LE3 .A278 2020

2020

Coombs, Melanie

Acadia University

Bachelor of Science

Honours

Biology

Biology

This study investigates the anti-cancer effects of Mastoparan and its derivatives on the HCT-116 colon cancer cell line in vitro. Anti-cancer peptides are small peptides that exhibit increased toxicity towards cancer cells. Mastoparan is an amidated venom peptide extracted from the wasp species Vespula lewisii. Mastoparan acts as a broad-spectrum anti-cancer peptide that show increased toxicity towards cancer cells compared to normal cells. Four derivatives based on a single amino acid change from the parent peptide have been made: R7, S8W14, W4, G2. The mechanism of killing cancer cells was identified by lactate dehydrogenase assays and scanning electron microscopy. Mastoparan and derivatives had a direct-acting lytic mechanism that caused cell necrosis. Scanning electron microscopy showed that the membranes of Mastoparan-treated cells were substantially more damaged than those of vehicle-treated cells. Significantly more lactate dehydrogenase was released from Mastoparan-and derivative-treated cells at 25 μM than from vehicle-treated cells, indicating that the cells died by necrosis. The ability of Mastoparan and derivatives to kill three-dimensional tumours was determined using a multi-cellular tumour spheroid model and an acid phosphatase assay. Tumour spheroids were treated with 25 μM Mastoparan or derivatives and acid phosphatase activity was measured after 72 hours. Peptide treated cells had significantly decreased acid phosphatase; notably, spheroid cells treated with derivative W14 had 3.49 ± 0.35% acid phosphatase activity compared to vehicle-treated spheroids at 101.33 ± 1.11%. The present work suggests that Mastoparan and its derivatives demonstrate potential as an anti-cancer therapy for colorectal cancers.

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https://scholar.acadiau.ca/islandora/object/theses:3434