Genes & Cancer

Docosahexaenoic acid (DHA) promotes immunogenic apoptosis in human multiple myeloma cells, induces autophagy and inhibits STAT3 in both tumor and dendritic cells

Donatella D’Eliseo1,4, Livia Di Renzo2, Angela Santoni1,3 and Francesca Velotti4

1 Department of Molecular Medicine, Pasteur Italia Laboratory, Rome, Italy

2 Department of Experimental Medicine, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Rome

3 IRCCS Neuromed, Pozzilli, IS, Italy

4 Department of Ecological and Biological Sciences (DEB), La Tuscia University, Largo dell’Università, Viterbo, Italy


Francesca Velotti, email:

Keywords: docosahexaenoic acid-DHA, immunogenic cell death, autophagy, STAT3, dendritic cells-DCs

Received: November 30, 2016 Accepted: February 19, 2017 Published: February 22, 2017


Docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid found in fish oil, is a multi-target agent and exerts anti-inflammatory and anticancer activities alone or in combination with chemotherapies. Combinatorial anticancer therapies, which induce immunogenic apoptosis, autophagy and STAT3 inhibition have been proposed for long-term therapeutic success. Here, we found that DHA promoted immunogenic apoptosis in multiple myeloma (MM) cells, with no toxicity on PBMCs and DCs. Immunogenic apoptosis was shown by the emission of specific DAMPs (CRT, HSP90, HMGB1) by apoptotic MM cells and the activation of their pro-apoptotic autophagy. Moreover, immunogenic apoptosis was directly shown by the activation of DCs by DHA-induced apoptotic MM cells. Furthermore, we provided the first evidence that DHA activated autophagy in PBMCs and DCs, thus potentially acting as immune stimulator and enhancing processing and presentation of tumor antigens by DCs. Finally, we found that DHA inhibited STAT3 in MM cells. STAT3 pathway, essential for MM survival, contributed to cancer cell apoptosis by DHA. We also found that DHA inhibited STAT3 in blood immune cells and counteracted STAT3 activation by tumor cell-released factors in PBMCs and DCs, suggesting the potential enhancement of the anti-tumor function of multiple immune cells and, in particular, that of DCs.

PII: 131