Auto-antibodies against apolipoprotein A-1 block cancer cells proliferation and induce apoptosis
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Nathalie Satta1,2, Rémy Weppe1,2, Sabrina Pagano1,2, Miguel Frias1,2, Catherine Juillard1,2 and Nicolas Vuilleumier1,2
1 Division of Laboratory Medicine, Department of Diagnostic, Geneva University Hospitals, Geneva, Switzerland
2 Department of Medicine, Medical Faculty, Geneva University, Geneva, Switzerland
Keywords: anti-apoA-1 antibodies; apoptose; cell proliferation; oxidative stress
Received: July 03, 2020 Accepted: October 27, 2020 Published: November 17, 2020
Auto-antibodies against apoA-1 (anti-apoA-1 IgGs) have been identified as important actors of atherosclerosis development through pro-inflammatory and pro-atherogenic properties and to also induce apoptosis in tumoral neuronal and lymphocyte derived cell lines through unknown mechanisms. The purpose of this study was to explore the cellular pathways involved in tumoral cell survival modulated by anti-apoA-1 antibodies. We observed that anti-apoA-1 antibodies induce growth arrest (in G2/M phase) and cell apoptosis through caspase 3 activation, accompanied by a selective p53 phosphorylation on serine 15. RNA sequencing indicated that anti-apoA-1 IgGs affect the expression of more than 950 genes belonging to five major groups of genes and respectively involved in i) cell proliferation inhibition, ii) p53 stabilisation and regulation, iii) apoptosis regulation, iv) inflammation regulation, and v) oxidative stress.
In conclusion, anti-apoA-1 antibodies seem to have a role in blocking tumoral cell proliferation and survival, by activating a major tumor suppressor protein and by modulating the inflammatory and oxidative stress response. Further investigations are needed to explore a possible anti-cancer therapeutic approach of these antibodies in very specific and circumscribed conditions.
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