RETRACTED ARTICLE: Umbilical cord tissue-derived mesenchymal stem cells induce apoptosis in PC-3 prostate cancer cells through activation of JNK and downregulation of PI3K/AKT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

Abstract

IntroductionAlthough 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.MethodshUCMSCs 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.ResultsWe 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.ConclusionsThese results suggest that UCMSCs inhibit tumor growth and have the antitumor potential for PC-3 prostate cancer treatment.

Wharton's jelly mesenchymal stromal cells have contrasting effects on proliferation and phenotype of cancer stem cells from different subtypes of lung cancer

“…Previous studies that investigated a possible role of WJMSC in oncology have shown that these cells not only reduce the growth rate in human breast carcinoma [8] and prostate cancer [9], but also inhibit the proliferation of human osteosarcoma, ovarian carcinoma, Burkitt's lymphoma [10] and glioblastoma multiforme [31] cell lines in vitro. These findings are in keeping with the inhibiting effect exerted specifically by WJMSC on SCC-LCSC.…”

“…from amniotic fluid, umbilical cord blood and umbilical cord) harbor therapeutic potential in cancer treatment, as they can target the tumor site and reduce tumor burden [7]. In particular, WJMSC have been reported to reduce the growth of human breast carcinoma [8], prostate cancer [9], osteosarcoma and ovarian carcinoma cells [10].…”

Discarded Wharton jelly of the human umbilical cord: a viable source for mesenchymal stromal cells

“…WJ-MSCs possess cytokines and growth factor receptors, which allow them to be vital tools for cancer therapy. In such therapy, WJ-MCSs drastically weaken the cancerous tumors by secreting therapeutic proteins which promote the cancerous cells to undergo cell death and to stop the cell cycle [46]; moreover, WJ-MSCs enhance the immune response to cancer cells. With the minimum risk of spreading the cancer cells throughout the body or to the MSC donor, WJ-MSCs have the potential to serve as vehicles for delivery of tumor suppressive genes and anticancer drugs occur.…”

Human-derived normal mesenchymal stem/stromal cells in anticancer therapies

“…Another study showed that AT-MSCs increase cell viability of prostate tumor cell lines LNCaP and LNCaP-Bic, but no effect was observed for Du145 or PC3. UC-MSCs induce apoptosis in prostate cancer cell line PC-3 and attenuate bladder tumor cell growth in vitro and in vivo 36. However, BM-MSCs do not inhibit the proliferation of renal cell carcinoma cell lines (RCC42 and RCC52), but increase their migratory ability and invasiveness in vitro 37.…”