Beneficial effect of silkworm hemolymph on a CHO cell system: Inhibition of apoptosis and increase of EPO production

Shin Sik Choi, Won Jong Rhee, Tai Hyun Park

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Abstract

To produce erythropoietin (EPO), Chinese hamster ovary (CHO) cells were first cultured in a medium containing FBS (growth medium) and then in a serum-free medium containing sodium butyrate (production medium). Sodium butyrate increases recombinant protein production, but also induces apoptosis, which reduces cell viability and productivity. In a previous study, we found that silkworm hemolymph (SH), an insect serum, inhibits the apoptosis of insect and mammalian cells. To overcome sodium butyrate-induced apoptosis, we added SH to growth medium. This pretreatment with SH inhibited the sodium butyrate-induced apoptosis of CHO cells and consequently increased their longevity and their ability to produce EPO. As a result, the volumetric productivity of EPO was increased five-fold. SH was found to inhibit cytochrome c release from mitochondria into the cytosol, and prevented the activation of caspase-3 and other subsequent caspase reactions.

Original languageEnglish
Pages (from-to)793-800
Number of pages8
JournalBiotechnology and Bioengineering
Volume91
Issue number7
DOIs
StatePublished - 30 Sep 2005

Keywords

  • Apoptosis
  • Chinese hamster ovary (CHO)
  • Erythropoietin (EPO)
  • Silkworm hemolymph (SH)
  • Sodium butyrate

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