Page 14 - Read Online

J Cancer Metastasis Treat 2019;5:5 I http://dx.doi.org/10.20517/2394-4722.2018.108 Page 9 of 27

12. The role of diet related short chain fatty acid acetate in colorectal cancer: therapeutic
implications

Ana Preto

Centre of Molecular and Environmental Biology (CBMA), Department of Biology, School of Sciences, University
of Minho, Braga 4710-057, Portugal.

Colorectal cancer (CRC) is an important public health concern worldwide, particularly among populations
that adopt Western-style diets. The use of dietary propionibacteria found in dairy products, which produce
short-chain fatty acids (SCFA), has been suggested as a possible strategy in the prevention and therapy of
CRC. The SCFA acetate has been proved by us and others to induce apoptosis in CRC cells. Our group has
been focusing on unravelling the mechanisms underlying acetate-induced apoptosis and on understanding
the precise role of acetate in CRC cells.

We showed that acetate induces partial lysosome membrane permeabilization with specific cathepsin
D (CatD) release to the cytosol in CRC cells. We verified that CatD has an anti-apoptotic role by the
degradation of damaged mitochondria when autophagy is impaired, protecting CRC cells from acetate-
induced apoptosis. Moreover, we demonstrated that acetate enters CRC cells by a sodium dependent
monocarboxylate transporter 1 and passive diffusion by aquaporins. We also found that MCT-1 and/or
MCT-2 seems to mediate acetate transport in CRC cells exposed to acetate. Additionally, we observed that
acetate upregulates MCTs expression and promotes plasma membrane re-localization of MCT-1 and triggers
changes in glucose metabolism. Further, we explored the combined treatment of acetate with the glycolysis
inhibitor 3BP and we demonstrated that 3BP potentiates acetate-induced apoptosis in CRC cells.

Our results established a protective role of CatD in acetate-induced apoptosis which could negatively impact
the efficacy of acetate. Thus, the use of CatD inhibitors in combination with strategies to increase acetate
concentrations in the colon, like nutraceuticals, should be explored. Our findings also support a novel
approach for CRC therapy based on the association of acetate with 3BP or other anti-cancer agents whose
transport is mediated by MCTs.

13. Implementing new diet formulations in order to shape microbiota and reverse
chemoresistance in the frame of pancreatic cancer

Valerio Pazienza, Concetta Panebianco, Kaarel Adamberg, Vilu Raivo, Madis Jaagura, Chiara
Saracino, Signe Adamberg, Anna Grazia Di Chio

Gastroenterology Unit IRCCS “Casa Sollievo della Sofferenza” Hospital San Giovanni Rotondo, Foggia 71013, Italy.

Introduction: Despite recent advances in treatment options, pancreatic cancer (PC) remain a highly
malignant disease and due to its poor prognosis it is ranked as the fourth leading cause of cancer-related
deaths worldwide. We have previously demonstrated that manipulating the dietary intake of total amount
of calories (using a short-term fasting cycles approach) or replacing carbohydrate with resistant starch have
the potential to improve the efficacy of chemotherapy against PC. The aim of this talk is to clarify the effect
of the engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the
composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft
model. Moreover we will shed light on the interaction between the microbiota and chemotherapeutic drugs.