title: Enhancement of the cytotoxic effects of Cytarabine in synergism with Hesperidine and Silibinin in Acute Myeloid Leukemia: An in-vitro approach.
abstract: OBJECTIVE
  Acute Myeloid Leukemia (AML) therapy continues to be a daunting challenge. Cytosine Arabinoside (Ara-C) is widely used to treat hematological malignancy in humans, but often becomes ineffective because of increased resistance to the drug which may lead to a worse prognosis. Therefore new strategies are needed to understand the mechanism responsible for drug resistance and to develop new therapies to overcome it. Research evidence based on natural compounds used alone or in combination with current chemotherapeutic agents proved their efficacy to treat and prevent cancer. Hesperidin and Silibinin displayed anti-cancer activity against various types of cancers and cell lines and can be used in combination with Cytarabine with the aim to increase cytotoxicy profile and reduction in drug resistance. Experimental Work: Primary cells obtained from AML patient's bone marrow were used to develop in-vitro model and further exposed to various concentration of Cytarabine (10 nM-5000 nM), Hesperidin (0.5 μM-100 μM) and Silibinin (0.5 μM-100 μM) alone and in combination with Cytarabine (Hesperidin-25 μM, Silibinin10 μM) to check cytotoxicity using MTT assay. Synergistic effect was evaluated by Combination Index method.
  
  
  CONCLUSIONS
  In-vitro study of Hesperidin and Silibinin indicated their cytotoxicity at IC 50 value 50.12 μM and 16.2 μM, respectively. Combination Index study revealed Hesperidin and Silibinin both showed synergistic potential and decreased the IC 50 value of Cytarabine by ~5.9 and ~4.5 folds, respectively. Both natural compounds showed potential anti-leukemic activity hence may be used for AML therapy alone or in combination with other chemotherapeutic agents.
authors.forename: Urja N
authors.initials: UN
authors.lastname: Desai
authors.forename: Krupa P
authors.initials: KP
authors.lastname: Shah
authors.forename: Sheefa H
authors.initials: SH
authors.lastname: Mirza
authors.forename: Darshil K
authors.initials: DK
authors.lastname: Panchal
authors.forename: Sonia K
authors.initials: SK
authors.lastname: Parikh
authors.affiliation: Departments of Cancer Biology and Medical Oncology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India.
authors.forename: Rakesh M
authors.initials: RM
authors.lastname: Rawal
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001853:Bone Marrow / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D004357:Drug Synergism; D006569:Hesperidin / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy*; D000077385:Silybin; D012838:Silymarin / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D012838:Silymarin; D003561:Cytarabine; D000077385:Silybin; D006569:Hesperidin