Ling-Zhi polysaccharides potentiate cytotoxic effects of anticancer drugs against drug-resistant urothelial carcinoma cells.
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 mug/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-x(L) down-regulatuion, and cytochrome c release.
Huang
Chao-Yuan
CY
Department of Urology, National Taiwan University Hospital, and College of Medicine, National Taiwan University, Taipei, Taiwan.
Chen
Jeff Yi-Fu
JY
Wu
Jia-En
JE
Pu
Yeong-Shiau
YS
Liu
Guang-Yaw
GY
Pan
Min-Hsiung
MH
Huang
Ying-Tang
YT
Huang
A-Mei
AM
Hwang
Chi-Ching
CC
Chung
Shu-Ju
SJ
Hour
Tzyh-Chyuan
TC
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D006801:Humans; D011134:Polysaccharides / Q000494:pharmacology*; D020940:Reishi / Q000737:chemistry*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000503:physiopathology*
D000970:Antineoplastic Agents; D011134:Polysaccharides