Six flavonoids present in Pulicaria jaubertii,
i.e., 7,3′-di-O-methyltaxifolin (1), 3′-O-methyltaxifolin (2),
7-O-methyltaxifolin (3), taxifolin (4), 3-O-methylquercetin (5),
and quercetin (6), were tested for their anticancer activities.
The methylated flavonoids, compounds 1–3 and 5, were evaluated for their anticancer activities
in comparison to the non-methylated parent flavonoids taxifolin (4) and quercetin (6). The structures of the known
compounds were reconfirmed by spectral analyses using 1H and 13C NMR data comparisons and HRMS spectrometry.
The anticancer activity of these compounds was evaluated in colon
cancer, HCT-116, and noncancerous, HEK-293, cell lines using the MTT
antiproliferative assays. The caspase-3 and caspase-9 expressions
and DAPI (4′, 6-diamidino-2-phenylindole) staining assays were
used to evaluate the apoptotic activity. All the compounds exhibited
antiproliferative activity against the HCT-116 cell line with IC50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15,
32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 μg/mL for
compounds 1 to 6, respectively. All the
compounds produced a significant reduction in HCT-116 cell line proliferation,
except compounds 2 and 6. The viability
of the HEK-293 normal cells was found to be significantly higher than
the viability of the cancerous cells at all of the tested concentrations,
thus suggesting that all the compounds have better inhibitory activity
on the cancer cell line. Apoptotic features such as chromatin condensation
and nuclear shrinkage were also induced by the compounds. The expression
of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after
48 h of treatment, suggesting cell death by the apoptotic pathways.
The molecular docking studies showed favorable binding affinity against
different pro- and antiapoptotic proteins by these compounds. The
docking scores were minimum as compared to the caspase-9, caspase-3,
Bcl-xl, and JAK2.
