DOI: 10.5061/dryad.dbrv15f7s
title: Data from: A novel triptolide analog downregulates NF-kB and induces mitochondrial apoptosis pathways in human pancreatic cancer

description: Pancreatic cancer is the seventh leading cause of cancer-related death
 worldwide, and despite advancements in disease management, the 5-year
 survival rate stands at only 12%. Triptolides have potent anti-tumor
 activity against different types of cancers, including pancreatic cancer,
 however poor solubility and toxicity limit their translation into clinical
 use. We synthesized a novel pro-drug of triptolide,
 (E)-19-[(1'-benzoyloxy-1'-phenyl)-methylidene]-Triptolide
 (CK21), which was formulated into an emulsion for in vitro and in vivo
 testing in rats and mice, and using human pancreatic cancer cell lines and
 patient-derived pancreatic tumor organoids. A time-course transcriptomic
 profiling of tumor organoids treated with CK21 in vitro was conducted to
 define its mechanism of action, as well as transcriptomic profiling at a
 single time point post-CK21 administration in vivo. Intravenous
 administration of emulsified CK21 resulted in the stable release of
 triptolide, and potent anti-proliferative effects on human pancreatic
 cancer cell lines and patient-derived pancreatic tumor organoids in vitro,
 and with minimal toxicity in vivo. Time course transcriptomic profiling of
 tumor organoids treated with CK21 in vitro revealed &lt;10
 differentially expressed genes (DEGs) at 3 h and ~8,000 DEGs at 12 h.
 Overall inhibition of general RNA transcription was observed, and
 Ingenuity pathway analysis together with functional cellular assays
 confirmed inhibition of the NF-κB pathway, increased oxidative
 phosphorylation and mitochondrial dysfunction, leading ultimately to
 increased reactive oxygen species (ROS) production, reduced
 B-cell-lymphoma protein 2 (BCL2) expression, and mitochondrial-mediated
 tumor cell apoptosis. CK21 is a novel pro-drug of triptolide that exerts
 potent anti-proliferative effects on human pancreatic tumors by inhibiting
 the NF-κB pathway, leading ultimately to mitochondrial-mediated tumor cell
 apoptosis.
description: # A novel triptolide analog downregulates NF-kB and induces mitochondrial
 apoptosis pathways in human pancreatic cancer
 ## Description of the data
 and file structure These are summary of original data for CK21
 pharmacokinetic in rats: detection of CK21 and Triptolide in male and
 female rats after IV injection (SD: standard deviation; ND: not detected;
 CV: coefficient of variation; BQL: below quantification limit) CK21
 viability assay with different cancer cell lines Bioluminescence intensity
 of each mice bearing luciferase transfected AsPC-1 orthotopic tumors under
 28 days treatment of CK21 (FD: found dead). CK21 efficacy study on AsPC-1
 and Panc-1 subcutaneous tumors (SEM: standard error). * Size for AsPC-1
 tumors and mice weight under different dosages for CK21 * Size for Panc-1
 tumors and mice weight under 3 mg/kg dosage for CK21 CK21 efficacy study
 on AsPC-1 subcutaneous tumor with different treatment plans (SEM: standard
 error). * Combo therapy * Resue therapy * Delay therapy CK21 toxicity
 study on patient derived organoids and efficacy study on organoids
 implanted in nude mice (SEM: standard error). * In vitro toxicity with
 different CK21 concentration * In vivo efficacy Raw read counts for genes
 that differentially expressed in patient derived organoids after CK21
 treatment and in AsPC-1 orthotopic tumors after CK21 treatment. * U049 12
 hrs of treatment * U123 12 hrs of treatment * AsPC-1 3 days of treatment
 in vivo CK21 immunosuppression study using KPC cell lines in
 immunocompetent mice (SEM: standard error). * Mice with KPC960 tumors
 treated with or without CK21 * Specific killing assay of mice splenocytes
 and target cells p65 translocation of AsPC-1 and Panc-1 after CK21
 treatment. * p65 similarity * p65 density * p65 intensity