Effects of 19 Herbal Extracts on the Sensitivity to Paclitaxel or 5-Fluorouracil in HeLa Cells

Abstract

The popularity of traditional herbal medicine (THM) being used as complementary medicines or alternative medicines is increasing. On the other hand, the development of multidrug resistance (MDR) remains a major hurdle to successful cancer chemotherapy. Some THMs capable of reversing MDR may contribute to the improvement of clinical outcomes in cancer chemotherapy. Herein, 19 kinds of herb were chosen from the ingredients of major THMs, and their effects on the sensitivity to anticancer drugs of tumor cells were investigated using the human cervical carcinoma HeLa cells. Focusing on the major mechanism for MDR, i.e., MDR1/P-glycoprotein, the effects of herbal extracts on its transport function were also examined using a MDR1 substrate Rhodamine123. Glycyrrhizae Radix, Rhei Rhizoma, Scutellariae Radix, Poria, Zizyphi Fructus, Zingiberis Rhizoma (dry), Coptidis Rhizoma, Ephedrae Herba and Asiasari Radix significantly enhanced the sensitivity to a MDR1 substrate paclitaxel, whereas none of the herbal extracts used had any effect on the sensitivity to 5-fluorouracil, which is not a substrate for MDR1. Rhodamine123 uptake was significantly increased by Rhei Rhizoma, Poria or Ephedrae Herba among nine herbal extracts sensitized to paclitaxel. This suggests that the increase in paclitaxel sensitivity by Glycyrrhizae Radix, Rhei Rhizoma, Poria or Ephedrae Herba was caused, in part, by the inhibition of MDR1 function, and the change in paclitaxel sensitivity by the other herbal extracts was not always dependent on this. Collectively, these findings indicate that the combination of anticancer drugs with some herbal extracts contributes to the enhancement of clinical outcomes in cancer chemotherapy.

Chan-Yu-Bao-Yuan-Tang and 5-fluorouracil synergistically induce apoptosis by means of the caspase-3 signaling pathway in lung and cervical cancer cells

“…our findings strongly suggest that a combination therapy using CYBYT and 5-Fu may achieve a synergistic effect on lung and cervical cancer. The results obtained were identical to those of previous studies (16,17), which revealed that relatively high concentrations of 5-Fu were required to achieve significant cytotoxic effects against A549 and HeLa cells. These studies evaluated the inhibitory effect of a single herb or its extract on cancer.…”

Effects of Asiasari radix on the morphology and viability of mesenchymal stem cells derived from the gingiva

“…High concentrations of A. radix exerted adverse effects on the gingival stem cells, and a significant reduction in cellular viability was observed at 100 and 1,000 µg/ml A. radix concentrations. The effects of A. radix have been previously analyzed in in vitro and in vivo experiments (4,12,13). One study revealed no significant effect on the growth of HeLa cells following A. radix treatment for 72 h at a range of concentrations between 0.0001 and 1,000 µg/ml (12).…”

“…The effects of A. radix have been previously analyzed in in vitro and in vivo experiments (4,12,13). One study revealed no significant effect on the growth of HeLa cells following A. radix treatment for 72 h at a range of concentrations between 0.0001 and 1,000 µg/ml (12). The safety of an A. radix methanol extract was investigated in an oral sub-acute 28-day toxicity study in Sprague-Dawley rats at doses of 50, 250 and 500 mg/kg/day, and the authors concluded that the methanolic extract of A. radix appeared to be safe and nontoxic within the experimental conditions (4).…”

Differential effects of calcium antagonists on ABCG2/BCRP-mediated drug resistance and transport in SN-38-resistant HeLa cells

“…The effects of calcium antagonists on the sensitivity to mitoxantrone in HeLa and HeLa/SN100 cells were evaluated with a WST-1 assay (13)(14)(15). Cells (1x10 3 / well) were seeded onto 96-well plates in 100 µl DMEM without any drugs.…”