Curcumin induces apoptotic cell death in human pancreatic cancer cells via the miR-340/XIAP signaling pathway

Abstract

Abstract. The natural compound curcumin has previously been reported to inhibit pancreatic cancer cell growth. However, the underlying molecular mechanisms underlying this effect remain unclear. Results from the present study demonstrate that the miR-340/X-linked inhibitor of apoptosis (XIAP) signaling pathway mediates curcumin-induced pancreatic cancer cell apoptosis. miR-340 was identified to be significantly upregulated following curcumin treatment. In addition, treatment with curcumin or miR-340 induced pancreatic cancer cell apoptosis, whereas silencing endogenous miR-340 significantly inhibited the proapoptotic effect of curcumin. A luciferase reporter assay and western blot analysis identified that the oncogene XIAP is a direct target of miR-340. Furthermore, curcumin treatment significantly reduced XIAP expression, an effect that was rescued by treatment with anti-miR-340. The results of the present study suggest that the miR-340/XIAP signaling pathway is a downstream target of curcumin that mediates its proapoptotic effects on pancreatic cancer cells. This may provide the basis for novel treatment strategies for patients with pancreatic cancer.

RETRACTED ARTICLE: Curcumin inhibits proliferation, migration, invasion and promotes apoptosis of retinoblastoma cell lines through modulation of miR-99a and JAK/STAT pathway

“…Previous studies showed that the anti-tumor activities of curcumin are mainly due to the inhibition of proliferation, migration and invasion, as well as due to the induction of apoptosis [ 11 , 15 , 22 ]. This study revealed that curcumin significantly reduced the viability and colony formation of both SO-Rb50 and Y79 cells, and the IC50 value of curcumin in these two Rb cell lines is about 35 μM.…”

“…It has been reported that curcumin exerted anti-tumor activities via modulation of various miRNAs, including miR-21 [ 14 ], miR-340 [ 15 ] and miR-98 [ 16 ]. Curcumin could alter the expression of many miRNAs in Y79 cells [ 41 ], which may contribute to its anti-tumor properties in Rb.…”

Hepatitis B virus‐regulated growth of liver cancer cells occurs through the microRNA‐340‐5p‐activating transcription factor 7‐heat shock protein A member 1B axis

“…miRNAs are a class of short, endogenous, non‐coding RNAs that play important roles in gene regulation by binding to, and repressing the expression of target mRNAs in a sequence‐dependent method. In particular, a number of reports have identified miR‐340 as a tumor suppressor in HCC as well as several other cancers including ovarian cancer, breast cancer, colon cancer, glioblastoma, and pancreatic cancer . Consistent with these data, in a previous study, we found that miR‐340 expression was significantly downregulated in HCC tissues compared with normal liver tissues.…”

“…In particular, a number of reports have identified miR-340 as a tumor suppressor in HCC 9,10 as well as several other cancers including ovarian cancer, 11 breast cancer, 12 colon cancer, 13 glioblastoma, 14 and pancreatic cancer. 15 Consistent with these data, in a previous study, we found that miR-340 expression was significantly downregulated in HCC tissues compared with normal liver tissues. Furthermore, we showed that HBV could downregulate miR-340 in hepatoma cells, which facilitates their migration.…”

Investigational agents to enhance the efficacy of chemotherapy or radiation in pancreatic cancer

“…It consequently causes an induction of FOXO1 (forkhead box O1). A more recent study proposed that apoptosis induced by Cur is the result of activation of miR-340 and the downregulation of its target anti-protein, XIAP (X linked inhibitor of apoptosis protein) (Yang et al, 2017). The above studies demonstrate Cur's anticancer properties describe the mechanism and provide preliminary evidence for its potential use to sensitize PC cells to cytotoxic therapies.…”