| Autor: |
Bimala Dhakal, Celine Man Ying Li, Runhao Li, Kenny Yeo, Josephine A. Wright, Krystyna A. Gieniec, Laura Vrbanac, Tarik Sammour, Matthew Lawrence, Michelle Thomas, Mark Lewis, Joanne Perry, Daniel L. Worthley, Susan L. Woods, Paul Drew, Benedetta C. Sallustio, Eric Smith, John D. Horowitz, Guy J. Maddern, Giovanni Licari, Kevin Fenix |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Cancers, Vol 14, Iss 4, p 1043 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2072-6694 |
| DOI: |
10.3390/cancers14041043 |
| Popis: |
Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide. Perhexiline, a prophylactic anti-anginal drug, has been reported to have anti-tumour effects both in vitro and in vivo. Perhexiline as used clinically is a 50:50 racemic mixture ((R)-P) of (−) and (+) enantiomers. It is not known if the enantiomers differ in terms of their effects on cancer. In this study, we examined the cytotoxic capacity of perhexiline and its enantiomers ((−)-P and (+)-P) on CRC cell lines, grown as monolayers or spheroids, and patient-derived organoids. Treatment of CRC cell lines with (R)-P, (−)-P or (+)-P reduced cell viability, with IC50 values of ~4 µM. Treatment was associated with an increase in annexin V staining and caspase 3/7 activation, indicating apoptosis induction. Caspase 3/7 activation and loss of structural integrity were also observed in CRC cell lines grown as spheroids. Drug treatment at clinically relevant concentrations significantly reduced the viability of patient-derived CRC organoids. Given these in vitro findings, perhexiline, as a racemic mixture or its enantiomers, warrants further investigation as a repurposed drug for use in the management of CRC. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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