title: Self assembled nano fibers of betulinic acid: A selective inducer for ROS/TNF-alpha pathway mediated leukemic cell death.
abstract: The main complication in betulinic acid (BA) based drug delivery has been observed due to its bulk structure. The present study demonstrates the potential effects of self assembled nano size betulinic acid (SA-BA) by treating human leukemic cell lines (KG-1A and K562) and its normal counterpart. Self assembly property of BA was investigated using SEM and DLS study which showed that the BA forms fibrous structure having few nanometers in diameter. Selective anti-leukemic efficacy study of SA-BA was investigated by cell viability assay. Mode of leukemic cell death and probable pathway of apoptosis was monitored by measuring ROS level, pro and anti-inflammatory cytokine status and expression of caspase-8 and caspage-3 by immunocytochemistry. Higher efficacy of SA-BA over non-assemble BA was monitored toward cancer cells, with no relevant toxicity to normal blood cells. SA-BA facilitated reactive oxygen species (ROS) mediated leukemic cell death, confirmed by pre-treatment of N-acetyl-L-cysteine. Induction of apoptosis by SA-BA treatment increased pro-inflammatory cytokines, specifically potentiated TNF-α mediated cell death, confirmed by expression of caspase-8 and caspage-3 by immunocytochemistry. This study explored the better anti-leukemic efficacy of SA-BA over BA and this modification will enrich the use of BA in cancer therapy.
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 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: Medicinal Chemistry and Immunology Laboratory, Department of Biotechnology, School of Chemical and Biotechnology, SASTRA University, Thanjavur 613 401, Tamil Nadu, India.
authors.forename: Santanu Kar
authors.initials: SK
authors.lastname: Mahapatra
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 Life Science and Biotechnology, Jadavpur University, Kolkata, India.
authors.forename: Parimal
authors.initials: P
authors.lastname: Karmakar
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: D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020014:K562 Cells; D007938:Leukemia / Q000473:pathology*; D015394:Molecular Structure; D057139:Nanofibers / Q000737:chemistry*; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D000094062:Betulinic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000094062:Betulinic Acid
keywords: Betulinic acid; Mitochondrial membrane potential; Reactive oxygen species; Self assembled; TNF-α