Ja. Zanghi et al., The growth factor inhibitor suramin reduces apoptosis and cell aggregationin protein-free CHO cell batch cultures, BIOTECH PR, 16(3), 2000, pp. 319-325
We have previously shown that Chinese hamster ovary (CHO) cells capable of
growing in medium free of exogenous proteins die by apoptosis during all st
ages of a batch culture (Zanghi et al., 1999). On the basis of the hypothes
is that extracellular death factors might be important in apoptosis under t
hese conditions, we examined the effect of the growth factor inhibitor and
antitumor agent suramin on CHO cell growth and apoptosis in serum-free cult
ure. Suramin protected against apoptosis during exponential growth, as indi
cated by the absence of DNA laddering and an increase in cell viability fro
m roughly 70% to above 95%. Suramin also effectively dispersed cell aggrega
tes so that single-cell suspension culture was possible. However, suramin d
id not protect; against apoptosis during the death phase, in contrast to se
rum, suggesting that antiapoptotic factors in the serum remain to be discov
ered. The increased viable cell yield following suramin supplementation res
ulted in a 40% increase in product yield, based on results with cells expre
ssing recombinant secreted alkaline phosphatase. Polysulfated compounds dex
tran sulfate and polyvinyl sulfate worked nearly as well as suramin in disp
ersing cell clumps and increasing viable cell yield, which implies that sur
amin's high sulfate group density may be responsible for its effects in cel
l culture. In addition, suramin was beneficial for long-term adaptation of
CHO cells to protein-free media suspension culture, and the compound was sy
nergistic with insulin in accelerating this adaptation time.