Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

Sotiris Kyriakou; Melina Mitsiogianni; Theodora Mantso; William Cheung; Stephen Todryk; Stephany Veuger; Aglaia Pappa; David Tetard; Mihalis Panagiotidis

doi:10.1007/s10637-019-00809-0

Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

Sotiris Kyriakou, Melina Mitsiogianni, Theodora Mantso, William Cheung, Stephen Todryk, Stephany Veuger, Aglaia Pappa, David Tetard, Mihalis Panagiotidis

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Abstract

The anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of L-mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the L-enantiomer of a methylated analogue of L-mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.

Original language	English
Pages (from-to)	621-633
Number of pages	13
Journal	Investigational New Drugs
Volume	38
Issue number	3
Early online date	26 Jun 2019
DOIs	https://doi.org/10.1007/s10637-019-00809-0
Publication status	Published - 1 Jun 2020

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Anticancer activity
L-mimosine analogues
Melanoma
Metal chelators
Skin cancer

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Kyriakou et alAccepted author manuscript, 858 KB
Kyriakou2020_Article_AnticancerActivityOfANovelMethFinal published version, 2.1 MBLicence: CC BY
Kyriakou2019_Article_AnticancerActivityOfANovelMethFinal published version, 2.09 MBLicence: CC BY

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title = "Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma",

abstract = "The anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of L-mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the L-enantiomer of a methylated analogue of L-mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.",

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AU - Kyriakou, Sotiris

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AU - Cheung, William

AU - Todryk, Stephen

AU - Veuger, Stephany

AU - Pappa, Aglaia

AU - Tetard, David

AU - Panagiotidis, Mihalis

N1 - Funding Information: Funding This work was supported by start-up funds (MIP) including PhD studentships (SK & MM) provided by the Multi-Disciplinary Research Theme in “Bio-economy” of Northumbria University. Publisher Copyright: © 2019, The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/6/1

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N2 - The anticancer activity of a series of novel synthesized, hydroxypyridone-based metal chelators (analogues of L-mimosine) was evaluated in an in vitro model of melanoma consisting of malignant melanoma (A375), non-melanoma epidermoid carcinoma (A431) and immortalized non-malignant keratinocyte (HaCaT) cells. More specifically, we have demonstrated that the L-enantiomer of a methylated analogue of L-mimosine (compound 22) can exert a potent anticancer effect in A375 cells when compared to either A431 or HaCaT cells. Moreover, we have demonstrated that this analogue has the ability to i) promote increased generation of reactive oxygen species (ROS), ii) activate both intrinsic and extrinsic apoptosis and iii) induce perturbations in cell cycle growth arrest. Our data highlights the potential of compound 22 to act as a promising therapeutic agent against an in vitro model of human malignant melanoma.

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Anticancer activity of a novel methylated analogue of L-mimosine against an in vitro model of human malignant melanoma

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