title: Chan-Yu-Bao-Yuan-Tang and 5-fluorouracil synergistically induce apoptosis by means of the caspase-3 signaling pathway in lung and cervical cancer cells.
abstract: Previous clinical studies have shown the safety and efficacy of the traditional Chinese medicinal herbal aqueous extract Chan-Yu-Bao-Yuan-Tang (CYBYT) for the treatment of lung and cervical cancer patients. Used in combination with 5-fluorouracil (5-Fu), CYBYT has been observed to be particularly effective in cancer treatment. Herein, the combined anticancer effect and the underlying mechanisms of 5-Fu and CYBYT in the human lung cancer cell line A549 and the human cervical cancer cell line HeLa were investigated in vitro. The MTT assay, Annexin V-FITC staining and Western blotting were applied to identify cell viability, the stages of apoptosis and the expression of signaling proteins, respectively. The results indicated that CYBYT and 5-Fu, alone or in combination, significantly inhibited proliferation and induced marked apoptosis in A549 and HeLa cells, but had no significant inhibitory effects on normal human IMR-90 fibroblasts. The rate of mid and late apoptosis or necrosis was greater after 5-Fu treatment compared to treatment with CYBYT or the combination of agents; however, the early apoptotic rate showed opposite results. CYBYT and 5-Fu, alone or in combination, up-regulated cleaved caspase-3 expression in a time-dependent manner, with CYBYT being more effective than 5-Fu. Taken together, our data show that the pro-apoptotic activity of the two-drug combination was much stronger than that of CYBYT or 5-Fu alone; CYBYT combined with 5-Fu had synergistic effects at lower concentrations and promoted apoptosis, while the combined treatment also decreased the cytotoxic side effects of 5-Fu.
authors: Joint Laboratory of Immunogenomics, Zhoushan Hospital - Beijing Institute of Genomics, Chinese Academy of Sciences, Zhoushan, Zhejiang 316004, PR China.
authors: Fang
authors: F
authors: Zeng
authors: Xiaoguang
authors: X
authors: Liu
authors: Yuncheng
authors: Y
authors: Li
authors: Gang
authors: G
authors: Chen
authors: Yekai
authors: Y
authors: Wang
authors: Shiquan
authors: S
authors: Zhou
authors: Wangyu
authors: W
authors: Zhu
authors: Yanyan
authors: Y
authors: Huang
authors: Jiehang
authors: J
authors: Zhou
authors: Shibo
authors: S
authors: Li
authors: Yongkui
authors: Y
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D000970:Antineoplastic Agents; D004365:Drugs, Chinese Herbal; C569176:chan-yu-bao-yuan-tang; D053148:Caspase 3; D005472:Fluorouracil