Table 1.
Some examples of natural inhibitors of P-glycoprotein in leukemia cell lines.
| P-gp Natural Inhibitors “Fourth Generation” |
Mechanism of Action |
|---|---|
| Flavonoids | |
| Quercetin | Inhibition of P-gp gene expression in adryamicin-resistant human chronic myeloid leukemia cell line (K562/ADR) [31]. |
| Wogonin | Inhibition of P-gp expression in a human acute myeloid leukemia cell line (HL-60) [32]. |
| Grape seed proanthocyanidin extract (GSPE) | GSPE inhibits P-gp expression via the PI3K / Akt signal transduction pathway in adryamicin-resistant human acute myeloid leukemia cell line (HL-60/ADR) [33]. |
| Curcumin | Inhibition of P-gp mediated efflux in a doxorubicin-resistant human chronic myeloid leukemia cell line (K562/Dox) [34,35]. |
| Alkaloids | |
| Pervilleine A | Inhibition of P-gp gene expression in a multidrug-resistant human T-cell childhood acute lymphocytic leukemia cell line (CEM/VLB100) [36]. |
| Lobeline | Inhibition of P-gp mediated efflux probably by substrate competition in a multidrug-resistant human T-cell childhood acute lymphocytic leukemia cell line (CEM/ADR5000) [37]. |
| harmine, and sanguinarine | Inhibition of P-gp gene expression in a multidrug-resistant human T-cell childhood acute lymphocytic leukemia cell line (CEM/ADR5000) [38]. |
| Berbamine | Inhibition of mRNA and P-gp protein expression in an imatinib-resistant BCR-ABL-positive chronic myeloid leukemia cell line (K562-r) [39]. |
| Reserpine and yohimbine | Inhibition of P-gp mediated efflux in a multidrug-resistant human T-cell childhood acute lymphocytic leukemia cell line (CEM/VLB100) [40]. |
| Bromocriptine | Inhibition of the overexpressed P-gp protein in a vinblastine-resistant human chronic myeloid leukemia cell line (K562/R10) [41]. |
| Isoquinoline alkaloid chelidonine | Inhibition of P-gp mediated efflux in multidrug-resistant human T-cell childhood acute lymphocytic leukemia cell line (CEM/DOX5000) [20]. |
| Terpenoids | |
| Limonin | Inhibition of P-gp mediated efflux in a multidrug-resistant human T-cell childhood acute lymphocytic leukemia cell lines (CCRF-CEM and CEM/ADR5000) [42]. |
| Euphodendroidin D and Pepluanin A |
Inhibition of P-gp mediated efflux via binding with its active sites in a daunomycin-resistant human chronic myeloid leukemia cell line (K562/R7) [43]. |
| Lupeol | Inhibition of mRNA and P-gp protein expression in a doxorubicin-resistant human acute myeloid leukemia cell line (HL-60R) [44,45]. |
| Phytol and heptacosane | Inhibition of P-gp mediated efflux via binding with the DBP site, in a similar way to verapamil, in a doxorubicin-resistant human acute myeloid leukemia cell line (HL-60R) [46]. |
| Saponins | |
| Ginsenoside F1 | Inhibition of P-gp mediated efflux in daunorubicin- and doxorubicin-resistant acute myeloid leukemia sublines (AML-2/D100 and AML-2/DX100) [47]. |
| Gracillin | Inhibition of P-gp mediated efflux via direct interaction with active binding sites in a daunorubicin-resistant human chronic myeloid leukemia cell line (K562/R7) [48]. |
| Pinnatasterone | Inhibition of P-gp mediated efflux via binding with its active sites in a daunomycin-resistant human chronic myeloid leukemia cell line (K562/R7) [49]. |
CEM/VLB100 derived from CCRF-CEM cells with selection for vinblastine resistance; CEM/DOX5000 derived from CCRF-CEM cells with selection for doxorubicin resistance; CEM/ADR5000 derived from CCRF-CEM cells with selection for adriamycin resistance; AML-2/D100 and AML-2/DX100 derived from acute myeloid leukemia (OCI/ AML-2) cells with selection for daunorubicin and for doxorubicin resistances, respectively.