title: Growth inhibition of human liver carcinoma HepG2 cells and α-glucosidase inhibitory activity of Murdannia bracteata (C.B. Clarke) Kuntze ex J.K. Morton extracts.
abstract: BACKGROUND
  The juice of the entire fresh herb and infusion of dried sample of Murdannia bracteata are consumed to treat liver cancer and diabetes in Malaysia. However, no scientific evidence of these bioactivities has been reported.
  
  
  METHODS
  To verify the therapeutic potentials of sequential extracts and infusion of this plant by determining its cytotoxicity against human liver carcinoma HepG2 cells and α-glucosidase inhibitory activity. The cytotoxic activities of the extracts against HepG2 were determined using a methylene blue assay, and an α-glucosidase inhibitory assay was used to assess anti-diabetic activity. The molecular basis of the anti-hepatocellular carcinoma activity of the most active extract was determined using RT-PCR. Chemical profiling of the most active extract was performed using GC-MS and UPLC analyses.
  
  
  RESULTS
  The results obtained from the cytotoxic screening revealed the dose-dependent growth inhibition of the HepG2 cells by only the hexane extract, with an EC50 value of 37.17±1.00 µg/ml. The HepG2 cell death was found to be apoptotic in nature and based on the significant biphasic induction of caspase-3, suggesting that the extract inhibited cell growth through a caspase-3-dependent pathway. The hexane extract also displayed α-glucosidase inhibitory activity, with an EC50 of 117.04±2.34 µg/ml. GC-MS analysis revealed that α-tocopherol was the major volatile compound in the hexane extract, and two phenolics (apigenin and caffeic acid derivatives) were detected using UPLC.
  
  
  CONCLUSIONS
  Based on various published reports, it could be suggested that α-tocopherol and apigenin derivatives might be involved in the apoptosis-based cytotoxicity of the active extract of this plant against HepG2 carcinoma cells. The effects of this plant in the treatment of diabetes can be related to the presence of α-glucosidase inhibitors, such as the caffeic acid derivative identified in the active extract.
authors.affiliation: School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Kheng Leong
authors.initials: KL
authors.lastname: Ooi
authors.affiliation: School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
authors.forename: Suh In
authors.initials: SI
authors.lastname: Loh
authors.affiliation: Advanced Medical & Dental Institute, Universiti Sains Malaysia, Bertam, 13200 Kepala Batas, Penang, Malaysia.
authors.forename: Mei Lan
authors.initials: ML
authors.lastname: Tan
authors.affiliation: Institute of Marine Biotechnology, Universiti Malaysia Terengganu, 21030 Kuala Terengganu, Terengganu, Malaysia.
authors.forename: Tengku Sifzizul Tengku
authors.initials: TS
authors.lastname: Muhammad
authors.affiliation: School of Biological Sciences, Universiti Sains Malaysia, 11800 USM, Penang, Malaysia. Electronic address: shaida@usm.my.
authors.forename: Shaida Fariza
authors.initials: SF
authors.lastname: Sulaiman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000201:enzymology; D053148:Caspase 3 / Q000378:metabolism; D065089:Glycoside Hydrolase Inhibitors / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000201:enzymology; D019684:Magnoliopsida; D010936:Plant Extracts / Q000494:pharmacology*; D000520:alpha-Glucosidases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D065089:Glycoside Hydrolase Inhibitors; D010936:Plant Extracts; D000520:alpha-Glucosidases; D053148:Caspase 3
keywords: Apigenin derivative; Caspase-3; HepG2; Murdannia bracteata; α-Glucosidase inhibitory activity; α-Tocopherol