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1.
Biosci Rep ; 41(12)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1592575

ABSTRACT

Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS). Additionally, one region from loop 1 of HCoV-229E, Loop1-HCoV-229E, was also synthesized and characterized. The A4W-GGN5 anticancer peptide and 5-fluorouracil (5-FU) were taken as a control in all experiments. Circular dichroism revealed an α-helix structure for the peptides derived from PS2Aa1 (P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa) and ß-laminar structure for the peptide derived from Alphacoronavirus spike protein Loop1-HCoV-229E. Peptides showed a hemolysis percentage of less than 20% at 100 µM concentration. Besides, peptides exhibited stronger anticancer activity against SW480 and SW620 cells after exposure for 48 h. Likewise, these compounds showed significantly lower toxicity against normal cells CHO-K1. The results suggest that native peptide fragments from Ps2Aa1 may be optimized as a novel potential cancer-therapeutic agents.


Subject(s)
Antineoplastic Agents/pharmacology , Colorectal Neoplasms/drug therapy , Endotoxins/pharmacology , Peptide Fragments/pharmacology , Spike Glycoprotein, Coronavirus/pharmacology , Alphacoronavirus , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , CD13 Antigens/metabolism , CHO Cells , Cell Line, Tumor , Cell Proliferation/drug effects , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cricetulus , Endotoxins/toxicity , Hemolysis/drug effects , Humans , Molecular Docking Simulation , Peptide Fragments/chemical synthesis , Peptide Fragments/toxicity , Protein Conformation, alpha-Helical , Sheep, Domestic , Spike Glycoprotein, Coronavirus/toxicity , Structure-Activity Relationship
2.
Biosci Rep ; 41(12)2021 12 22.
Article in English | MEDLINE | ID: covidwho-1526113

ABSTRACT

Parasporin-2Aa1 (PS2Aa1) is a toxic protein of 37 KDa (30 kDa, activated form produced by proteolysis) that was shown to be cytotoxic against specific human cancer cells, although its mechanism of action has not been elucidated yet. In order to study the role of some native peptide fragments of proteins on anticancer activity, here we investigated the cytotoxic effect of peptide fragments from domain-1 of PS2Aa1 and one of the loops present in the binding region of the virus spike protein from Alphacoronavirus (HCoV-229E), the latter according to scientific reports, who showed interaction with the human APN (h-APN) receptor, evidence corroborated through computational simulations, and thus being possible active against colon cancer cells. Peptides namely P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa were synthesized using the Fmoc solid-phase synthesis and characterized by mass spectrometry (MS). Additionally, one region from loop 1 of HCoV-229E, Loop1-HCoV-229E, was also synthesized and characterized. The A4W-GGN5 anticancer peptide and 5-fluorouracil (5-FU) were taken as a control in all experiments. Circular dichroism revealed an α-helix structure for the peptides derived from PS2Aa1 (P264-G274, Loop1-PS2Aa, and Loop2-PS2Aa) and ß-laminar structure for the peptide derived from Alphacoronavirus spike protein Loop1-HCoV-229E. Peptides showed a hemolysis percentage of less than 20% at 100 µM concentration. Besides, peptides exhibited stronger anticancer activity against SW480 and SW620 cells after exposure for 48 h. Likewise, these compounds showed significantly lower toxicity against normal cells CHO-K1. The results suggest that native peptide fragments from Ps2Aa1 may be optimized as a novel potential cancer-therapeutic agents.


Subject(s)
Antineoplastic Agents/pharmacology , Colorectal Neoplasms/drug therapy , Endotoxins/pharmacology , Peptide Fragments/pharmacology , Spike Glycoprotein, Coronavirus/pharmacology , Alphacoronavirus , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , CD13 Antigens/metabolism , CHO Cells , Cell Line, Tumor , Cell Proliferation/drug effects , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Cricetulus , Endotoxins/toxicity , Hemolysis/drug effects , Humans , Molecular Docking Simulation , Peptide Fragments/chemical synthesis , Peptide Fragments/toxicity , Protein Conformation, alpha-Helical , Sheep, Domestic , Spike Glycoprotein, Coronavirus/toxicity , Structure-Activity Relationship
4.
Clin J Oncol Nurs ; 25(2): 151-156, 2021 Apr 01.
Article in English | MEDLINE | ID: covidwho-1190123

ABSTRACT

BACKGROUND: Many hazardous drugs (HDs) are excreted in urine and feces, and evidence has shown that bathrooms of patients receiving chemotherapy at home are contaminated with HDs. However, little information exists on bathroom contamination in ambulatory clinics where HDs are administered. OBJECTIVES: This project aimed to determine the presence of HD residue in the patient and staff bathrooms of an ambulatory cancer center. METHODS: A quality improvement project was initiated to examine potential contamination by the HDs 5-fluorouracil and oxaliplatin in a patient bathroom and a secured badge-access staff bathroom in the infusion department of an ambulatory comprehensive cancer center. Twice-daily wipe testing was conducted on the floor in front of the toilet and the flush handle for five consecutive days. FINDINGS: Sixty-five percent of the samples from the floor of the patient bathroom were positive for at least one of the HDs. In the staff bathroom, 35% of the floor samples were positive for at least one HD. None of the flush handle samples were above the level of detection.


Subject(s)
Antineoplastic Agents , Neoplasms , Antineoplastic Agents/toxicity , Drug Contamination , Fluorouracil/toxicity , Humans , Neoplasms/drug therapy , Oxaliplatin/toxicity , Toilet Facilities
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