title: Abrus precatorius agglutinin-derived peptides induce ROS-dependent mitochondrial apoptosis through JNK and Akt/P38/P53 pathways in HeLa cells.
abstract: 10kDAGP, a tryptic digest of Abrus precatorius lectin 'Agglutinin' is known to induce apoptosis by mitochondria-dependent pathways in human cervical cancer (HeLa) cells. The present study was focused on deciphering the detailed molecular mechanism of apoptosis induction in vitro by 10kDAGP and also its in vivo therapeutic efficacy. For in vivo model, HeLa cell encapsulated hollow fiber was implanted in Swiss Albino mice and treated with 10kDAGP. Our results showed that 10kDAGP was able to enter the cell within a span of 20min and co-localized with mitochondria after 90min. of incubation. A drastic loss of mitochondrial membrane potential was noted within 6h of 10kDAGP administration along with an increase in ROS generation. ROS further led to symptoms of early apoptosis by deregulating Akt (Protein Kinase B) and activating c-Jun N-terminal Kinase (JNK), p38 Mitogen Activated Protein Kinase (MAPK), p53, and autophagy starting from ∼8h of incubation. Besides in vitro conditions, 10kDAGP activated JNK to mediate cancer cell killing in vivo. Therefore, 10kDAGP can be an excellent therapeutic agent as it can act through different ways in the cellular system. Future studies are directed to screen out active peptides from the pool of peptides and to study whether the mode of action is in synergistic way or in individual forms.
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Birendra
authors.initials: B
authors.lastname: Behera
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Debasish
authors.initials: D
authors.lastname: Mishra
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Bibhas
authors.initials: B
authors.lastname: Roy
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: K Sanjana P
authors.initials: KS
authors.lastname: Devi
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Rajan
authors.initials: R
authors.lastname: Narayan
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Joyjyoti
authors.initials: J
authors.lastname: Das
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Sudip K
authors.initials: SK
authors.lastname: Ghosh
authors.affiliation: Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India. Electronic address: tkmaiti@hijli.iitkgp.ernet.in.
authors.forename: Tapas K
authors.initials: TK
authors.lastname: Maiti
mesh_terms: D029912:Abrus; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001343:Autophagy / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D037121:Plant Lectins / Q000737:chemistry / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010455:Peptides; D037121:Plant Lectins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C016940:abrus agglutinin; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Abrus agglutinin derived peptides; Apoptosis and autophagy; Hollow fiber assay; JNK; ROS; p38