PMID- 24739733 OWN - NLM STAT- MEDLINE DCOM- 20150528 LR - 20211021 IS - 1757-6512 (Electronic) IS - 1757-6512 (Linking) VI - 5 IP - 2 DP - 2014 Apr 16 TI - Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/AKT signaling. PG - 54 LID - 10.1186/scrt443 [doi] AB - INTRODUCTION: Although mesenchymal stem cells (MSCs) have antitumor potential in hepatocellular carcinoma and breast cancer cells, the antitumor mechanism of human umbilical cord mesenchymal stem cells (hUCMSCs) in prostate cancer cells still remains unclear. Thus, in the present study, we elucidated the antitumor activity of hUCMSCs in PC-3 prostate cancer cells in vitro and in vivo. METHODS: hUCMSCs were isolated from Wharton jelly of umbilical cord and characterized via induction of differentiations, osteogenesis, and adipogenesis. Antitumor effects of UCMSCs on tumor growth were evaluated in a co-culture condition with PC-3 prostate cancer cells. PC-3 cells were subcutaneously (sc) injected into the left flank of nude mice, and UCMSCs were sc injected into the right flank of the same mouse. RESULTS: We found that hUCMSCs inhibited the proliferation of PC-3 cells in the co-culture condition. Furthermore, co-culture of hUCMSCs induced the cleavage of caspase 9/3 and PARP, activated c-jun NH2-terminal kinase (JNK), and Bax, and attenuated the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/ AKT, extracellular signal-regulated kinase (ERK), and the expression of survival genes such as Bcl-2, Bcl-xL, Survivin, Mcl-1, and cIAP-1 in PC-3 cells in Western blotting assay. Conversely, we found that treatment of specific JNK inhibitor SP600125 suppressed the cleavages of caspase 9/3 and PARP induced by hUCMSCs in PC-3 cells by Western blotting and immunofluorescence assay. The homing of hUCMSCs to, and TUNEL-positive cells on, the K562 xenograft tumor region were detected in Nu/nu-BALB/c mouse. CONCLUSIONS: These results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment. FAU - Han, Ihn AU - Han I FAU - Yun, Miyong AU - Yun M FAU - Kim, Eun-Ok AU - Kim EO FAU - Kim, Bonglee AU - Kim B FAU - Jung, Min-Hyung AU - Jung MH FAU - Kim, Sung-Hoon AU - Kim SH LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20140416 PL - England TA - Stem Cell Res Ther JT - Stem cell research & therapy JID - 101527581 RN - EC 2.7.1.- (Phosphatidylinositol 3-Kinases) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - EC 2.7.12.2 (MAP Kinase Kinase 4) SB - IM RIN - Stem Cell Res Ther. 2018 Dec 27;9(1):354. PMID: 30587247 MH - Animals MH - Apoptosis/physiology MH - Cell Proliferation/physiology MH - Down-Regulation MH - Humans MH - MAP Kinase Kinase 4/*metabolism MH - Male MH - Mesenchymal Stem Cell Transplantation/*methods MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Mice MH - Mice, Inbred BALB C MH - Mice, Nude MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Prostatic Neoplasms/enzymology/pathology/*therapy MH - Proto-Oncogene Proteins c-akt/*metabolism MH - Signal Transduction MH - Umbilical Cord/cytology/*metabolism PMC - PMC4055109 EDAT- 2014/04/18 06:00 MHDA- 2015/05/29 06:00 PMCR- 2014/04/16 CRDT- 2014/04/18 06:00 PHST- 2013/09/11 00:00 [received] PHST- 2014/03/21 00:00 [accepted] PHST- 2014/04/18 06:00 [entrez] PHST- 2014/04/18 06:00 [pubmed] PHST- 2015/05/29 06:00 [medline] PHST- 2014/04/16 00:00 [pmc-release] AID - scrt443 [pii] AID - 10.1186/scrt443 [doi] PST - epublish SO - Stem Cell Res Ther. 2014 Apr 16;5(2):54. doi: 10.1186/scrt443.