title: Self-assembled betulinic acid protects doxorubicin induced apoptosis followed by reduction of ROS-TNF-α-caspase-3 activity.
abstract: Doxorubicin (DOX) is a well-known drug used to treat a wide range of solid tumor and hematological malignancies, but the use of this drug is now restricted owing to its severe side effects, including normal cellular toxicity. This study was conducted to evaluate the potency of self-assembled betulinic acid (SA-BA) against DOX induced chemotherapeutic toxicity in human peripheral blood lymphocytes (PBLs). The isolated betulinic acid from the bark of Ziziphus jujuba tree was purified by column chromatography and characterized by FT-IR, XRD, (1)H NMR and self-assembly property was investigated by SEM imaging. DOX treatment produced significant reduction of viability of PBLs mainly by lowering cellular anti-oxidant pool and elevating the reactive oxygen species level. Pre-treatment with SA-BA followed by DOX exposure for 24h protected the PBLs from DOX induced oxidative stress. Potent anti-apoptotic role of SA-BA was also confirmed by FACS analysis and western blot assay. Severe inflammation is one of the major concerns in DOX treatment. We found that pre-treatment with SA-BA on PBLs significantly protected the PBLs from DOX induced inflammation. Thus, our finding confirms that SA-BA can be used to ameliorate the cytotoxic effects of DOX, which can be a helpful strategy during DOX mediated chemotherapy in cancer patients.
authors.affiliation: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors.forename: Sandeep Kumar
authors.initials: SK
authors.lastname: Dash
authors.affiliation: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors.forename: Sourav
authors.initials: S
authors.lastname: Chattopadhyay
authors.affiliation: Department of Chemistry, University of Calcutta, 92, APC Road, Kolkata 700 009, India.
authors.forename: Totan
authors.initials: T
authors.lastname: Ghosh
authors.affiliation: Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors.forename: Shib Shankar
authors.initials: SS
authors.lastname: Dash
authors.affiliation: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors.forename: Satyajit
authors.initials: S
authors.lastname: Tripathy
authors.affiliation: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors.forename: Balaram
authors.initials: B
authors.lastname: Das
authors.affiliation: Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore 721 102, West Bengal, India.
authors.forename: Braja Gopal
authors.initials: BG
authors.lastname: Bag
authors.affiliation: Department of Chemistry, University of Calcutta, 92, APC Road, Kolkata 700 009, India.
authors.forename: Debasis
authors.initials: D
authors.lastname: Das
authors.affiliation: Immunology and Microbiology Laboratory, Department of Human Physiology with Community Health, Vidyasagar University, Midnapore 721 102, West Bengal, India. Electronic address: sroy.vu@hotmail.com.
authors.forename: Somenath
authors.initials: S
authors.lastname: Roy
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism*; D053144:Cell Nucleus Shape / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D019803:Glutathione Disulfide / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008855:Microscopy, Electron, Scanning; D055620:Optical Phenomena; D018384:Oxidative Stress / Q000187:drug effects; D053978:Pentacyclic Triterpenes; D020011:Protective Agents / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D014961:X-Ray Diffraction; D000094062:Betulinic Acid
chemical_list: D018836:Inflammation Mediators; D053978:Pentacyclic Triterpenes; D020011:Protective Agents; D017382:Reactive Oxygen Species; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D007770:L-Lactate Dehydrogenase; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D019803:Glutathione Disulfide; D000094062:Betulinic Acid
keywords: Apoptosis; Cytotoxicity; DOX; Protective role; Reactive oxygen species; Self-assembled betulinic acid