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Pelophen B is a non-taxoid binding microtubule-stabilizing agent with promising preclinical anticancer properties

Stephanie Vermeulen (UGent) , Sam Ernst (UGent) , Eva Blondeel (UGent) , Zihan Xia (UGent) , Pekka Rappu, Jyrki Heino, Sandor Dedeyne (UGent) , Hannelore Denys (UGent) , Gwen Sys (UGent) , Stefanie Gijsels (UGent) , et al.
(2024) SCIENTIFIC REPORTS. 14(1).
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Abstract
Taxanes, such as paclitaxel (PTX), stabilize microtubules and are used as a first-line therapy in multiple cancer types. Disruption of microtubule equilibrium, which plays an essential role in mitosis and cell homeostasis, ultimately results in cell death. Even though PTX is a very potent chemotherapy, its use is associated with major side effects and therapy resistance. Pelophen B (PPH), a synthetic analog of peloruside A, stabilizes microtubules through interaction with a non-taxoid binding site of β-tubulin. We evaluated the anticancer effect of PPH in a variety of tumor types by using established cell lines, early-passage cultures and ex vivo tumor-derived cultures that preserve the 3D architecture of the tumor microenvironment. PPH significantly blocks colony formation capacity, reduces viability and exerts additivity with PTX. Interestingly, PPH overcomes resistance to PTX. Mechanistically, PPH induces a G2/M cell cycle arrest and increases the presence of tubulin polymerization promoting protein (TPPP), inducing lysine 40 acetylation of α-tubulin. Although, results induced by paclitaxel or PPH are concordant, PPH’s unique microtubule binding mechanism enables PTX additivity and ensures overcoming PTX-induced resistance. In conclusion, PPH results in remarkable anti-cancer activity in a range of preclinical models supporting further clinical investigation of PPH as a therapeutic anticancer agent.
Keywords
Breast cancer, Ovarian cancer, Sarcoma, Pelophen B, Paclitaxel, Microtubule-stabilizing agent, PELORUSIDE-A, TUBULIN ACETYLATION, BETA-TUBULIN, CELL-DEATH, MECHANISMS, SENSITIVITY, DISEASE, TAXANE, GROWTH, SITE

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MLA
Vermeulen, Stephanie, et al. “Pelophen B Is a Non-Taxoid Binding Microtubule-Stabilizing Agent with Promising Preclinical Anticancer Properties.” SCIENTIFIC REPORTS, vol. 14, no. 1, 2024, doi:10.1038/s41598-024-80672-z.
APA
Vermeulen, S., Ernst, S., Blondeel, E., Xia, Z., Rappu, P., Heino, J., … De Wever, O. (2024). Pelophen B is a non-taxoid binding microtubule-stabilizing agent with promising preclinical anticancer properties. SCIENTIFIC REPORTS, 14(1). https://doi.org/10.1038/s41598-024-80672-z
Chicago author-date
Vermeulen, Stephanie, Sam Ernst, Eva Blondeel, Zihan Xia, Pekka Rappu, Jyrki Heino, Sandor Dedeyne, et al. 2024. “Pelophen B Is a Non-Taxoid Binding Microtubule-Stabilizing Agent with Promising Preclinical Anticancer Properties.” SCIENTIFIC REPORTS 14 (1). https://doi.org/10.1038/s41598-024-80672-z.
Chicago author-date (all authors)
Vermeulen, Stephanie, Sam Ernst, Eva Blondeel, Zihan Xia, Pekka Rappu, Jyrki Heino, Sandor Dedeyne, Hannelore Denys, Gwen Sys, Stefanie Gijsels, Herman Depypere, Philippe Tummers, Wim Ceelen, Ligia Craciun, Pieter Demetter, Olivier Raes, An Hendrix, Johan Van der Eycken, and Olivier De Wever. 2024. “Pelophen B Is a Non-Taxoid Binding Microtubule-Stabilizing Agent with Promising Preclinical Anticancer Properties.” SCIENTIFIC REPORTS 14 (1). doi:10.1038/s41598-024-80672-z.
Vancouver
1.
Vermeulen S, Ernst S, Blondeel E, Xia Z, Rappu P, Heino J, et al. Pelophen B is a non-taxoid binding microtubule-stabilizing agent with promising preclinical anticancer properties. SCIENTIFIC REPORTS. 2024;14(1).
IEEE
[1]
S. Vermeulen et al., “Pelophen B is a non-taxoid binding microtubule-stabilizing agent with promising preclinical anticancer properties,” SCIENTIFIC REPORTS, vol. 14, no. 1, 2024.
@article{01JEBJ6FTBJM9FXP5G71BQQQ7M,
  abstract     = {{Taxanes, such as paclitaxel (PTX), stabilize microtubules and are used as a first-line therapy in multiple cancer types. Disruption of microtubule equilibrium, which plays an essential role in mitosis and cell homeostasis, ultimately results in cell death. Even though PTX is a very potent chemotherapy, its use is associated with major side effects and therapy resistance. Pelophen B (PPH), a synthetic analog of peloruside A, stabilizes microtubules through interaction with a non-taxoid binding site of β-tubulin. We evaluated the anticancer effect of PPH in a variety of tumor types by using established cell lines, early-passage cultures and ex vivo tumor-derived cultures that preserve the 3D architecture of the tumor microenvironment. PPH significantly blocks colony formation capacity, reduces viability and exerts additivity with PTX. Interestingly, PPH overcomes resistance to PTX. Mechanistically, PPH induces a G2/M cell cycle arrest and increases the presence of tubulin polymerization promoting protein (TPPP), inducing lysine 40 acetylation of α-tubulin. Although, results induced by paclitaxel or PPH are concordant, PPH’s unique microtubule binding mechanism enables PTX additivity and ensures overcoming PTX-induced resistance. In conclusion, PPH results in remarkable anti-cancer activity in a range of preclinical models supporting further clinical investigation of PPH as a therapeutic anticancer agent.}},
  articleno    = {{30188}},
  author       = {{Vermeulen, Stephanie and Ernst, Sam and Blondeel, Eva and Xia, Zihan and Rappu, Pekka and Heino, Jyrki and Dedeyne, Sandor and Denys, Hannelore and Sys, Gwen and Gijsels, Stefanie and Depypere, Herman and Tummers, Philippe and Ceelen, Wim and Craciun, Ligia and Demetter, Pieter and Raes, Olivier and Hendrix, An and Van der Eycken, Johan and De Wever, Olivier}},
  issn         = {{2045-2322}},
  journal      = {{SCIENTIFIC REPORTS}},
  keywords     = {{Breast cancer,Ovarian cancer,Sarcoma,Pelophen B,Paclitaxel,Microtubule-stabilizing agent,PELORUSIDE-A,TUBULIN ACETYLATION,BETA-TUBULIN,CELL-DEATH,MECHANISMS,SENSITIVITY,DISEASE,TAXANE,GROWTH,SITE}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{13}},
  title        = {{Pelophen B is a non-taxoid binding microtubule-stabilizing agent with promising preclinical anticancer properties}},
  url          = {{http://doi.org/10.1038/s41598-024-80672-z}},
  volume       = {{14}},
  year         = {{2024}},
}
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