title: Dendrosomal curcumin nanoformulation modulate apoptosis-related genes and protein expression in hepatocarcinoma cell lines.
abstract: The side-effects observed in conventional therapies have made them unpromising in curing Hepatocellular carcinoma; therefore, developing novel treatments can be an overwhelming significance. One of such novel agents is curcumin which can induce apoptosis in various cancerous cells, however, its poor solubility is restricted its application. To overcome this issue, this paper employed dendrosomal curcumin (DNC) was employed to in prevent hepatocarcinoma in both RNA and protein levels. Hepatocarcinoma cells, p53 wild-type HepG2 and p53 mutant Huh7, were treated with DNC and investigated for toxicity study using MTT assay. Cell cycle distribution and apoptosis were analyzed using Flow-cytometry and Annexin-V-FLUOS/PI staining. Real-time PCR and Western blot were employed to analyze p53, BAX, Bcl-2, p21 and Noxa in DNC-treated cells. DNC inhibited the growth in the form of time-dependent manner, while the carrier alone was not toxic to the cell. Flow-cytometry data showed the constant concentration of 20μM DNC during the time significantly increases cell population in SubG1 phase. Annexin-V-PI test showed curcumin-induced apoptosis was enhanced in Huh7 as well as HepG2, compared to untreated cells. Followed by treatment, mRNA expression of p21, BAX, and Noxa increased, while the expression of Bcl-2 decreased, and unlike HepG2, Huh7 showed down-regulation of p53. In summary, DNC-treated hepatocellular carcinoma cells undergo apoptosis by changing the expression of genes involved in the apoptosis and proliferation processes. These findings suggest that DNC, as a plant-originated therapeutic agent, could be applied in cancer treatment.
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Maryam
authors.initials: M
authors.lastname: Montazeri
authors.affiliation: Department of Genetics, School of Biological Sciences, Tarbiat Modares University, Tehran, Iran. Electronic address: Sadeghma@modares.ac.ir.
authors.forename: Majid
authors.initials: M
authors.lastname: Sadeghizadeh
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Yones
authors.initials: Y
authors.lastname: Pilehvar-Soltanahmadi
authors.affiliation: Imam Reza Teaching Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Faraz
authors.initials: F
authors.lastname: Zarghami
authors.affiliation: Department of Medical Genetic, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
authors.forename: Samaneh
authors.initials: S
authors.lastname: Khodi
authors.affiliation: Department of Molecular Biology and Biotechnology, University of Aix-Marseille, Marseille, France.
authors.forename: Mina
authors.initials: M
authors.lastname: Mohaghegh
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Sadeghzadeh
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran; Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address: zarghami@tbzmed.ac.ir.
authors.forename: Nosratollah
authors.initials: N
authors.lastname: Zarghami
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D016193:G1 Phase / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry*; D012333:RNA, Messenger / Q000378:metabolism; D012995:Solubility
chemical_list: D051017:Apoptosis Regulatory Proteins; D012333:RNA, Messenger; D003474:Curcumin
keywords: Apoptosis; Dendrosomal curcumin; Hepatocarcinoma; Real-time PCR; p53 mutant