Nuclear matrix protein, prohibitin, was down-regulated and translocated from nucleus to cytoplasm during the differentiation of osteosarcoma MG-63 cells induced by ginsenoside Rg1, cinnamic acid, and tanshinone IIA (RCT).
Ginsenoside Rg1, cinnamic acid, and tanshinone IIA (RCT) are effective anticancer and antioxidant constituents of traditional Chinese herbal medicines of Ginseng, Xuanseng, and Danseng. The molecular mechanisms of anticancer effects of those constituents and their targets are unknown. Prohibitin, an inner membrane-bound chaperone in mitochondrion involved in the regulation of cell growth, proliferation, differentiation, aging, and apoptosis, was chosen as a candidate molecular target because of its frequent up-regulation in various cancer cells. We demonstrated that prohibitin existed in the filaments of the nuclear matrix of the MG-63 cell and its expression was down-regulated by the treatment of RCT using proteomic methodologies and Western blot analysis. Immunogold electro-microscopy also found that prohibitin was localized on nuclear matrix intermediate filaments (NM-IF) that had undergone restorational changes after RCT treatment. Prohibitin may function as a molecular chaperone that might interact with multiple oncogenes and tumor suppressor genes. We found that oncogenes c-myc and c-fos and tumor suppressor genes P53 and Rb were regulated by RCT as well and that these gene products co-localized with prohibitin. Our study identified prohibitin as a molecular target of the effective anticancer constituents of Ginseng, Xuanseng, and Danseng that down-regulated prohibitin in nuclear matrix, changed prohibtin trafficking from nucleolus to cytoplasm, and regulated several oncogenes and tumor suppressor genes. Prohibitin downregulation and cellular trafficking from nucleolus to cytoplasm indicated RCT protective roles in cancer prevention and treatment.
Shi
Song-Lin
SL
The Key Laboratory of Ministry of Education for Cell Biology & Tumor Cell Engineering, School of Life Science, Xiamen University, Xiamen 361005, P.R. China.
Li
Qi-Fu
QF
Liu
Qing-Rong
QR
Xu
Dong-Hui
DH
Tang
Jian
J
Liang
Ying
Y
Zhao
Zhen-Li
ZL
Yang
Li-Ming
LM
D045784:Abietanes; D000970:Antineoplastic Agents / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001692:Biological Transport; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D002934:Cinnamates / Q000494:pharmacology*; D003593:Cytoplasm / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D036145:Ginsenosides / Q000494:pharmacology*; D006801:Humans; D009857:Oncogenes; D010616:Phenanthrenes / Q000494:pharmacology*; D000091402:Prohibitins; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D012097:Repressor Proteins / Q000096:biosynthesis*; D016160:Retinoblastoma Protein / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D045784:Abietanes; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D002934:Cinnamates; D036145:Ginsenosides; D010616:Phenanthrenes; D000091402:Prohibitins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53; C021751:tanshinone; C029010:cinnamic acid; C035054:ginsenoside Rg1