title: Isolation, Characterization and Anticancer Potential of Cytotoxic Triterpenes from Betula utilis Bark.
abstract: Betula utilis, also known as Himalayan silver birch has been used as a traditional medicine for many health ailments like inflammatation, HIV, renal and bladder disorders as well as many cancers from ages. Here, we performed bio-guided fractionation of Betula utilis Bark (BUB), in which it was extracted in methanol and fractionated with hexane, ethyl acetate, chloroform, n-butanol and water. All six fractions were evaluated for their in-vitro anticancer activity in nine different cancer cell lines and ethyl acetate fraction was found to be one of the most potent fractions in terms of inducing cytotoxic activity against various cancer cell lines. By utilizing column chromatography, six triterpenes namely betulin, betulinic acid, lupeol, ursolic acid (UA), oleanolic acid and β-amyrin have been isolated from the ethyl acetate extract of BUB and structures of these compounds were unraveled by spectroscopic methods. β-amyrin and UA were isolated for the first time from Betula utilis. Isolated triterpenes were tested for in-vitro cytotoxic activity against six different cancer cell lines where UA was found to be selective for breast cancer cells over non-tumorigenic breast epithelial cells (MCF 10A). Tumor cell selective apoptotic action of UA was mainly attributed due to the activation of extrinsic apoptosis pathway via up regulation of DR4, DR5 and PARP cleavage in MCF-7 cells over non-tumorigenic MCF-10A cells. Moreover, UA mediated intracellular ROS generation and mitochondrial membrane potential disruption also play a key role for its anti cancer effect. UA also inhibits breast cancer migration. Altogether, we discovered novel source of UA having potent tumor cell specific cytotoxic property, indicating its therapeutic potential against breast cancer.
authors.affiliation: Phytochemistry Division, CSIR-National Botanical Research Institute, Lucknow, 226 001, India.
authors.forename: Tripti
authors.initials: T
authors.lastname: Mishra
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute (CDRI), Lucknow, 226031, India.
authors.forename: Rakesh Kumar
authors.initials: RK
authors.lastname: Arya
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute (CDRI), Lucknow, 226031, India.
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Meena
authors.affiliation: Department of chemistry, D.S.B. Campus Kumaun University, Nainital, 263002, India.
authors.forename: Pushpa
authors.initials: P
authors.lastname: Joshi
authors.affiliation: Phytochemistry Division, CSIR-National Botanical Research Institute, Lucknow, 226 001, India.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Pal
authors.affiliation: Plant Diversity, Systematics and Herbarium Division, CSIR-National Botanical Research Institute, Lucknow, 226001, India.
authors.forename: Baleshwar
authors.initials: B
authors.lastname: Meena
authors.affiliation: Plant Diversity, Systematics and Herbarium Division, CSIR-National Botanical Research Institute, Lucknow, 226001, India.
authors.forename: D K
authors.initials: DK
authors.lastname: Upreti
authors.affiliation: Plant Diversity, Systematics and Herbarium Division, CSIR-National Botanical Research Institute, Lucknow, 226001, India.
authors.forename: T S
authors.initials: TS
authors.lastname: Rana
authors.affiliation: Biochemistry Division, CSIR-Central Drug Research Institute (CDRI), Lucknow, 226031, India.
authors.forename: Dipak
authors.initials: D
authors.lastname: Datta
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D029662:Betula / Q000737:chemistry*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D024301:Plant Bark / Q000737:chemistry*; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D014315:Triterpenes; D000097245:Ursolic Acid