title: Caspase mediated synergistic effect of Boswellia serrata extract in combination with doxorubicin against human hepatocellular carcinoma.
abstract: The study investigated the growth-inhibiting and apoptosis mediating effects of B. serrata extract as monotherapy and combination therapy with DOX against hepatocellular carcinoma cell lines. Boswellic acid rich fraction of B. serrata extract was prepared. MTT assay on HepG2 and Hep3B cells was carried out using B. serrata alone and in combination with DOX. Further, caspase-3 activity, TNF-α level, and IL-6 level were estimated. Isobolographic analysis was carried out to evaluate the effect of combination therapy. Additionally, protective effect of B. serrata extract on DOX induced hepatic toxicity was also evaluated in Wistar rats. B. serrata extract inhibited growth of HepG2 (IC50 value of 21.21 ± 0.92 μg/mL) as well as HepG2 (IC50 value of 18.65 ± 0.71 μg/mL). DOX inhibited growth in HepG2 and Hep3B cells with an IC50 of 1.06 ± 0.04 μg/mL and 1.92 ± 0.09 μg/mL. Isobolographic analysis showed combination index (CI) of DOX and B. serrata extract of 0.53 ± 0.03 to 0.79 ± 0.02 suggesting synergistic behavior against the two cell lines. B. serrata extract also caused dose dependent increase in caspase-3 activity, TNF-α level, and IL-6 level which was higher (P < 0.001) with DOX (1 μM) and B. serrata extract (20 μg/mL) combination. B. serrata extract also protected Wistar rats against DOX induced hepatic toxicity.
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Mohammad Ahmed
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department of Pharmacognosy & Phytochemistry, Faculty of Pharmacy, Hamdard University (Jamia Hamdard), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Mhaveer
authors.initials: M
authors.lastname: Singh
authors.affiliation: Department of Pharmacognosy & Phytochemistry, Faculty of Pharmacy, Hamdard University (Jamia Hamdard), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Masood Shah
authors.initials: MS
authors.lastname: Khan
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi 110062, India.
authors.forename: Abul Kalam
authors.initials: AK
authors.lastname: Najmi
authors.affiliation: Department of Pharmacognosy & Phytochemistry, Faculty of Pharmacy, Hamdard University (Jamia Hamdard), Hamdard Nagar, New Delhi 110062, India.
authors.forename: Sayeed
authors.identifier: 0000-0003-1573-152X
authors.initials: S
authors.lastname: Ahmad
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D029743:Boswellia / Q000737:chemistry*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D010936:Plant Extracts / Q000008:administration & dosage; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D004317:Doxorubicin; D053148:Caspase 3