Chemotherapy induces ATP release from tumor cells.
Chemotherapy can induce anticancer immune responses. In contrast to a widely extended prejudice, apoptotic cell death is often more efficient in eliciting a protective anticancer immune response than necrotic cell death. Recently, we have found that purinergic receptors of the P2X7 type are required for the anticancer immune response induced by chemotherapy. ATP is the endogenous ligand that has the highest affinity for P2X7. Therefore, we investigated the capacity of a panel of chemotherapeutic agents to induce ATP release from cancer cells. Here, we describe that multiple distinct anticancer drugs reduce the intracellular concentration of ATP before and during the manifestation of apoptotic characteristics such as the dissipation of the mitochondrial transmembrane potential and the exposure of phosphatidylserine residues on the plasma membrane. Indeed, as apoptosis progresses, intracellular ATP concentrations decrease, although even advanced-stage apoptotic cells still contain sizeable ATP levels. Only when cells enter secondary necrosis, the ATP concentration falls to undetectable levels. Concomitantly, a wide range of chemotherapeutic agents causes the release of ATP into the extracellular space as they induce tumor cell death. Hence, ATP release is a general correlate of apoptotic cell death induced by conventional anticancer therapies.
INSERM, U848, Villejuif, France; Institut Gustave Roussy, Villejuif, France.
Isabelle
I
Martins
Antoine
A
Tesniere
Oliver
O
Kepp
Mickael
M
Michaud
Frederic
F
Schlemmer
Laura
L
Senovilla
Claire
C
Séror
Didier
D
Métivier
Jean-Luc
JL
Perfettini
Laurence
L
Zitvogel
Guido
G
Kroemer
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D005047:Etoposide / Q000494:pharmacology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D051379:Mice; D016685:Mitomycin / Q000494:pharmacology; D008942:Mitoxantrone / Q000494:pharmacology; D009369:Neoplasms / Q000188:drug therapy*; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology
D000970:Antineoplastic Agents; C064769:N-acetylsphingosine; D009944:Organoplatinum Compounds; D002104:Cadmium; D000077150:Oxaliplatin; D016685:Mitomycin; D019284:Thapsigargin; D005047:Etoposide; D000255:Adenosine Triphosphate; D008942:Mitoxantrone; D013110:Sphingosine; D002945:Cisplatin