Reversal Effects of Components from the Fruits of Illicium simonsii on Human Adriamycin‐resistant MCF‐7 and 5‐Fluorouracil‐resistant Bel7402 Cells

Abstract

Twenty-one compounds including seven characteristic sesquiterpene lactones were isolated from Illicium simonsii and screened in vitro for their potential to restore the sensitivity of Adriamycin (ADR) resistant breast cancer cells (MCF-7/ADR) and 5-fluorouracil-resistant hepatocellular carcinoma cells (Bel7402/5-FU) to ADR and 5-fluorouracil, respectively. These compounds were found to be non-toxic to a panel of tumour cell lines: human breast cancer cells (MCF-7), cervical cancer cells (HeLa), hepatic liver carcinoma cells (HepG-2, Bel7402) and gastric carcinoma cells (BGC-823, SGC-7901). Five compounds showed an obvious decrease in the IC(50) of doxorubicin in MCF-7/ADR and four compounds sensitized Bel7402/5-FU to 5-fluorouracil at non-toxic concentrations. The relationship between the structure of these non-cytotoxic substances and their multidrug-resistant (MDR) reversal abilities was investigated by principal component analysis (PCA) of the reversing fold (RF) values of these compounds and their calculated molecular descriptors of the tested substances. No correlations were found between the reversal potencies of these compounds to the two MDR cells. Compounds with lower polarity generally had stronger sensitizing ability to the P-glycoprotein (Pgp) overexpressed MCF-7/ADR cells. On the other hand, higher hydrophilic compounds seemed to exhibit a stronger reversal effect to the MDR-associated protein (MRP) overexpressed Bel7402/5-FU cell line. Our findings favoured further investigations on the active substances and the underlying mechanisms.

Natural Product Modulators to Overcome Multidrug Resistance In Cancer

“…Compounds with lower polarity generally had stronger sensitizing ability to the Pgp overexpressed in adriamycin resistant breast cancer cells. On the other hand, higher hydrophilic compounds seemed to exhibit a stronger reversal effect to the MRP overexpressed in 5-fluorouracil-resistant hepatocellular carcinoma cells (119). It has been shown that miRNAs play a critical role in drug transport and MDR (120).…”

Java brucea and Chinese herbal medicine for the treatment of cholesterol granuloma in the suprasellar and sellar regions

“…[ 35 ] Another 2 components (Zedoary and Oldenlandia diffusa) also exhibit potential anticancer effects and restore the sensitivity of MCF-7/ADR (doxorubicin-resistant MCF-7 breast cancer cells) and A549/Taxol cells, modulating the multidrug resistance phenotype and the function of P-glycoprotein in human breast cancer cells. [ 36 , 37 ]…”

Clinically-Relevant ABC Transporter for Anti-Cancer Drug Resistance

“…It can competitively inhibit the transport function of P-gp without interrupting ATP hydrolysis, and increase the intracellular accumulation of many anticancer drugs to overcome the P-gpmediated MDR (Wang and Sun, 2020). Indole alkaloids such as Reserpine ( 10), Indole-3-carbinol and indole-3-carbaldehyde can inhibit P-gp mediated efflux of drugs like doxorubicin, vincristine (Henrich et al, 2006;Wei et al, 2012). 3,4,5-trimethoxybenzyl leuconicine A (11), a derivative of leuconicine A, is a potent P-gp inhibitor as it decreases the dose of vincristine in a resistant cancer cell lines (Munagala et al, 2014).…”