title: Restoration of the tumor-suppressor function to mutant p53 by Ganoderma lucidum polysaccharides in colorectal cancer cells.
abstract: Ganoderma lucidum polysaccharides (GLPs), isolated from spores, mycelia and fruiting bodies of Ganoderma lucidum, have been suggested to possess anticancer activities in a large number of basic studies. A recent survey revealed that GLP-induced inhibition of cancer cell growth was dependent on the existence of functional p53. However, the actual role of p53-mediated tumor-suppressing pathways in facilitating the anticancer effect of GLPs is still unclear. In the present study, we investigated the interaction between GLPs and mutant p53 that exists in more than half of the known types of cancers. Our results showed that GLPs reactivated mutant p53 in colorectal cancer HT29 (p53R273H) and SW480 (p53R273H&P309S) cells while applied alone or together with 5-fluorouracil (5-FU). This reactivation further induced cell growth inhibition and apoptosis. In addition, western blot assay and in vitro cell-free apoptosis assay suggested that the activation of mutant p53 was effective in both a transcriptional-dependent and -independent pathway. Altogether, our data demonstrated for the first time that GLPs show prominent anticancer activities by reactivating several types of mutant p53. Therefore, targeting mutant p53 by GLPs alongside other chemotherapeutics may be considered as a novel treatment strategy for cancer.
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Jiang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Lingyao
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhao
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Zhaoyu
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Renxia
authors.initials: R
authors.lastname: Zhang
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Jingji
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Cai
authors.affiliation: School of Life Sciences, Jilin University, Changchun, Jilin 130012, P.R. China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D016147:Genes, Tumor Suppressor / Q000187:drug effects / Q000502:physiology; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D050505:Mutant Proteins / Q000187:drug effects / Q000502:physiology; D011134:Polysaccharides / Q000302:isolation & purification / Q000494:pharmacology*; D020940:Reishi / Q000737:chemistry*; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects* / Q000235:genetics*
chemical_list: D050505:Mutant Proteins; D011134:Polysaccharides; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D005472:Fluorouracil