Growth inhibition of breast cancer cells induced by exogenous ATP

Abstract

Addition of ATP (> 0.1 mM) to cultures of human breast cancer T47D cells resulted in an inhibition of cell proliferation. The inhibition was found to be specific for ATP, and dependent on its concentration. Growth inhibition continued for at least three days, although ATP and its hydrolysis products were metabolized within one day. Conditioned medium from ATP-treated cultures (CM+) was found to inhibit the growth of cells that were not exposed to ATP. This is an indication that extracellular factors, besides ATP, are involved in the inhibition process. The inhibition was maintained after dialysis of the CM+, using an 8 kDa cut-off membrane. Conditioned medium from untreated cultures (CM-), however, only slightly affected cell growth. The data suggest that the CM(+)-induced cell growth inhibition is mediated by an ATP-activated growth inhibiting factor. Flow microfluorometry and thymidine incorporation experiments have shown that the growth arrest is mainly due to the elongation of the S-phase of the cell cycle.

Extracellular nucleotides stimulate proliferation in MCF-7 breast cancer cells via P2-purinoceptors

“…P2T (P2Y3) purinoceptors, respectively, for which these nucleotides are agonists (Barnard et al, 1994 (Batra and Fadeel, 1994). Similarly high concentrations of ATP were reported to induce growth inhibition in two breast cancer cell lines, T47-D (Spungin and Friedberg, 1993) and that used here, MCF-7 (Vandewalle et al, 1994). The mechanism underlying this inhibition is not fully understood.…”

“…The mechanism underlying this inhibition is not fully understood. Some investigators have attributed inhibition to adenosine following the sequential dephosphorylation of ATP (Spungin and Friedberg, 1993;Lasso de la Vega et al, 1994), whereas others have invoked P2Z purinoceptormediated cell permeabilization (Rapaport, 1990;Dubyak and ElMoatassim, 1993). Considering the high concentrations of ATP required to achieve this effect, its physiological relevance is questionable.…”

Purinergic signaling inhibits human acute myeloblastic leukemia cell proliferation, migration, and engraftment in immunodeficient mice

“…37 Several clinical applications of extracellular ATP and adenosine have been reported in many fields, including oncology, 38-42 and several mechanisms have been proposed as being responsible for the effects of ATP in cancer. [43][44][45][46] In the present study, 1mM ATP decreased AML proliferation with lower effects on apoptotic death, which was readily appreciable at 5mM perhaps because of the unregulated opening of membrane P2X pores (data not shown). No effects were seen on normal CD34 ϩ cells.…”

Growth inhibition of lung cancer cells by adenosine 5′‐triphosphate

“…These effects were not observed in untransformed control cells [Hatta et al, 1993[Hatta et al, , 1994Kitagawa et al, 1988;Mure et al, 1992;Rapaport, 1983]. In human tumor cell lines, ATP inhibited the growth of pancreatic adenocarcinoma cells [Rapaport, 1983], colon adenocarcinoma cells [Rapaport, 1983], melanoma cells [Kitagawa et al, 1988;Rapaport, 1983], androgenindependent prostate carcinoma cells [Fang et al, 1992], breast cancer cells [Abraham et al, 1996;Spungin and Friedberg, 1993;Vandewalle et al, 1994], myeloid and monocytic leukemia cells [Hatta et al, 1994], and multidrug resistant colon carcinoma cells [Correale et al, 1995]. In rats and mice, ATP was found to inhibit the growth of lymphomas [Nayak et al, 1990], colon carcinomas [Rapaport and Fontaine, 1989], fibrosarcomas [Froio et al, 1995], Ehrlich ascites tumors [Lasso de la Vega et al, 1994], and breast tumors [Abraham et al, 1996].…”

“…Box 616, 6200 MD Maastricht, The Netherlands. E-mail: Dagnelie@epid.unimaas.nl concentration below 50 mM [Huang et al, 1991;Wang et al, 1992], whereas higher ATP concentrations inhibited growth [Belzer and Friedberg, 1989;Chahwala and Cantley, 1984;Fang et al, 1992;Hatta et al, 1994;Rapaport, 1983;Rapaport et al, 1983;Seetulsingh-Goorah and Stewart, 1998;Spungin and Friedberg, 1993;Vandewalle et al, 1994]. These effects were not observed in untransformed control cells [Hatta et al, 1993[Hatta et al, , 1994Kitagawa et al, 1988;Mure et al, 1992;Rapaport, 1983].…”