title: Valeric acid induces cell cycle arrest at G1 phase in CHO cell cultures and improves recombinant antibody productivity.
abstract: To find a more effective chemical reagent for improved monoclonal antibody (mAb) production, eight chemical reagents (curcumin, quercein, DL-sulforaphane, thymidine, valeric acid, phenyl butyrate, valproic acid, and lithium chloride) known to induce cell cycle arrest were examined individually as chemical additives to recombinant CHO (rCHO) cell cultures producing mAb. Among these chemical additives, valeric acid showed the best production performance. Valeric acid decreased specific growth rate (μ), but increased culture longevity and specific mAb productivity (qmAb ) in a dose-dependent manner. The beneficial effect of valeric acid on culture longevity and qmAb outweighed its detrimental effect on μ, resulting in 2.9-fold increase in the maximum mAb concentration when 1.5 mM valeric acid was added to the cultures. Furthermore, valeric acid did not negatively affect the mAb quality attributes with regard to aggregation, charge variation, and galactosylation. Unexpectedly, galactosylation of the mAb increased by the 1.5 mM valeric acid addition. Taken together, the results obtained here demonstrate that valeric acid is an effective chemical reagent to increase mAb production in rCHO cells.
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
authors.forename: Jin Hyoung
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Republic of Korea.
authors.forename: Soo Min
authors.initials: SM
authors.lastname: Noh
authors.affiliation: New Drug Development Center, Cheongju, Republic of Korea.
authors.forename: Ju Rang
authors.initials: JR
authors.lastname: Woo
authors.affiliation: New Drug Development Center, Cheongju, Republic of Korea.
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Biological Sciences, KAIST, Daejeon, Republic of Korea. gyunminlee@kaist.ac.kr.
authors.forename: Gyun Min
authors.initials: GM
authors.lastname: Lee
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells / Q000166:cytology / Q000187:drug effects*; D018929:Cell Culture Techniques / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D003470:Culture Media / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D059585:G1 Phase Cell Cycle Checkpoints; D005690:Galactose / Q000378:metabolism; D006031:Glycosylation; D010421:Pentanoic Acids / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D003470:Culture Media; D010421:Pentanoic Acids; D011994:Recombinant Proteins; C038780:n-pentanoic acid; D005690:Galactose
keywords: Cell cycle; Chinese hamster ovary cell; Galactosylation; Specific productivity; Valeric acid