Use this url to cite publication: https://hdl.handle.net/20.500.12512/22578
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Tumoricidal HAMLET activity in colorectal cancer cell lines with different mutation status in vitro / Justas Žilinskas, Miglė Pivoriūnaitė, Mantas Šilkūnas, Giedrė Šilkūnienė, Žilvinas Dambrauskas, Antanas Gulbinas, Algimantas Tamelis
Type of publication
Recenzuojamos išplėstinės tezės / Peer-reviewed extended theses (T1d)
Author(s)
Pivoriūnaitė, Miglė | |
Title
Tumoricidal HAMLET activity in colorectal cancer cell lines with different mutation status in vitro / Justas Žilinskas, Miglė Pivoriūnaitė, Mantas Šilkūnas, Giedrė Šilkūnienė, Žilvinas Dambrauskas, Antanas Gulbinas, Algimantas Tamelis
Publisher (trusted)
Council of LSMU Doctoral Students |
Date Issued
Date Issued |
---|
2019-04-08 |
Extent
p. 72-73.
Is part of
Health for all: Science and innovation week 2019 : International doctoral and resident students conference: Science for health : abstract book : Kaunas, Lithuania, 8-12 April, 2019 / Edited by Elvinas Monstavičius, Alvita Vilkevičiūtė. Kaunas : Council of LSMU Doctoral Students, 2019.
Version
Originalus / Original
Series/Report no.
Experimental medicine.
Description
Bibliogr.: p. 73
Field of Science
Abstract
Introduction HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) is a complex of Human milk natural components α-lactalbumin and oleic acid. This protein-lipid complex has broad tumoricidal effect against cancer cells, including Colorectal cancer (CRC) [1]. Notably, the activity of HAMLET is via dysregulation of kinases and oncogenic GTPases in the epidermal growth factor receptor (EGFR)-signal pathway, causing inhibition and cancer cell death [2]. EGFR-signaling pathway is usually up-regulated in CRC while two of the many signaling molecules downstream of EGFR are RAS and RAF encoded by KRAS and BRAF genes respectfully [3,4]. Commonly, these mutations occur in CRC. Our hypothesis is that KRAS/BRAF mutation status could interact with HAMLET anticancer effectiveness. Aim To evaluate the anticancer activity of the HAMLET complex in CRC cell lines in vitro according to KRAS, BRAF mutation status. Methods HAMLET was prepared as described [5]. KRAS/BRAF mutants along with wild type cells demonstrating different mutation patterns (CaCo2, WiDr, LoVo lines [6]) was used for clinical CRC model establishment in vitro. HAMLET’s tumorocidity (metabolic activity and viability) was evaluated using 6 h. exposition and different concentration in compliance with MTT and clonogenic assays protocols. Results HAMLET complex was cytotoxic to all investigated cancer cells in dose-response manner. The dose to reduce metabolic activity (determined by MTT) as well as viability (by clonogenic assay) (IC50) in 10-15μM range in comparison to control, despite cell KRAS/BRAF mutation status. HAMLET complex components alone did not show anticancer activity. Conclusions HAMLET affects cell metabolism, this effect is severe and at the same time irreparable for cells, leading to cell death. The cytotoxicity of complex does not depend on KRAS/BRAF gene variation in CRC cell lines in vitro. HAMLET has anticancer potency for CRC treatment.
Type of document
type::text::conference output::conference proceedings::conference paper
ISSN (of the container)
2669-0314
Other Identifier(s)
(LSMU ALMA)990000980880107106
Coverage Spatial
Lietuva / Lithuania (LT)
Language
Anglų / English (en)
Bibliographic Details
6