Recombinant human lactoferrin carrying humanized glycosylation exhibits antileukemia selective cytotoxicity, microfilament disruption, cell cycle arrest, and apoptosis activities

Nakamura-Bencomo, Sayuri I.; Gutierrez, Denisse A.; Robles-Escajeda, Elisa; Iglesias-Figueroa, Blanca Flor; Siqueiros-Cendón, Tania; Espinoza-Sánchez, Edward Alexander; Arévalo-Gallegos, Sigifredo; Aguilera, Renato J.; Rascón-Cruz, Quintín; Varela-Ramı́rez, Armando

doi:10.1007/s10637-020-01020-2

Cited by 23 publications

(19 citation statements)

References 74 publications

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“…Additionally, the extract was active against bacteria and yeast, and the obtained results suggest that antifungal mode of action is associated with disruption of cell membrane permeability. Previously, it was published that some natural products, like green barley extract [ 44 ], and lactoferrin [ 45 ] exhibited an antiproliferative activity on cancer cells, making our results in agreement with literature pointing to the anticancer effects of natural products. Altogether, the obtained results serve as a good basis for further research of the anti-glioblastoma and antimicrobial mechanisms of actions of herba Anthrisci cerefolii .…”

Section: Discussionsupporting

confidence: 92%

Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions

et al. 2021

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Anthriscus cerefolium (L.) Hoffm. is a plant traditionally used around the globe since antiquity. Although widely used in many traditional medicines in different cultures, from the scientific point of view it is poorly investigated. Glioblastoma, a tumor type with poor prognosis, is the most common and lethal brain tumor in adults. Current therapeutic strategies for glioblastoma include surgery, radiation and chemotherapy. On the other hand, it has been revealed that patients with cancers are highly susceptible to microbial infections due to the invasive nature of cancer treatment approaches. This study was designed to investigate the chemical profile of herba Anthriscii cerefoli methanolic extract by applying UHPLC-LTQ OrbiTrap MS4 analysis and to analyze its anti-glioblastoma and antimicrobial activities. This study revealed that methanolic extract of herba Anthrisc cerefolii contained phenolic acids and flavonoids, with 32 compounds being identified. Anti-glioblastoma activity was investigated in vitro using A172 glioblastoma cell line. The cytotoxic effects of the extract on A172 cells were compared to the same effect on primary human gingival fibroblast (HGF-1) cells. Decreased rate of proliferation and changes in cell morphology were detected upon treatment of A172 cells with the extract. The antimicrobial activity of extract was tested against Staphylococcus aureus and Candida species. The extract was active against the tested bacterium and yeasts, inhibiting free floating cells and microbial biofilms. This study is the first one to provide a detailed description of the chemical profile of A. cerefolium extract dealing with scientific insights into its anti-glioblastoma and antimicrobial activities.

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Section: Discussionsupporting

confidence: 92%

Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions

et al. 2021

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“…In addition, glycosylation has complex significance on the function of proteins. For example, N-glycosylation can increase protein stability [ 35 ]. The N-glycosylation of Asn-297 of murine IgG can enhance immune response.…”

Section: Discussionmentioning

confidence: 99%

“…Although this bacteria-heteroexpressed HSPB5 exerts chaperone activity, it cannot completely imitate the HSPB5 secreted by mammalian cells due to a lack of posttranslational modification [ 33 , 34 ]. Earlier, it has been reported that human recombinant lactoferrin, carrying a humanized glycosylation, displays selective antiproliferative effects on cancer cells [ 35 ]. This research suggests that natural recombinant proteins possess beneficial biological activities on human health.…”

Section: Introductionmentioning

confidence: 99%

The engineered expression of secreted HSPB5-Fc in CHO cells exhibits cytoprotection in vitro

Xue

et al. 2021

BMC Biotechnol

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Background HSPB5 is an ATP-independent molecular chaperone that is induced by heat shock or other proteotoxic stresses. HSPB5 is cytoprotective against stress both intracellularly and extracellularly. It acts as a potential therapeutic candidate in ischemia-reperfusion and neurodegenerative diseases. Results In this paper, we constructed a recombinant plasmid that expresses and extracellularly secrets a HSPB5-Fc fusion protein (sHSPB5-Fc) at 0.42 μg/ml in CHO-K1 cells. This sHSPB5-Fc protein contains a Fc-tag at the C-terminal extension of HSPB5, facilitating protein-affinity purification. Our study shows that sHSPB5-Fc inhibits heat-induced aggregation of citrate synthase in a time and dose dependent manner in vitro. Administration of sHSPB5-Fc protects lens epithelial cells against cisplatin- or UVB-induced cell apoptosis. It also decreases GFP-Httex1-Q74 insolubility, and reduces the size and cytotoxicity of GFP-Httex1-Q74 aggregates in PC-12 cells. Conclusion This recombinant sHSPB5-Fc exhibits chaperone activity to protect cells against proteotoxicity.

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“…On the other hand, it is known that many cancer cells have a high content of proteoglycan, glycosaminoglycan and sialic acid, which are known to interact with Lf, which probably activates other signaling pathways to generate harmful effects to cells [ 66 ]. This possible mechanism will also explain the high cytotoxic selectivity that Lf has on cancer cells and not on healthy cells [ 65 , 67 , 68 , 69 , 70 ]. Despite the fact that various authors showed that Lf has high selective cytotoxicity, not all reported the selective cytotoxicity index (SCI), which gives the ability of a compound to kill cancer cells with minimal toxicity to non-cancer cells.…”

Section: Anticancer Activitymentioning

confidence: 99%

“…Currently, treatments for different types of leukemia, including acute myeloid leukemia and acute lymphoid leukemia, improve the survival rate in diagnosed children; however, the long-term consequences can manifest as cardiovascular diseases that increase the risk of death [ 82 , 83 ]. In this sense, once again, Lf could be an alternative that minimizes side effects in patients, since it was shown to induce apoptosis in leukemia [ 70 , 84 ]. In the same way that Lf has been successfully tested for the treatment of cancers, primarily breast cancer, both Lf and bioactive Lf-derived peptides have been used successfully in the treatment of other types of cancer such as leukemia.…”

Section: Anticancer Activitymentioning

confidence: 99%

Lactoferrin: A Glycoprotein Involved in Immunomodulation, Anticancer, and Antimicrobial Processes

et al. 2021

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Lactoferrin is an iron binding glycoprotein with multiple roles in the body. Its participation in apoptotic processes in cancer cells, its ability to modulate various reactions of the immune system, and its activity against a broad spectrum of pathogenic microorganisms, including respiratory viruses, have made it a protein of broad interest in pharmaceutical and food research and industry. In this review, we have focused on describing the most important functions of lactoferrin and the possible mechanisms of action that lead to its function.

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Recombinant human lactoferrin carrying humanized glycosylation exhibits antileukemia selective cytotoxicity, microfilament disruption, cell cycle arrest, and apoptosis activities

Cited by 23 publications

References 74 publications

Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions

Extract of Herba Anthrisci cerefolii: Chemical Profiling and Insights into Its Anti-Glioblastoma and Antimicrobial Mechanism of Actions

The engineered expression of secreted HSPB5-Fc in CHO cells exhibits cytoprotection in vitro

Lactoferrin: A Glycoprotein Involved in Immunomodulation, Anticancer, and Antimicrobial Processes

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