This thesis examined the in vitrophytochemical and cytotoxicity/anticancer activities of four selected plants from the Libyan flora. Based on information on traditional medicinal uses and a literature survey, Bougainvillea spectabilis Willd. (Fam: Nyctaginaceae), Alhagi graecorum Boiss (Fam: Fabaceae) Retama raetam (Forssk.) Webb & Berthel. (Fam: Fabaceae), and Psoralea plicata (Fam: Fabaceae) were selected. The four plants were investigated phytochemically and a range of compounds were elucidated, including: pinitol, allantoin, trigonelline, narcissin, alpinumisoflavone, 8-β-D-glucopyranosylgenistein, ephedroidin, plicatin-A, psoralen, angelicin and daidzein. The study concentrated on the evaluation of n-hexane, ethylacetate (EtOAc),methanol (MeOH) and ethanol (EtOH) solvent plant extracts and some of the isolated compounds for cytotoxicity based on metabolic activity to evaluate the potential anticancer activity against six human tumour cell lines: human Caucasian hepatocyte carcinoma (HepG2), human malignant melanoma (A375), human Caucasian lung carcinoma (A549), human Caucas ian pancreas carcinoma (PANC-1), human Caucasian breast adenocarcinoma (MCF7), human Caucasian prostate carcinoma (LNCaP), and non-cancerous human normal prostate (PNT2) cells as the normal control. Cytotoxicity at different concentrations (1.95, 3.90, 7.81, 15.62, 31.25, 62.5, 125 and 250μg/ml) of these extracts was evaluated using a resazurin assay. B. spectabilis extracts and its isolated constituents pinitol (Bs-1), allantoin (Bs-2) and trigonelline (Bs-3) showed no cytotoxic activity on any of the cell lines. Similarly, A. graecorum extracts and its isolated constituent narcissin (Ag-1) showed no cytotoxic activity. The EtOAc extract of R. raetam was toxic to HepG2, A375, PANC-1 and PNT2 at 250 μg/ml with IC50 values of 139.2 μg/ml, 143.9 μg/ml, 129.1 μg/ml, and 154.3 μg/ml, respectively, and was also toxic to LNCaP at 125 μg/ml with an IC50 value of 67.6 μg/ml. However, this extract was not toxic to A549 and MCF7 cells. In addition, alpinumisoflavone (Rr-1) was toxic against HepG2, A375, A549, PANC-1, MCF7 and PNT2 at 125 μg/ml with IC50 values of 63.9 μg/ml, 64.2 μg/ml, 118.8 μg/ml, 64.1 μg/ml, 72.9 μg/ml, and 112.6 μg/ml respectively, while it was highly toxic to LNCaP at 62.5 μg/ml with an IC50value of 43.6 μg/ml. The n-hexane, MeOH, 8-β-D-glucopyranosylgenistein (Rr-2) and ephedroidin (Rr-3) exhibited no cytotoxic activity on the cell lines. Fraction 2 of P. plicata EtOH extract (PpFr-2) which contains plicatin A (Pp-1), daidzein (Pp 3), and a mixture of psoralen (Pp-2a) and angelicin (Pp-2b) was toxic against all the cell lines. It was toxic to HepG2, PANC-1, and PNT2 at 250 μg/ml with IC50 values of 161.5 μg/ml, 125.9 μg/ml, and 126.1 μg/ml respectively, and was toxic against A375 at 125 μg/ml with an IC50 value of 118.0 μg/ml, while it was highly toxic against MCF7 and LNCaP at 62.5 μg/ml with IC50 values of 51.2 μg/ml, 34.7 μg/ml, respectively. However, this extract was not toxic to A549, while the other fractions demonstrated no cytotoxic activity on the cell lines. In further studies, Rr-1 and PpFr-2 showed selective activity on LNCaP and MCF7 cells. Both Rr-1 and PpFr-2 had an inhibitory effect on adhesion, migration on LNCaP and MCF7 cells. The effect of Rr-1and PpFr-2 inhibited adhesion of LNCaP and MCF7 cells to fibronectin. The % of inhibition of adhesion on LNCaP and MCF7 was 60% -75% and 50% -80% respectively, while the % of inhibition of migration was 50% -70% and 75%-90% respectively. Therefore, Rr-1and PpFr-2 have the potential to treat prostate and breast cancer by inhibition of cell adhesion and migration as a result of reduced or inhibited attachment to fibronectin.
|Date of Award||6 Oct 2021|
- University Of Strathclyde
|Supervisor||Valerie Ferro (Supervisor) & Alexander Gray (Supervisor)|