TY - JOUR
T1 - Comparative Anticancer Potentials of Taxifolin and Quercetin Methylated Derivatives against HCT-116 Cell Lines
T2 - Effects of O-Methylation on Taxifolin and Quercetin as Preliminary Natural Leads
AU - Mohammed, Hamdoon A.
AU - Almahmoud, Suliman A.
AU - El-Ghaly, El Sayed M.
AU - Khan, Firdos Alam
AU - Emwas, Abdul Hamid
AU - Jaremko, Mariusz
AU - Almulhim, Fatimah
AU - Khan, Riaz A.
AU - Ragab, Ehab A.
N1 - Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/12/20
Y1 - 2022/12/20
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85143860044&partnerID=8YFLogxK
U2 - 10.1021/acsomega.2c05565
DO - 10.1021/acsomega.2c05565
M3 - Article
AN - SCOPUS:85143860044
SN - 2470-1343
VL - 7
SP - 46629
EP - 46639
JO - ACS OMEGA
JF - ACS OMEGA
IS - 50
ER -
