Abuzaid, Haneen and Abdelrazig, Salah and Ferreira, Lenny and Collins, Hilary M. and Kim, Dong-Hyun and Lim, Kuan-Hon and Kam, Toh-Seok and Turyanska, Lyudmila and Bradshaw, Tracey D. (2022) Apoferritin-encapsulated jerantinine A for transferrin receptor targeting and enhanced selectivity in breast cancer therapy. ACS Omega, 7 (25). pp. 21473-21482. ISSN 2470-1343, DOI https://doi.org/10.1021/acsomega.2c00997.
Full text not available from this repository.Abstract
The O-acetyl (or acetate) derivative of the Aspidosperma alkaloid Jerantinine A (JAa) elicits anti-tumor activity against cancer cell lines including mammary carcinoma cell lines irrespective of receptor status (0.14 < GI50 < 0.38 mu M), targeting microtubule dynamics. By exploiting breast cancer cells' upregulated transferrin receptor 1 (TfR1) expression and apoferritin (AFt) recognition, we sought to develop an AFt JAa-delivery vehicle to enhance tumor-targeting and reduce systemic toxicity. Optimizing pH-mediated reassembly, similar to 120 JAa molecules were entrapped within AFt. Western blot and flow cytometry demonstrate TfR1 expression in cancer cells. Enhanced internalization of 5-carboxyfluorescein-conjugated human AFt in SKBR3 and MDA-MB-231 cancer cells is observed compared to MRC5 fibroblasts. Accordingly, AFt-JAa delivers significantly greater intracellular JAa levels to SKBR3 and MDAMB-231 cells than naked JAa (0.2 mu M) treatment alone. Compared to naked JAa (0.2 mu M), AFt-JAa achieves enhanced growth inhibition (2.5-14-fold; <0.02 mu M < GI50 < 0.15 mu M) in breast cancer cells; AFt-JAa treatment results in significantly reduced clonal survival, more profound cell cycle perturbation including G2/M arrest, greater reduction in cell numbers, and increased apoptosis compared to the naked agent (p < 0.01). Decreased PLK1 and Mcl-1 expression, together with the appearance of cleaved poly (ADP-ribose)polymerase, corroborate the augmented potency of AFt-JAa. Hence, we demonstrate that AFt represents a biocompatible vehicle for targeted delivery of JAa, offering potential to minimize toxicity and enhance JAa activity in TfR1-expressing tumors.
| Item Type: | Article |
|---|---|
| Funders: | UK Research & Innovation (UKRI), Engineering & Physical Sciences Research Council (EPSRC) NC/L001861/1, National Centre for the Replacement, Refinement & Reduction of Animals in Research (NC3Rs), UK Research & Innovation (UKRI), Engineering & Physical Sciences Research Council (EPSRC) EP/K503800/1, Al-Zaytoonah University of Jordan |
| Uncontrolled Keywords: | Ferritin; Cells; Chemotherapy; Expression; Apoptosis; Binding |
| Subjects: | R Medicine > RC Internal medicine |
| Divisions: | Faculty of Science > Department of Chemistry |
| Depositing User: | Ms. Juhaida Abd Rahim |
| Date Deposited: | 19 Oct 2023 02:24 |
| Last Modified: | 23 Oct 2023 08:55 |
| URI: | http://eprints.um.edu.my/id/eprint/41924 |
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