Dysobinol from  Chisocheton macrophyllus  Selectively Induces G1 Cell Cycle Arrest in MCF-7 Breast Cancer Cells

Shabarni Gaffar; Ghina Uli Felicia Tambunan; Ersanda Hafiz; Tati Herlina; Hesti Lina Wiraswati; Nurlelasari Nurlelasari; Ilma Fauziah Ma'ruf

doi:10.22146/ijc.100479

Dysobinol from Chisocheton macrophyllus Selectively Induces G1 Cell Cycle Arrest in MCF-7 Breast Cancer Cells

https://doi.org/10.22146/ijc.100479

Shabarni Gaffar^(1*), Ghina Uli Felicia Tambunan⁽²⁾, Ersanda Hafiz⁽³⁾, Tati Herlina⁽⁴⁾, Hesti Lina Wiraswati⁽⁵⁾, Nurlelasari Nurlelasari⁽⁶⁾, Ilma Fauziah Ma'ruf⁽⁷⁾

(1) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(2) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(3) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(4) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(5) Department of Biomedical Sciences, Faculty of Medicine, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(6) Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Jl. Raya Bandung-Sumedang Km. 21, Jatinangor, Sumedang 45363, Indonesia
(7) Research Center for Climate and Atmosphere, National Research and Innovation Agency, Jl. Sangkuriang, Bandung 40135, Indonesia
(*) Corresponding Author

Abstract

Chisocheton macrophyllus is a medicinal plant that contains sesquiterpenoids, triterpenoids, limonoids, steroids, and phenolic compounds. This research aimed to assess the effect of Dysobinol, a limonoid compound from the seed of C. macrophyllus, on MCF-7 cell growth. Cell viability was evaluated using the MTS colorimetric assay, DNA fragmentation was assessed by agarose electrophoresis, apoptosis and cell cycle arrest were determined by flow cytometry, and gene expression levels were evaluated using qRT-PCR. Dysobinol was also analyzed in silico using drug-likeness, pharmacokinetic, and molecular docking analysis. Dysobinol demonstrated moderate cytotoxicity against MCF-7 cells, with an IC₅₀ of 148.20 μg/mL. Dysobinol induced G1 phase cell cycle arrest that was not accompanied by the induction of apoptosis in MCF-7 cells. In silico studies showed that the EGFR/AKT/cyclin D1 proteins were affected by Dysobinol. Furthermore, drug-likeness and pharmacokinetics analysis showed that Dysobinol is bioavailable orally and has high gastrointestinal absorption and low penetration into the blood-brain barrier. Together, these results indicate that Dysobinol can regulate breast cancer cell proliferation through cell cycle arrest rather than apoptosis, and its pharmacological profile highlights its potential as a promising lead compound for anticancer drug development.

Keywords

cell cycle arrest; Dysobinol; DNA fragmentation; molecular docking; pharmacokinetics

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DOI: https://doi.org/10.22146/ijc.100479