Paclitaxel-Containing Extract Exerts Anti-Cancer Activity through Oral Administration in A549-Xenografted BALB/C Nude Mice: Synergistic Effect between Paclitaxel and Flavonoids or Lignoids

Abstract

Taxus yunnanensis is a paclitaxel-containing herb with traditional usage in cancer treatment, and its extract possesses great oral bioavailability of paclitaxel. However, it is elusive whether paclitaxel-containing extract (HDS-1) can exert anti-tumor effect through oral administration and how other components contribute to its efficacy. Therefore, we investigate the oral-route anti-tumor effect of HDS-1 in A549-bearing mice. HDS-1-derived flavonoids (HDS-2) and lignoids (HDS-3) are hypothesized to contribute to HDS-1’s efficacy, and their effects of enhancing enterocytic absorption and cytotoxicity of paclitaxel are validated in 2 permeability experiments and apoptosis-related assay, respectively. In vivo, A549 growth is significantly inhibited by 86.1 ± 12.94% ( P < 0.01 ) at 600 mg/kg of HDS-1 and 65.7 ± 38.71% ( P < 0.01 ) at 200 mg/kg. HDS-2 and HDS-3 significantly reduce the efflux ratio of paclitaxel to 2.33 and 3.70, respectively, in Caco-2 permeability experiment and reduce paclitaxel reflux in MDCK-MDR1 experiment. Furthermore, HDS-2 and HDS-3 potentiated paclitaxel-induced cytotoxicity by 19.1–22.45% ( P < 0.05 ) and 10.52–18.03% ( P < 0.05 ), respectively, inhibited the expression of cyclinB1, Bcl-2, and pMCL-1, and increased the percentage of necrosis cell in the condition of paclitaxel exposure. Conclusively, paclitaxel-containing extracts exert anti-cancer effects through oral administration, and flavonoid and lignoids contribute to its anti-cancer effect through simultaneously improving enterocytic absorption of paclitaxel and the cytotoxic effect of paclitaxel.

Synergistic effects of flavonoids and paclitaxel in cancer treatment: a systematic review

“…An anticancer effect is observed in nude A549-bearing mice that receive the paclitaxel-containing extract. HDS-1-derived flavonoids and lignoids, in addition to improving the rate at which paclitaxel is absorbed by enterocytes, significantly increase the level of cell death caused by BCL-2 [ 135 ].…”

“…Therefore, it is possible to use HDS-1 long-term as cancer treatment under appropriate dose adjustments. Research on the fundamentals of Chinese medicine places an emphasis on the complementary roles played by active and supportive ingredients [ 135 ].…”

Natural Taxanes: From Plant Composition to Human Pharmacology and Toxicity

“…In an animal study, it was observed that orally administered PTX together with T. yunnanensis extract increased its pharmacokinetic parameters (area under curve (AUC) and maximum serum concentration (C max )) due to the inhibition of PTX efflux in the gastrointestinal tract. In addition, it was later observed that this extract potentiates PTX-induced cytotoxicity, i.e., exerts an anti-cancer effect through oral administration [ 16 ]. Similarly, it was also observed in the combination of PTX with other extracts from Taxus spp.…”