Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy

Selda Abyar; Luojiao Huang; Yurii Husiev; Ludovic Bretin; Bobby Chau; Vadde Ramu; Jacob Hendricus Wildeman; Kimberley Belfor; Lukas S. Wijaya; Vera E. van der Noord; Amy C. Harms; Maxime A. Siegler; Sylvia E. le Dévédec; Sylvestre Bonnet

doi:10.1021/acs.jmedchem.4c00589

Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy

Selda Abyar
, Luojiao Huang
, Yurii Husiev
, Ludovic Bretin
, Bobby Chau
, Vadde Ramu
, Jacob Hendricus Wildeman
, Kimberley Belfor
, Lukas S. Wijaya
, Vera E. van der Noord
, Amy C. Harms
, Maxime A. Siegler
, Sylvia E. le Dévédec^*
, Sylvestre Bonnet^*

^*Corresponding author for this work

Affiliatie VU

Leiden University
Johns Hopkins University

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound Ru-STF31 in the glioblastoma cancer cell line, U87MG. Ru-STF31 targets nicotinamide phosphoribosyltransferase (NAMPT), an enzyme overexpressed in U87MG. Ru-STF31 is activated by red light irradiation and releases two photoproducts: the ruthenium cage and the cytotoxic inhibitor STF31. This study shows that Ru-STF31 can significantly decrease intracellular NAD+ levels in both normoxic (21% O2) and hypoxic (1% O2) U87MG cells. Strikingly, NAD+ depletion by light activation of Ru-STF31 in hypoxic U87MG cells could not be rescued by the addition of extracellular NAD+. Our data suggest an oxygen-dependent active role of the ruthenium photocage released by light activation.

Original language	English
Pages (from-to)	11086-11102
Number of pages	17
Journal	Journal of medicinal chemistry
Volume	67
Issue number	13
DOIs	https://doi.org/10.1021/acs.jmedchem.4c00589
Publication status	Published - 11 Jul 2024

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Oxygen-dependent-interactions-between-the-ruthenium-cage-and-the-photoreleased-inhibitor-in-nampt-targeted-photoactivate.pdfFinal published version, 5.17 MBLicence: CC BY

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Abyar, S., Huang, L., Husiev, Y., Bretin, L., Chau, B., Ramu, V., Wildeman, J. H., Belfor, K., Wijaya, L. S., van der Noord, V. E., Harms, A. C., Siegler, M. A., le Dévédec, S. E., & Bonnet, S. (2024). Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy. Journal of medicinal chemistry, 67(13), 11086-11102. https://doi.org/10.1021/acs.jmedchem.4c00589

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title = "Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy",

abstract = "Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound Ru-STF31 in the glioblastoma cancer cell line, U87MG. Ru-STF31 targets nicotinamide phosphoribosyltransferase (NAMPT), an enzyme overexpressed in U87MG. Ru-STF31 is activated by red light irradiation and releases two photoproducts: the ruthenium cage and the cytotoxic inhibitor STF31. This study shows that Ru-STF31 can significantly decrease intracellular NAD+ levels in both normoxic (21\% O2) and hypoxic (1\% O2) U87MG cells. Strikingly, NAD+ depletion by light activation of Ru-STF31 in hypoxic U87MG cells could not be rescued by the addition of extracellular NAD+. Our data suggest an oxygen-dependent active role of the ruthenium photocage released by light activation.",

author = "Selda Abyar and Luojiao Huang and Yurii Husiev and Ludovic Bretin and Bobby Chau and Vadde Ramu and Wildeman, \{Jacob Hendricus\} and Kimberley Belfor and Wijaya, \{Lukas S.\} and \{van der Noord\}, \{Vera E.\} and Harms, \{Amy C.\} and Siegler, \{Maxime A.\} and \{le D{\'e}v{\'e}dec\}, \{Sylvia E.\} and Sylvestre Bonnet",

note = "Publisher Copyright: {\textcopyright} 2024 The Authors. Published by American Chemical Society.",

year = "2024",

month = jul,

day = "11",

doi = "10.1021/acs.jmedchem.4c00589",

language = "English",

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Abyar, S, Huang, L, Husiev, Y, Bretin, L, Chau, B, Ramu, V, Wildeman, JH, Belfor, K, Wijaya, LS, van der Noord, VE, Harms, AC, Siegler, MA, le Dévédec, SE & Bonnet, S 2024, 'Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy', Journal of medicinal chemistry, vol. 67, no. 13, pp. 11086-11102. https://doi.org/10.1021/acs.jmedchem.4c00589

TY - JOUR

T1 - Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy

AU - Abyar, Selda

AU - Huang, Luojiao

AU - Husiev, Yurii

AU - Bretin, Ludovic

AU - Chau, Bobby

AU - Ramu, Vadde

AU - Wildeman, Jacob Hendricus

AU - Belfor, Kimberley

AU - Wijaya, Lukas S.

AU - van der Noord, Vera E.

AU - Harms, Amy C.

AU - Siegler, Maxime A.

AU - le Dévédec, Sylvia E.

AU - Bonnet, Sylvestre

PY - 2024/7/11

Y1 - 2024/7/11

N2 - Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound Ru-STF31 in the glioblastoma cancer cell line, U87MG. Ru-STF31 targets nicotinamide phosphoribosyltransferase (NAMPT), an enzyme overexpressed in U87MG. Ru-STF31 is activated by red light irradiation and releases two photoproducts: the ruthenium cage and the cytotoxic inhibitor STF31. This study shows that Ru-STF31 can significantly decrease intracellular NAD+ levels in both normoxic (21% O2) and hypoxic (1% O2) U87MG cells. Strikingly, NAD+ depletion by light activation of Ru-STF31 in hypoxic U87MG cells could not be rescued by the addition of extracellular NAD+. Our data suggest an oxygen-dependent active role of the ruthenium photocage released by light activation.

AB - Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound Ru-STF31 in the glioblastoma cancer cell line, U87MG. Ru-STF31 targets nicotinamide phosphoribosyltransferase (NAMPT), an enzyme overexpressed in U87MG. Ru-STF31 is activated by red light irradiation and releases two photoproducts: the ruthenium cage and the cytotoxic inhibitor STF31. This study shows that Ru-STF31 can significantly decrease intracellular NAD+ levels in both normoxic (21% O2) and hypoxic (1% O2) U87MG cells. Strikingly, NAD+ depletion by light activation of Ru-STF31 in hypoxic U87MG cells could not be rescued by the addition of extracellular NAD+. Our data suggest an oxygen-dependent active role of the ruthenium photocage released by light activation.

UR - https://www.scopus.com/pages/publications/85196967274

U2 - 10.1021/acs.jmedchem.4c00589

DO - 10.1021/acs.jmedchem.4c00589

M3 - Article

C2 - 38924492

SN - 0022-2623

VL - 67

SP - 11086

EP - 11102

JO - Journal of medicinal chemistry

JF - Journal of medicinal chemistry

IS - 13

ER -

Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy

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