Improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells

Razaghi, Ali, Villacrés, Carina, Jung, Vincent, Mashkour, Narges, Butler, Michael, Owens, Leigh, and Heimann, Kirsten (2017) Improved therapeutic efficacy of mammalian expressed-recombinant interferon gamma against ovarian cancer cells. Experimental Cell Research, 359 (1). pp. 20-29.

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Abstract

Human interferon gamma (hIFNγ) affects tumour cells and modulates immune responses, showing promise as an anti-cancer biotherapeutic. This study investigated the effect of glycosylation and expression system of recombinant hIFNγ in ovarian carcinoma cell lines, PEO1 and SKOV3. The efficacy of E. coli- and mammalian-expressed hIFNγ (hIFNγ-CHO and HEK293, glycosylated/de-glycosylated) on cytostasis, cell death (MTT, and Guava-ViaCount® flow-cytometry) and apoptotic signalling (Western blot of Cdk2, histone H3, procaspase-3, FADD, cleaved PARP, and caspase-3) was examined. Hydrophilic Interaction Liquid Chromatography determined the structure of N-linked glycans present in HEK293-expressed hIFNγ (hIFNγ-HEK). PEO1 was more sensitive to hIFNγ than SKOV3, but responses were dose-dependent and expression platform/glycosylation status-independent, whereas SKOV3 responded to mammalian-expressed hIFNγ in a dose-independent manner, only. Complex-type oligosaccharides dominated the N-glycosylation pattern of hIFNγ-HEK with some terminal sialylation and core fucosylation. Cleaved PARP and cleaved caspase-3 were not detected in either cell line, but FADD was expressed in SKOV3 with levels increased following treatment. In conclusion, hIFNγ did not induce apoptosis in either cell line. Mammalian- expressed hIFNγ increased cell death in the drug-resistant SKOV3. The presence of FADD in SKOV3, which may inhibit apoptosis through activation of NF-κB, could serve as a novel therapeutic target.

Item ID: 50147
Item Type: Article (Research - C1)
ISSN: 1090-2422
Keywords: interferon gamma, glycosylation, ovarian cancer, SKOV3, FADD, therapeutic efficacy
Funders: James Cook University (JCU), Higher Degree Research Scheme
Projects and Grants: JCU Postgraduate Research Scholarship
Date Deposited: 15 Sep 2017 05:37
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111201 Cancer Cell Biology @ 60%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111204 Cancer Therapy (excl Chemotherapy and Radiation Therapy) @ 30%
11 MEDICAL AND HEALTH SCIENCES > 1112 Oncology and Carcinogenesis > 111207 Molecular Targets @ 10%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920102 Cancer and Related Disorders @ 40%
86 MANUFACTURING > 8608 Human Pharmaceutical Products > 860803 Human Pharmaceutical Treatments (e.g. Antibiotics) @ 60%
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