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

Background: Arbutus pavarii Pamp. (fam. Ericaceae), commonly known as “Shmeri”, “Shmar” and “Libyan Strawberry”, is an endemic Libyan medicinal plant, growing almost exclusively in the Al-Jabel Al-Akhdar mountainous region in Libya. Aims: To assess the cytotoxicity of A. pavarii 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. 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 was more cytotoxic against the PC3 cell line (IC50= 26 mg/mL) but less to the normal human prostate cell line PNT2 (IC50 = 90 mg/mL) with a selectivity index of 3.5. VLC analysis produced 8 fractions, with fraction VLC-5 most active against PC3 cells. 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

Arbutin: Occurrence in Plants, and Its Potential as an Anticancer Agent

Arbutin, a hydroquinone glucoside, has been detected in ca. 50 plant families, especially in the plants of the Asteraceae, Ericaceae, Proteaceae and Rosaceae families. It is one of the most widely used natural skin-whitening agents. In addition to its skin whitening property, arbutin possesses other therapeutically relevant biological properties, e.g., antioxidant, antimicrobial and anti-inflammatory, as well as anticancer potential. This review presents, for the first time, a comprehensive overview of the distribution of arbutin in the plant kingdom and critically appraises its therapeutic potential as an anticancer agent based on the literature published until the end of August 2022, accessed via several databases, e.g., Web of Science, Science Direct, Dictionary of Natural Products, PubMed and Google Scholar. The keywords used in the search were arbutin, cancer, anticancer, distribution and hydroquinone. Published outputs suggest that arbutin has potential anticancer properties against bladder, bone, brain, breast, cervix, colon, liver, prostate and skin cancers and a low level of acute or chronic toxicity

Chalepin and Chalepensin: Occurrence, Biosynthesis and Therapeutic Potential

Dihydrofuranocoumarin, chalepin (1) and furanocoumarin, chalepensin (2) are 3-prenylated bioactive coumarins, first isolated from the well-known medicinal plant Ruta chalepensis L. (Fam: Rutaceae) but also distributed in various species of the genera Boenminghausenia, Clausena and Ruta. The distribution of these compounds appears to be restricted to the plants of the family Rutaceae. To date, there have been a considerable number of bioactivity studies performed on coumarins 1 and 2, which include their anticancer, antidiabetic, antifertility, antimicrobial, antiplatelet aggregation, antiprotozoal, antiviral and calcium antagonistic properties. This review article presents a critical appraisal of publications on bioactivity of these 3-prenylated coumarins in the light of their feasibility as novel therapeutic agents and investigate their natural distribution in the plant kingdom, as well as a plausible biosynthetic route

Cytotoxicity of Libyan Juniperus phoenicea against Human Cancer Cell Lines A549, EJ138, Hepg2 and MCF7

Background: The current study was undertaken to assess the cytotoxicity of the leaves of Libyan Juniperus phoenicea (Cupressaceae) against human cancer cell lines. Methods: The cytotoxicity of the n-hexane, dichloromethane (DCM) and methanol (MeOH) extracts of the leaves of J. phoenicea (JP), obtained from sequential Soxhlet extractions, was assessed against four human cancer cell lines: EJ138 (human bladder carcinoma), HepG2 (human liver hepatocellular carcinoma), A549 (human lung carcinoma) and MCF7 (human breast adenocarcinoma) using the MTT assay. Results: The cell line A549 was the most sensitive to the JP extracts, with the highest level of cytotoxicity with the IC50 values of 16, 13 and 100 µg/mL for the DCM, n-hexane and MeOH extracts, respectively. However, generally the most potent cytotoxic extract across the other cells tested was the n-hexane extract, followed by the DCM extract, whilst the MeOH extracts showed little or no cytotoxicity. The percentage of viability of cells decreased as the concentration of test compounds increased. The cytotoxicity of various chromatographic fractions from the extracts was also studied against the A459 cells. For the n-hexane fractions, the IC50 values were 160, 62, 90, 30, 9.5 and 40 µg/mL for fractions 1 to 5 and 7, respectively. Fractions 4 and 5 showed the greatest effect. DCM fractions 2, 3 and 4 had the IC50 values of 60, 92 and 19 µg/mL, respectively, and DCM fractions 5 to 8 were non-cytotoxic. Fractions 1 and 2 of the MeOH extract were non-cytotoxic, whereas cytotoxicity was observed for fractions 3 and 4 with IC50 values of 50 and 85 µg/mL, respectively. Conclusion: The outcome of the present study suggested that the JP leaves possess cytotoxic activities. The high level of cytotoxicity of the n-hexane and DCM extracts suggested that lipophilicity might affect the cytotoxicity of JP, where the less polar compounds had the strongest cytotoxicity