Ling-Zhi Polysaccharides Potentiate Cytotoxic Effects of Anticancer Drugs against Drug-Resistant Urothelial Carcinoma Cells
2010
Huang, Chao-Yuan | Chen, Jeff Yi-Fu | Wu, Jia-En | Pu, Yeong-Shiau | Liu, Guang-Yaw | Pan, Min-Hsiung | Huang, Ying-Tang | Huang, A-Mei | Hwang, Chi-Ching | Chung, Shu-Ju | Hour, Tzyh-Chyuan
The combined effects of ling-zhi polysaccharide fraction 3 (LZP-F3) and anticancer drugs (cisplatin and arsenic trioxide) were examined in three human urothelial carcinoma (UC) cells (parental, NTUB1; cisplatin-resistant, N/P(14); and arsenic-resistant, N/As(0.5)). MTT assay and median-effect analysis revealed that LZP-F3 could profoundly reverse the chemosensitivity of N/P(14) and N/As(0.5) to cisplatin and arsenic, respectively, in a dose-dependent manner, which involved activation of p38 and down-regulation of Akt and XPA. A dose of 10 μg/mL of LZP-F3 induced significant G1 arrest in N/P(14) and N/As(0.5) cells by flow cytometry, which may be mediated by the induction of p21(WAF1/CIP1). The combination of LZP-F3 and arsenic trioxide produced a significant synergistic growth inhibition of NTUB1 and N/As(0.5) cells. Similar results were also found in N/P(14) cells. These molecular events of combined effects involved significant and earlier induction of Fas, caspase 3 and 8 activation, Bax and Bad up-regulation, Bcl-2 and Bcl-xL down-regulatuion, and cytochrome c release.
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