tumor activity nor the synergistic effect of 15d-PGJ2. 15d-PGJ2 induces apoptosis in Caki-2 cells via suppressing the phosphoinositide 3-kinase (PI3K)-Akt pathway. The effect of PI3K inhibitor on the cytotoxicity of doxorubicin was additive, but not synergistic. Although the PI3K inhibitor mimicked the cytotoxicity of 15d-PGJ2, it might not be involved in the synergism between 15d-PGJ2 and doxorubicin. In conclusion, 15d-PGJ2 enhanced the chemosensitivity of doxorubicin via the pathway independent of PPARγ and PI3K.http://www.sciencedirect.com/science/article/pii/S2405580816302886Renal cell carcinoma15-deoxy Δ12,14-prostaglandin J2DoxorubicinPhosphoinositide 3-kinaseChemoresistant |
| spellingShingle | Yasuhiro Yamamoto Takehiro Yamamoto Hiromi Koma Ayaka Nishii Tatsurou Yagami Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma Biochemistry and Biophysics Reports Renal cell carcinoma 15-deoxy Δ12,14-prostaglandin J2 Doxorubicin Phosphoinositide 3-kinase Chemoresistant |
| title | Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma |
| title_full | Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma |
| title_fullStr | Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma |
| title_full_unstemmed | Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma |
| title_short | Synergistic effects of 15-deoxy Δ12,14-prostaglandin J2 on the anti-tumor activity of doxorubicin in renal cell carcinoma |
| title_sort | synergistic effects of 15 deoxy δ12 14 prostaglandin j2 on the anti tumor activity of doxorubicin in renal cell carcinoma |
| topic | Renal cell carcinoma 15-deoxy Δ12,14-prostaglandin J2 Doxorubicin Phosphoinositide 3-kinase Chemoresistant |
| url | http://www.sciencedirect.com/science/article/pii/S2405580816302886 |
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