Tetracenomycin Aglycones Primarily Inhibit Cell Growth and Proliferation in Mammalian Cancer Cell Lines

Kyah Birdsall; Adwowa B.S. Brako; Courtney Brown; Kendall Paige; Alexis West; Nora Schwartz; Jacob Hecht; Katelyn V. Brown; Jon S. Thorson; Khaled A. Shaaban; S. Eric Nybo

doi:10.3390/app152211985

Tetracenomycin Aglycones Primarily Inhibit Cell Growth and Proliferation in Mammalian Cancer Cell Lines

Kyah Birdsall, Adwowa B.S. Brako, Courtney Brown, Kendall Paige, Alexis West, Nora Schwartz, Jacob Hecht, Katelyn V. Brown, Jon S. Thorson, Khaled A. Shaaban, S. Eric Nybo

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

Abstract

Tetracenomycins are anticancer polyketides that arrest cancer cell proliferation via binding to the large mammalian ribosomal subunit near the polypeptide exit channel. The tetracenomycins are natural products that many members of the actinomycete family produce. The first goal of this study was to improve the biosynthesis of tetracenomycin analogs via metabolic engineering. The second goal was to probe more deeply into the antiproliferative activity of tetracenomycin aglycones. The tetracenomycins were assessed via several assays, including cell viability assays, clonogenic assays, and flow cytometry apoptosis assays. The data suggest that tetracenomycins C and X inhibit cell proliferation and arrest cell growth, supporting their cytostatic action mechanism. In addition, tetracenomycins C and X induced degeneration of 3D spheroid cultures and exhibited concentration-dependent inhibition of cell survival and colony formation in clonogenic assays. This work demonstrates that tetracenomycins act mainly as cytostatic rather than apoptotic agents.

Original language	English
Article number	11985
Journal	Applied Sciences (Switzerland)
Volume	15
Issue number	22
DOIs	https://doi.org/10.3390/app152211985
State	Published - Nov 2025

Bibliographical note

Publisher Copyright:
© 2025 by the authors.

Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award No. R15CA252830 (to S.E.N.) and the National Science Foundation under Grant No. ENG-2015951 (to S.E.N.). This work was also supported by National Institutes of Health grant R37 AI052218 (J.S.T.), the Center of Biomedical Research Excellence (COBRE) for Translational Chemical Biology (CTCB, NIH P20 GM130456), the National Institute of Food and Agriculture (USDA-NIFA-CBGP, Grant No. 2023-38821-39584; K.A.S. and J.S.T), the University of Kentucky College of Pharmacy, the University of Kentucky Markey Cancer Center and the National Center for Advancing Translational Sciences (UL1TR000117 and UL1TR001998).

Funders	Funder number
University of Kentucky
University of Kentucky Markey Comprehensive Cancer Center
Center of Biomedical Research Excellence
National Childhood Cancer Registry – National Cancer Institute
National Institutes of Health (NIH)	P20 GM130456, R15CA252830
US Department of Agriculture National Institute of Food and Agriculture, Agriculture and Food Research Initiative	2023-38821-39584
National Science Foundation Arctic Social Science Program	R37 AI052218, ENG-2015951
National Center for Advancing Translational Sciences (NCATS)	UL1TR001998, UL1TR000117

Keywords

aglycone
anticancer
cell viability
spheroid
tetracenomycins

ASJC Scopus subject areas

General Materials Science
Instrumentation
General Engineering
Process Chemistry and Technology
Computer Science Applications
Fluid Flow and Transfer Processes

UN SDGs

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

Access to Document

10.3390/app152211985

Cite this

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title = "Tetracenomycin Aglycones Primarily Inhibit Cell Growth and Proliferation in Mammalian Cancer Cell Lines",

abstract = "Tetracenomycins are anticancer polyketides that arrest cancer cell proliferation via binding to the large mammalian ribosomal subunit near the polypeptide exit channel. The tetracenomycins are natural products that many members of the actinomycete family produce. The first goal of this study was to improve the biosynthesis of tetracenomycin analogs via metabolic engineering. The second goal was to probe more deeply into the antiproliferative activity of tetracenomycin aglycones. The tetracenomycins were assessed via several assays, including cell viability assays, clonogenic assays, and flow cytometry apoptosis assays. The data suggest that tetracenomycins C and X inhibit cell proliferation and arrest cell growth, supporting their cytostatic action mechanism. In addition, tetracenomycins C and X induced degeneration of 3D spheroid cultures and exhibited concentration-dependent inhibition of cell survival and colony formation in clonogenic assays. This work demonstrates that tetracenomycins act mainly as cytostatic rather than apoptotic agents.",

keywords = "aglycone, anticancer, cell viability, spheroid, tetracenomycins",

author = "Kyah Birdsall and Brako, \{Adwowa B.S.\} and Courtney Brown and Kendall Paige and Alexis West and Nora Schwartz and Jacob Hecht and Brown, \{Katelyn V.\} and Thorson, \{Jon S.\} and Shaaban, \{Khaled A.\} and Nybo, \{S. Eric\}",

note = "Publisher Copyright: {\textcopyright} 2025 by the authors.",

year = "2025",

month = nov,

doi = "10.3390/app152211985",

language = "English",

volume = "15",

number = "22",

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T1 - Tetracenomycin Aglycones Primarily Inhibit Cell Growth and Proliferation in Mammalian Cancer Cell Lines

AU - Birdsall, Kyah

AU - Brako, Adwowa B.S.

AU - Brown, Courtney

AU - Paige, Kendall

AU - West, Alexis

AU - Schwartz, Nora

AU - Hecht, Jacob

AU - Brown, Katelyn V.

AU - Thorson, Jon S.

AU - Shaaban, Khaled A.

AU - Nybo, S. Eric

PY - 2025/11

Y1 - 2025/11

N2 - Tetracenomycins are anticancer polyketides that arrest cancer cell proliferation via binding to the large mammalian ribosomal subunit near the polypeptide exit channel. The tetracenomycins are natural products that many members of the actinomycete family produce. The first goal of this study was to improve the biosynthesis of tetracenomycin analogs via metabolic engineering. The second goal was to probe more deeply into the antiproliferative activity of tetracenomycin aglycones. The tetracenomycins were assessed via several assays, including cell viability assays, clonogenic assays, and flow cytometry apoptosis assays. The data suggest that tetracenomycins C and X inhibit cell proliferation and arrest cell growth, supporting their cytostatic action mechanism. In addition, tetracenomycins C and X induced degeneration of 3D spheroid cultures and exhibited concentration-dependent inhibition of cell survival and colony formation in clonogenic assays. This work demonstrates that tetracenomycins act mainly as cytostatic rather than apoptotic agents.

AB - Tetracenomycins are anticancer polyketides that arrest cancer cell proliferation via binding to the large mammalian ribosomal subunit near the polypeptide exit channel. The tetracenomycins are natural products that many members of the actinomycete family produce. The first goal of this study was to improve the biosynthesis of tetracenomycin analogs via metabolic engineering. The second goal was to probe more deeply into the antiproliferative activity of tetracenomycin aglycones. The tetracenomycins were assessed via several assays, including cell viability assays, clonogenic assays, and flow cytometry apoptosis assays. The data suggest that tetracenomycins C and X inhibit cell proliferation and arrest cell growth, supporting their cytostatic action mechanism. In addition, tetracenomycins C and X induced degeneration of 3D spheroid cultures and exhibited concentration-dependent inhibition of cell survival and colony formation in clonogenic assays. This work demonstrates that tetracenomycins act mainly as cytostatic rather than apoptotic agents.

KW - aglycone

KW - anticancer

KW - cell viability

KW - spheroid

KW - tetracenomycins

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U2 - 10.3390/app152211985

DO - 10.3390/app152211985

M3 - Article

AN - SCOPUS:105023114268

VL - 15

JO - Applied Sciences (Switzerland)

JF - Applied Sciences (Switzerland)

IS - 22

M1 - 11985

ER -

Tetracenomycin Aglycones Primarily Inhibit Cell Growth and Proliferation in Mammalian Cancer Cell Lines

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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