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J Cancer Metastasis Treat 2019;5:31 I http://dx.doi.org/10.20517/2394-4722.2019.21 Page 26 of 36

skeletal muscle of both C26 and C26 OXFU animals, mitochondrial markers such as PGC-1α, cytochrome
c and SDHA were reduced and these alterations were not corrected by SS-31. In the C26 OXFU mice the
reduced expression of mitochondrial markers was also associated with impaired muscle oxidative capacity
and ATP content. These latter were improved by SS-31 in the C26 hosts but not in the C26 OXFU mice.
Muscle wasting and mitochondrial impairments were associated with reduced protein synthesis in the
C26 hosts. Consistently with improved muscle energetics, SS-31 administration partially corrected muscle
protein synthesis in C26-bearing mice.

Overall, SS-31 administration could contribute to correct muscle wasting and to improve muscle energetics
in tumor-bearing animals, suggesting that targeting mitochondria could be part of a multimodal therapy
against cancer cachexia. In order to increase the translational value of the results, further analysis and
treatment optimization are needed in order to demonstrate the effectiveness of SS-31 in C26-bearing mice
treated with chemotherapy.

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33. Resveratrol counteracts the pro-invasive activity of lysophosphatidic acid in ovarian cancer

cells by rescuing autophagy and down-regulating the hedgehog pathway

1
1
1
2
1
Alessandra Ferraresi , Christian Seca , Suyanee Thongchot , Letizia Vallino , Giovanna Chiorino , Danny N.
Dhanasekaran , Ciro Isidoro 1
3
1 Laboratory of Molecular Pathology and Nanobioimaging, Department of Health Sciences, Università del
Piemonte Orientale “A. Avogadro”, Novara 28100, Italy.
2 Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia, Biella 13900, Italy.
3 Stephenson Cancer Center and Department of Cell Biology, The University of Oklahoma Health Sciences
Center, Oklahoma City, OK 73104, USA.

Ovarian cancer emerges as a highly aggressive metastatic disease characterized by a high grade of lethality
and it remains the most lethal gynecologic cancer with a five-year survival rate of about 30%-40%. Cancer
progression is facilitated by pro-invasive factors released by the tumour microenvironment and modulating
the epithelial-to-mesenchymal transition (EMT).

Lysophosphatidic acid (LPA), a bioactive phospholipid highly secreted in the ascitic fluid and plasma of
ovarian cancer patients, stimulates the growth and promotes the tissue invasion of cancer cells. Resveratrol
(RV), a polyphenol found in grapes and in a variety of natural products, is attracting the interest of many
researchers thank to its several anti-cancer properties.

Here we show that LPA induces the EMT through induction of the Hedgehog pathway and concomitant
inhibition of autophagy in the cancer cells at the migration front. We found that RV and LPA regulate in an