Caspases as a Target for Apoptosis Inhibition in Hybridoma Cells in Culture

Gabernet, C.; Tintó, Albert; Vives, Joaquim; Prats, Eva; Cornudella, L.; Cairó, Jordi J.; Gòdia, Francesc

doi:10.1007/0-306-46875-1_30

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“…Z-VAD, a highly cell permeable and irreversible broad-spectrum caspase inhibitor (Lemaire et al, 1998), was shown to only slightly antagonize dexrazoxane-induced apoptosis in CC9C10 hybridomas (Figure 6A). This result is consistent with the antiapoptotic effects of Z-VAD in a hybridoma cell line deprived of glutamine (Gabernet et al, 1999). Z-Asp, another broad spectrum caspase inhibitor (Mashima et al, 1995), did not antagonize dexrazoxane-induced apoptosis in CC9C10 cells (Figure 6B).…”

Section: Discussionsupporting

confidence: 86%

“…The low levels of apoptosis after the end of exponential growth in control cells, as evidenced by both methods of detection, was likely due to nutrient limitation (i.e. glucose or glutamine) in the culture medium as we have previously shown in the CC9C10 cell line (Barnabé, 1998), and has been shown in cells of lymphoid origin (Gabernet et al, 1999;Mercille and Massie, 1994;Petronini et al, 1996).…”

Section: Discussionsupporting

confidence: 59%

“…Thus, we hypothesized that the caspase inhibitors, Z-VAD and Z-Asp, might be able to inhibit apoptosis. It was previously shown (Gabernet et al, 1999) that Z-VAD inhibited apoptosis in hybridomas. Likewise, Z-Asp was shown to inhibit dexrazoxane-induced apoptosis in human leukemic CEM cells (Khelifa and Beck, 1999).…”

Section: Inhibition Of Dexrazoxane-induced Apoptosis By Caspase Inhibitorsmentioning

confidence: 91%

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2001

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The effect of dexrazoxane on monoclonal antibody (Mab) production by CC9C10 hybridoma cells was investigated. Dexrazoxane is a catalytic inhibitor of DNA topoisomerase II. DNA topoisomerase II has a critical role in DNA metabolism and its inhibition by dexrazoxane can prevent completion of cytokinesis. Incubation of hybridomas with dexrazoxane was found to increase specific monoclonal antibody production by up to four-fold. However, due to the growth inhibitory effects of dexrazoxane the total Mab yield decreased by 40%. Under high density culture conditions(defined here as 10(6) cells ml(-1)) specific monoclonal antibody production increased by up to 37%, which was, however, accompanied by up to a 48% decrease in Mab yield. Hybridomasthat were incubated with dexrazoxane significantly increased in size due to the inhibition of cytokinesis. Dexrazoxane was also observed to induce a delayed apoptosis in the hybridomas. The caspase inhibitor Z-VAD-fmk slightly decreased the apoptotic effects of dexrazoxane. Preincubation with the caspase inhibitorZ-Asp-CH2-DCB had no effect on dexrazoxane-treated hybridomas, but it did have antiapoptotic effects on the untreated hybridomas which normally undergo a significant basal level of apoptosis. In conclusion, dexrazoxane-induced growth inhibition (which results in higher specific antibody production) and apoptosis inhibition (which results in prolonged viability) has the potential to significantly enhance the productivity of hybridoma cell cultures.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionsupporting

confidence: 59%