Constituents and Anti-Multidrug Resistance Activity of Taiwanofungus camphoratus on Human Cervical Cancer Cells
Abstract
Resistance to anti-cancer drugs is one of the main factors of treatment failure resulting in high morbidity. Among the reasons of resistance, overexpression of efflux pumps leading to multidrug resistance is an important issue that needs to be solved. Taiwanofungus camphoratus has been used as a nutritional supplement to treat various cancers. However, its effects on the resistance to chemotherapeutic agents are still unknown. In this study, we report four new chemical constituents of T. camphoratus isolated from an ether extract: camphoratins K (1) and N (2) and benzocamphorins G (3) and I (4). Furthermore, we evaluated zhankuic acids A-C for their P-glycoprotein (P-gp) inhibitory effects. The results showed that zhankuic acid A was the most potent P-gp inhibitor compound and (at 20 μM) could reverse drug resistance in human cancer cells, restoring an IC50 of 78.5 nM for doxorubicin, of 48.5 nM for paclitaxel, and of 321.5 nM for vincristine, indicating a reversal fold of 48, 38, and 45 times, respectively. This study provides support for the use of T. camphoratus in the further development of cancer therapy.
Figures 
Figure 1
Structure of camphoratin K (…
Figure 1
Structure of camphoratin K ( 1 ) ( a ) and its key…
Figure 1 Structure of camphoratin K (1) (a) and its key COSY (b), HMBC (c), and NOESY (d) correlations.
Figure 2
Structure of camphoratin N (…
Figure 2
Structure of camphoratin N ( 2 ) ( a ) and its key…
Figure 2 Structure of camphoratin N (2) (a) and its key HMBC (b) and NOESY (c) correlations.
Figure 3
Structure of benzocamphorin G (…
Figure 3
Structure of benzocamphorin G ( 3 ) ( a ) and its key…
Figure 3 Structure of benzocamphorin G (3) (a) and its key HMBC (b) and NOESY (c) correlations.
Figure 4
Structure of benzocamphorin I (…
Figure 4
Structure of benzocamphorin I ( 4 ) ( a ) and its key…
Figure 4 Structure of benzocamphorin I (4) (a) and its key HMBC (b) and NOESY (c) correlations.
Figure 5
The inhibitory effects of the…
Figure 5
The inhibitory effects of the methanol extract at 10 and 20 μM concentrations…
Figure 5 The inhibitory effects of the methanol extract at 10 and 20 μM concentrations (TAM 10, TAM 20), the EtOAc layer (TAE 10, TAE 20), the water layer (TAW 10, TAW 20) and verapamil at 2.5 μM concentration (VER 2.5) on P-glycoprotein (P-gp) in ABCB1/Flp-InTM-293 cells. * denotes p < 0.05 compared with the intracellular calcein fluorescence in the control group. The numbers, 2.5, 10, 20, indicate the μM concentrations.
Figure 6
The concentration-dependent inhibitory effects of…
Figure 6
The concentration-dependent inhibitory effects of zhankuic acids (ZAs) A, B, C on P-gp…
Figure 6 The concentration-dependent inhibitory effects of zhankuic acids (ZAs) A, B, C on P-gp in ABCB1/Flp-InTM-293 cells. * denotes p < 0.05 compared with the intracellular calcein fluorescence in control group.