Chrysosplenetin, in the absence and presence of artemsininin, alters breast cancer resistance protein-mediated transport activity in Caco-2 cell monolayers using aristolochic acid I as a specific probe substrate
AUTOR(ES)
Zhang, Yuanyuan, Zhang, Chenxu, Chen, Jie, Ma, Liping, Yang, Bei, Wang, Jianhuan, Wu, Xiuli, Chen, Jing
FONTE
Rev. bras. farmacogn.
DATA DE PUBLICAÇÃO
2017-12
RESUMO
ABSTRACT The present study describes the impact of chrysosplenetin, in the absence and presence of artemisinin, on in vitro breast cancer resistance protein-mediated transport activity in Caco-2 cell monolayers using aristolochic acid I as a specific probe substrate. We observed that novobiocin, a known breast cancer resistance protein active inhibitor, increased Papp (AP-BL) of aristolochic acid I 3.13 fold (p < 0.05) but had no effect on Papp (BL-AP). Efflux ratio (PBA/PAB) declined 4.44 fold (p < 0.05). Novobiocin, consequently, showed a direct facilitation on the uptake of AAI instead of its excretion. Oppositely, both artemisinin and chrysosplenetin alone at dose of 10 µM significantly decreased Papp (BL-AP) instead of Papp (AP-BL). Chrysosplenetin alone attenuated the efflux ratio, which was suggestive of being as a potential breast cancer resistance protein suppressant. Oddly, Papp (BL-AP) as well as efflux ratio were respectively enhanced 2.52 and 2.58 fold (p < 0.05), when co-used with artemisinin and chrysosplenetin in ratio of 1:2. The potential reason remains unclear; it might be relative to binding sites competition between artemisinin and chrysosplenetin or the homodimer/oligomer formation of breast cancer resistance protein bridged by disulfide bonds, leading to an altered in vitro breast cancer resistance protein-mediated efflux transport function.
Documentos Relacionados
- Tobacco mosaic virus movement protein-mediated protein transport between trichome cells.
- Carrier Protein-mediated Transport of Neutral Amino Acids into Mung Bean Mitochondria
- Impact of chrysosplenetin, per se or in combination with artemisinin, on breast cancer resistance protein (Bcrp)/ABCG2 mRNA expression levels in mice small intestine
- Protein-mediated surface structuring in biomembranes
- Tailed duplex DNA is the preferred substrate for Rad51 protein-mediated homologous pairing