title: Betulinic acid promotes TRAIL function on liver cancer progression inhibition through p53/Caspase-3 signaling activation.
abstract: Betulinic acid (BA), isolated from the tree bark, is a pentacyclic triterpenoid, showing inhibitory role in cancer cells. However, the effects of BA treatment on liver cancer have little to be known. Thus, the study is conducted to explore the in vitro and in vivo role of BA in liver cancer. And the interactions between BA and tumor necrosis factor-related apoptosis-inducing ligand of APO2, also known as TRAIL, were investigated in liver cancer cells. A synergistic effect of BA and APO2 combination on apoptosis induction in liver cancer cells was observed. The cancer cells were insensitive to APO2 single therapy. However, liver cancer cells receiving BA were sensitive to APO2-triggered apoptotic response by enhancing Caspases cleavage, due to elevation of decoy receptor 1 and 2 (DcR1 and DcR2) dependent on p53. Bcl-2 family members of Bcl-2 and Mcl-1, belonging to anti-apoptosis, were decreased, whereas Bad and Bak, as pro-apoptotic members, were increased for BA and APO2 combined treatment. Additionally, the mouse xenograft model suggested that BA and APO2 in combination markedly inhibited liver cancer growth in comparison to BA or APO2 monotherapy without toxicity. The present study revealed a dramatically therapeutic strategy for promoting APO2-induced anti-cancer effects on liver cancer cells via BA combination.
authors.affiliation: Huai'an First People's Hospital, Nanjing Medical University, No. 6 Beijing West Road, Huaiyin District, Huai'an, Jiangsu 223300, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Huai'an Fourth People's Hospital, No.128 Yan'an East Road, Qingpu District, Huai'an, Jiangsu 223300, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Huai'an First People's Hospital, Nanjing Medical University, No. 6 Beijing West Road, Huaiyin District, Huai'an, Jiangsu 223300, China.
authors.forename: Qian-Jun
authors.initials: QJ
authors.lastname: Li
authors.affiliation: Huai'an First People's Hospital, Nanjing Medical University, No. 6 Beijing West Road, Huaiyin District, Huai'an, Jiangsu 223300, China.
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Feng
authors.affiliation: Huai'an First People's Hospital, Nanjing Medical University, No. 6 Beijing West Road, Huaiyin District, Huai'an, Jiangsu 223300, China. Electronic address: panfeng223300@qq.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D053148:Caspase 3 / Q000187:drug effects*; D045744:Cell Line, Tumor; D058851:GPI-Linked Proteins / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D053978:Pentacyclic Triterpenes; D053320:Receptors, Tumor Necrosis Factor, Member 10c / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000187:drug effects / Q000378:metabolism*; D014315:Triterpenes / Q000494:pharmacology*; D053319:Tumor Necrosis Factor Decoy Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014410:Tumor Stem Cell Assay; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays; D000094062:Betulinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D058851:GPI-Linked Proteins; D053978:Pentacyclic Triterpenes; D053320:Receptors, Tumor Necrosis Factor, Member 10c; D053221:TNF-Related Apoptosis-Inducing Ligand; C108661:TNFRSF10C protein, human; C451501:TNFRSF10D protein, human; C505653:TNFSF10 protein, human; D014315:Triterpenes; D053319:Tumor Necrosis Factor Decoy Receptors; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; C505407:CASP3 protein, human; D053148:Caspase 3; D000094062:Betulinic Acid
keywords: APO2; Betulinic acid; Caspases; Liver cancer; p53