Reversal of Multidrug Resistance by Morning Glory Resin Glycosides in Human Breast Cancer Cells

Abstract

Reversal of multidrug resistance (MDR) by thirty resin glycosides from the morning glory family (Convolvulaceae) was evaluated in vinblastine-resistant human breast carcinoma cells (MCF-7/Vin). The effects of these amphipathic compounds on the cytotoxicity and P-glycoprotein (P-gp)-mediated MDR were estimated with the sulforhodamine B colorimetric assay. Active noncytotoxic compounds exerted a potentiation effect of vinblastine susceptibility by 1- to over 1906-fold at tested concentrations of 5 and 25 μg/mL. Murucoidin V (1) enhanced vinblastine activity 255-fold when incorporated at 25 μg/mL and also, based on flow cytometry, significantly increased the intracellular accumulation of rhodamine 123 with the use of reserpine as a positive control for a MDR reversal agent. Incubation of MCF-7/Vin cells with 1 caused an increase in uptake and notably lowered the efflux rate of rhodamine 123. Decreased expression of P-glycoprotein by compound 1 was detected by immunofluorescence flow cytometry after incubation with an anti-P-gp monoclonal antibody. These results suggest that resin glycosides represent potential efflux pump inhibitors for overcoming MDR in cancer therapy.

Resistance-modifying Activity in Vinblastine-resistant Human Breast Cancer Cells by Oligosaccharides Obtained from Mucilage of Chia Seeds (Salvia hispanica)

“…The non‐cytotoxic compounds 1 – 4 at a concentration of <29.2 μM exerted moderate potentiation of vinblastine susceptibility with a reversal factor (RF MCF7/Vin + ) around 4.55‐fold for compound 2 , 5.77‐fold for compounds 1 and 3 , and 6.82‐fold for compound. This potency in the reversal of the susceptibility to vinblastine was similar than the activity of reserpine (RF 3.0), a cytotoxic positive efflux pump control (Cruz‐Morales et al, ; Figueroa‐González et al, ; Corona‐Castañeda et al, ). All compounds did not possess cytotoxic activity against carcinoma cell lines (IC 50 > 29.2 μM).…”

“…For the first cytotoxic assay, colon (HCT‐15 and HCT‐116), cervix (HeLa), and breast (MCF7 and MDA‐MB‐231) carcinoma cell lines were acquired from the American Type Culture Collection. The resistant counterpart MCF7/Vin was developed and subcultured during five consecutive years, as previously reported (Figueroa‐González et al, ; Corona‐Castañeda et al, ). All cells lines were maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum and cultured at 37°C in an atmosphere of 5% CO 2 in air (100% humidity).…”

“…In these experiments, reserpine (5 μg/mL) was used as a positive control. The reversal fold (RF) value, as a parameter of potency, was calculated from dividing the IC 50 of vinblastine alone by the IC 50 of vinblastine in the presence of test compounds (Cruz‐Morales et al, ; Figueroa‐González et al, ; Corona‐Castañeda et al, ).…”

Dereplication of podophyllotoxin and related cytotoxic lignans in Hyptis verticillata by ultra‐high‐performance liquid chromatography tandem mass spectrometry

“…The cytotoxicity measurements were determined by using the SRB assay against breast (MCF‐7) carcinoma cell lines as described previously . In brief, cell lines were maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum and cultured at 37°C in 5% CO 2 in air (100% humidity).…”

“…The cytotoxicity measurements were determined by using the SRB assay against breast (MCF-7) carcinoma cell lines as described previously. 28 In brief, cell lines were maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum and cultured at 37°C in 5% CO 2 in air (100% humidity). Cells at log phase were treated in triplicate with test samples (0.2-25 μg/mL) and incubated for 72 h. Results are expressed as the concentration that inhibits 50% control growth after the incubation period (IC 50 ).…”