A Novel Human Recombinant Lactoferrin Inhibits Lung Adenocarcinoma Cell Growth and Migration with No Cytotoxic Effect on Normal Human Epithelial Cells.
Apoptosis
Glycosylation
Lung cancer
Recombinant human lactoferrin
Journal
Archivum immunologiae et therapiae experimentalis
ISSN: 1661-4917
Titre abrégé: Arch Immunol Ther Exp (Warsz)
Pays: Switzerland
ID NLM: 0114365
Informations de publication
Date de publication:
08 Nov 2021
08 Nov 2021
Historique:
received:
18
06
2021
accepted:
29
09
2021
entrez:
8
11
2021
pubmed:
9
11
2021
medline:
14
1
2022
Statut:
epublish
Résumé
Lung cancer remains the leading cause of cancer death worldwide. Despite the recent advances in cancer treatment, only a subset of patients responds to targeted and immune therapies, and many patients developing resistance after an initial response. Lactoferrin (Lf) is a natural glycoprotein with immunomodulatory and anticancer activities. We produced a novel recombinant human Lf (rhLf) that exhibits glycosylation profile compatible with the natural hLf for potential parenteral therapeutic applications. The aim of this study was to evaluate the anticancer effects of this novel rhLf in human lung adenocarcinoma cells and its mechanisms of action. The results showed a concentration-dependent inhibition of A549 cancer cell growth in response to rhLf. Treatment with 1 mg/ml of rhLf for 24 h and 72 h resulted in a significant inhibition of cancer cell growth by 32% and 25%, respectively. Moreover, rhLf increased fourfold the percentage of early and late apoptotic cells compared to the control. This effect was accompanied by increased levels of caspase-3 activity and cell cycle arrest at the S phase in rhLf-treated cancer cells. Furthermore, rhLf significantly attenuated A549 cell migration. Importantly, treatment of normal human bronchial epithelial (NHBE) cells with rhLf showed the cell viability and morphology comparable to the control. In contrast, chemotherapeutic etoposide induced cytotoxicity in NHBE cells and reduced the cell viability by 40%. These results demonstrate the selective anticancer effects of rhLf against lung adenocarcinoma cells without cytotoxicity on normal human cells. This study highlights a potential for clinical utility of this novel rhLf in patients with lung cancer.
Identifiants
pubmed: 34748082
doi: 10.1007/s00005-021-00637-2
pii: 10.1007/s00005-021-00637-2
pmc: PMC8575758
doi:
Substances chimiques
Recombinant Proteins
0
Lactoferrin
EC 3.4.21.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
33Subventions
Organisme : uniwersytet medyczny w lodzi
ID : 503/3-015-01/503-31-001-19-00
Organisme : uniwersytet medyczny w lodzi
ID : 501/3-015-01/501-71-291
Organisme : pharmareview corporation, houston, texas
ID : ID/PRC 27/09/2018
Informations de copyright
© 2021. The Author(s).
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