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15d-PGJ2 Induces Apoptosis of MCF-7 and MDA-MB-231 Cells via Increased Intracellular Calcium and Activation of Caspases, Independent of ER_ and ER_ |
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| รหัสดีโอไอ | |
| Creator | Siti Nur Hasyila Muhammad |
| Title | 15d-PGJ2 Induces Apoptosis of MCF-7 and MDA-MB-231 Cells via Increased Intracellular Calcium and Activation of Caspases, Independent of ER_ and ER_ |
| Publisher | APJCP |
| Publication Year | 2559 |
| Journal Title | Asian Pacific Journal of Cancer Prevention |
| Journal Vol. | 17 |
| Journal No. | 7 |
| Page no. | 3223-3228 |
| Keyword | 15d-PGJ2, MCF-7, MDA-MB-231, apoptosis, estrogen receptor, intracellular calcium, caspase |
| Abstract | Reports indicate that 15-deoxy-delta-12,14-prostaglandin-J2 (15d-PGJ2) has anticancer activities, but its mechanisms of action have yet to be fully elucidated. We therefore investigated the effects of 15d-PGJ2 on the human breast cancer cell lines, MCF-7 (estrogen receptor ER_+/ER_+) and MDA-MB-231 (ER_-/ER_+). Cellular proliferation and cytotoxicity were determined using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays while apoptosis was determined by fluorescence microscopy and flow cytometry using annexin V-propidium iodide (PI) staining. ER expression was determined by Western blotting. Intracellular calcium was stained with Fluo-4 AM while intracellular caspase activities were detected with Caspase-FLICAย and measured by flow cytometry. We showed that 15d-PGJ2 caused a significant increase in apoptosis in MCF-7 and MDA-MB-231 cells. ER_ protein expression was reduced in treated MCF-7 cells but pre-incubation with the ER_ inhibitor๊ ICI 182 780๊ did not affect the percentage of apoptotic cells. The expression of ER_ was unchanged in both cell lines. In addition, 15d-PGJ2 increased intracellular calcium (Ca2+) staining and caspase 8, 9 and 3/7 activities. We therefore conclude that 15d-PGJ2 induces caspase-dependent apoptosis that is associated with an influx of intracellular Ca2+ with no involvement of ER signaling. |
