Ling-Zhi Polysaccharides Potentiate Cytotoxic Effects of Anticancer Drugs against Drug-Resistant Urothelial Carcinoma Cells

• Published in: Journal of agricultural and food chemistry 2010-08, Vol.58 (15), p.8798-8805
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: antineoplastic agents; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Biological and medical sciences; carcinoma; Carcinoma - drug therapy; Carcinoma - physiopathology; cell culture; Cell Line, Tumor; Cell Proliferation - drug effects; cytotoxicity; drug adjuvants; drug resistance; Drug Resistance, Neoplasm; Drug Synergism; Drug Therapy, Combination; Food Chemistry/Biochemistry; Food industries; functional foods; Fundamental and applied biological sciences. Psychology; human cell lines; Humans; Ling-Zhi mushrooms; mushrooms; polysaccharides; Polysaccharides - pharmacology; Reishi - chemistry; synergism; Urinary Bladder Neoplasms - drug therapy; Urinary Bladder Neoplasms - physiopathology; urinary tract; urothelial carcinoma cells
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf1020158

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 p21WAF1/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.