title: Novel molecular, cytotoxical, and immunological study on promising and selective anticancer activity of mung bean sprouts.
abstract: BACKGROUND
  The anticancer and immunomodulatory activity of mung bean sprouts (MBS) and the underlying mechanisms against human cervical and hepatocarcinoma cancer cells were explored.
  
  
  METHODS
  MBS cytotoxicity and MBS-induced anticancer cytokines, TNF-α and IFN-β from cancer cells, and immunological cytokines, IL-4, IFN-γ, and IL-10 from peripheral mononuclear cells (PMNC) were assessed by MTS and ELISA assays. Apoptotic cells were investigated by flow cytometry. The expression level of apoptotic genes (Bax, BCL-2, Capsases 7-9) and cell cycle regulatory genes (cyclin D, E, and A) and tumor suppressor proteins (p27, p21, and p53) was assessed by real-time qPCR in the cancer cells treated with extract IC50.
  
  
  RESULTS
  The cytotoxicity on normal human cells was significantly different from HeLa and HepG2 cells, 163.97 ± 5.73, 13.3 ± 0.89, and 14.04 ± 1.5 mg/ml, respectively. The selectivity index (SI) was 12.44 ± 0.83 for HeLa and 11.94 ± 1.2 for HepG2 cells. Increased levels of TNF-α and IFN-β were observed in the treated HeLa and HepG2 culture supernatants when compared with untreated cells. MBS extract was shown to be an immunopolarizing agent by inducing IFNγ and inhibiting IL-4 production by PBMC; this leads to triggering of CMI and cellular cytotoxicity. The extract induced apoptosis, in a dose and time dependent manner, in treated HeLa and HepG2, but not in untreated, cells (P < 0.05). The treatment significantly induced cell cycle arrest in G0/G1 in HeLa cells. The percentage of cells in G0/G1 phase of the treated HeLa cells increased from 62.87 ± 2.1%, in untreated cells, to 80.48 ± 2.97%. Interestingly, MBS IC50 induced the expression of apoptosis and tumor suppressor related genes in both HeLa and HepG2 cells. MBS extract succeeded in inducing cdk-inhibitors, p21, p53, and p27 in HeLa cells while it induced only p53 in HepG2 cells (P < 0.05). This is a clue for the cell type- specific interaction of the studied extract. These proteins inhibit the cyclin-cdk complexes apart from the presence of some other components that might stimulate some cyclins such as cyclin E, A, and D.
  
  
  CONCLUSIONS
  MBS extract was shown to be a potent anticancer agent granting new prospects of anticancer therapy using natural products.
authors.affiliation: Department of Microbiology, College of Medicine, Baghdad University, Baghdad, Iraq.
authors.forename: Rand R
authors.initials: RR
authors.lastname: Hafidh
authors.forename: Ahmed S
authors.initials: AS
authors.lastname: Abdulamir
authors.forename: Fatimah Abu
authors.initials: FA
authors.lastname: Bakar
authors.forename: Farid Azizi
authors.initials: FA
authors.lastname: Jalilian
authors.forename: Faridah
authors.initials: F
authors.lastname: Abas
authors.forename: Zamberi
authors.initials: Z
authors.lastname: Sekawi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000235:genetics; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000235:genetics / Q000378:metabolism; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000037:antagonists & inhibitors; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007887:Fabaceae; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012639:Seeds; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D016213:Cyclins; D016207:Cytokines; D007155:Immunologic Factors; D010936:Plant Extracts; D025521:Tumor Suppressor Proteins; D018844:Cyclin-Dependent Kinases