Curcumin Modulates Pancreatic Adenocarcinoma Cell-Derived Exosomal Function
#MMPMID26177391
Osterman CJ
; Lynch JC
; Leaf P
; Gonda A
; Ferguson Bennit HR
; Griffiths D
; Wall NR
PLoS One
2015[]; 10
(7
): e0132845
PMID26177391
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Pancreatic cancer has the highest mortality rates of all cancer types. One
potential explanation for the aggressiveness of this disease is that cancer cells
have been found to communicate with one another using membrane-bound vesicles
known as exosomes. These exosomes carry pro-survival molecules and increase the
proliferation, survival, and metastatic potential of recipient cells, suggesting
that tumor-derived exosomes are powerful drivers of tumor progression. Thus, to
successfully address and eradicate pancreatic cancer, it is imperative to develop
therapeutic strategies that neutralize cancer cells and exosomes simultaneously.
Curcumin, a turmeric root derivative, has been shown to have potent anti-cancer
and anti-inflammatory effects in vitro and in vivo. Recent studies have suggested
that exosomal curcumin exerts anti-inflammatory properties on recipient cells.
However, curcumin's effects on exosomal pro-tumor function have yet to be
determined. We hypothesize that curcumin will alter the pro-survival role of
exosomes from pancreatic cancer cells toward a pro-death role, resulting in
reduced cell viability of recipient pancreatic cancer cells. The main objective
of this study was to determine the functional alterations of exosomes released by
pancreatic cancer cells exposed to curcumin compared to exosomes from untreated
pancreatic cancer cells. We demonstrate, using an in vitro cell culture model
involving pancreatic adenocarcinoma cell lines PANC-1 and MIA PaCa-2, that
curcumin is incorporated into exosomes isolated from curcumin-treated pancreatic
cancer cells as observed by spectral studies and fluorescence microscopy.
Furthermore, curcumin is delivered to recipient pancreatic cancer cells via
exosomes, promoting cytotoxicity as demonstrated by Hoffman modulation contrast
microscopy as well as AlamarBlue and Trypan blue exclusion assays. Collectively,
these data suggest that the efficacy of curcumin may be enhanced in pancreatic
cancer cells through exosomal facilitation.
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