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Dichloromethane Extract of the Leaves of Arbutus pavarii Pamp. Exhibits Cytotoxicity Against the Prostate Cancer Cell Line PC3: A Bioassay-guided Isolation and Identification of Arbutin and Betulinic Acid Methyl Ester

Al Groshi, A, Nahar, L, Ismail, FMD, Evans, AR and Sarker, SD Dichloromethane Extract of the Leaves of Arbutus pavarii Pamp. Exhibits Cytotoxicity Against the Prostate Cancer Cell Line PC3: A Bioassay-guided Isolation and Identification of Arbutin and Betulinic Acid Methyl Ester. Turkish Journal of Pharmaceutical Sciences. ISSN 1304-530X (Accepted)

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Abstract

Objectives: To assess the cytotoxicity of Arbutus pavarii Pamp. (fam. Ericaceae), a Libyan medicinal plant, against human cancer cell lines and to carry out bioassay-guided isolation and identification of compounds.
Materials and Methods: Shed-dried and ground leaves of A. pavarii were Soxhlet-extracted, successively, with n-hexane, dichloromethane (DCM) and methanol (MeOH), and assessed for cytotoxicity against several human cancer cell lines using the MTT assay. The cytotoxicity of the DCM extract against the normal human prostate cell line PNT2 was also assessed to determine the selectivity index (SI). The DCM extract was subjected to vacuum liquid chromatography (VLC) to produce eight fractions, which were then tested against the prostate cancer cell line PC3, as the DCM extract was considerably cytotoxic to this cell line. A reversed-phase preparative HPLC analysis of the active VLC fraction was carried out to purify the major compounds present in the active fraction, and the structures of the compounds were elucidated by spectroscopic means.
Results: The DCM extract displayed most prominent cytotoxicity against the PC3 cell line with an IC50 value of 26 g/mL. However, this extract was much less cytotoxic to the normal human prostate cell line PNT2 (IC50 = 90 g/mL) with a selectivity index of 3.5. VLC analysis produced eight fractions, and among them, fraction VLC-5 was most active against the PC3 cell line. Prep-HPLC-based purification of VLC-5 afforded the isolation of arbutin (1) and betulinic acid methyl ester (2), the structures of which were elucidated by spectroscopic means.
Conclusion: The DCM extract of the leaves of A. pavarii exhibited significant cytotoxicity to PC3 cells, but much less cytotoxicity against normal human prostate cell line. The isolated compounds from the active fraction, arbutin (1) and betulinic acid methyl ester (2), which were previously shown to possess cytotoxic properties, could be responsible for the cytotoxicity of the DCM extract.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
R Medicine > RV Botanic, Thomsonian, and eclectic medicine
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Galenos Yayinevi
Date Deposited: 28 Sep 2021 09:27
Last Modified: 28 Sep 2021 09:30
URI: https://researchonline.ljmu.ac.uk/id/eprint/15566

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