Abstract
Lonidamine (LND), a selective inhibitor of the energy metabolism of tumor cells, induces apoptosis, independently of the p53 gene, in the adriamycin(ADR)-resistant MCF7 breast-cancer cell line (MCF7 ADR). On the contrary, LND fails to activate the apoptotic program in the parental MCF7- sensitive cell line (MCF7 WT). The extent of bcl-2 expression might account for the different effect of LND on these cell lines. In fact, the MCF7 ADR line shows a low level of bcl-2 protein, whereas MCF7 WT expresses a high level of bcl-2. We therefore investigated the relationship between the amount of bcl-2 and the ability of LND to induce apoptosis, using 4 clones over- expressing bcl-2. The effect of bcl-2 on the energy metabolism was also evaluated. We demonstrated that over-expression of bcl-2 inhibited LND- induced apoptosis, while reducing 14CO2 production, oxygen uptake and ATP content, whereas aerobic lactate production was essentially unaffected. In addition, LND decreased the oxidative metabolism of the MCF7 ADR cells to a greater extent than it did in the bcl-2 transfectants.
| Original language | English |
|---|---|
| Pages (from-to) | 125-130 |
| Number of pages | 6 |
| Journal | International Journal of Cancer |
| Volume | 82 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2 1999 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
bcl-2 Inhibits mitochondrial metabolism and lonidamine-induced apoptosis in adriamycin-resistant MCF7 cells. / Biroccio, Annamaria; Del Bufalo, Donatella; Fanciulli, Maurizio; Bruno, Tiziana; Zupi, Gabriella; Floridi, Aristide.
In: International Journal of Cancer, Vol. 82, No. 1, 02.07.1999, p. 125-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - bcl-2 Inhibits mitochondrial metabolism and lonidamine-induced apoptosis in adriamycin-resistant MCF7 cells
AU - Biroccio, Annamaria
AU - Del Bufalo, Donatella
AU - Fanciulli, Maurizio
AU - Bruno, Tiziana
AU - Zupi, Gabriella
AU - Floridi, Aristide
PY - 1999/7/2
Y1 - 1999/7/2
N2 - Lonidamine (LND), a selective inhibitor of the energy metabolism of tumor cells, induces apoptosis, independently of the p53 gene, in the adriamycin(ADR)-resistant MCF7 breast-cancer cell line (MCF7 ADR). On the contrary, LND fails to activate the apoptotic program in the parental MCF7- sensitive cell line (MCF7 WT). The extent of bcl-2 expression might account for the different effect of LND on these cell lines. In fact, the MCF7 ADR line shows a low level of bcl-2 protein, whereas MCF7 WT expresses a high level of bcl-2. We therefore investigated the relationship between the amount of bcl-2 and the ability of LND to induce apoptosis, using 4 clones over- expressing bcl-2. The effect of bcl-2 on the energy metabolism was also evaluated. We demonstrated that over-expression of bcl-2 inhibited LND- induced apoptosis, while reducing 14CO2 production, oxygen uptake and ATP content, whereas aerobic lactate production was essentially unaffected. In addition, LND decreased the oxidative metabolism of the MCF7 ADR cells to a greater extent than it did in the bcl-2 transfectants.
AB - Lonidamine (LND), a selective inhibitor of the energy metabolism of tumor cells, induces apoptosis, independently of the p53 gene, in the adriamycin(ADR)-resistant MCF7 breast-cancer cell line (MCF7 ADR). On the contrary, LND fails to activate the apoptotic program in the parental MCF7- sensitive cell line (MCF7 WT). The extent of bcl-2 expression might account for the different effect of LND on these cell lines. In fact, the MCF7 ADR line shows a low level of bcl-2 protein, whereas MCF7 WT expresses a high level of bcl-2. We therefore investigated the relationship between the amount of bcl-2 and the ability of LND to induce apoptosis, using 4 clones over- expressing bcl-2. The effect of bcl-2 on the energy metabolism was also evaluated. We demonstrated that over-expression of bcl-2 inhibited LND- induced apoptosis, while reducing 14CO2 production, oxygen uptake and ATP content, whereas aerobic lactate production was essentially unaffected. In addition, LND decreased the oxidative metabolism of the MCF7 ADR cells to a greater extent than it did in the bcl-2 transfectants.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033516635&partnerID=8YFLogxK
U2 - 10.1002/(SICI)1097-0215(19990702)82:1<125::AID-IJC21>3.0.CO;2-Q
DO - 10.1002/(SICI)1097-0215(19990702)82:1<125::AID-IJC21>3.0.CO;2-Q
M3 - Article
C2 - 10360831
AN - SCOPUS:0033516635
VL - 82
SP - 125
EP - 130
JO - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 1
ER -