title: The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma.
abstract: Multiple myeloma (MM) is an incurable plasma cell malignancy where nearly all patients succumb to a relapse. The current preclinical models of MM target the plasma cells, constituting the bulk of the tumor, leaving the cancer stem cells to trigger a relapse. Utilizing a three-dimensional tissue culture system where cells were grown in extracellular matrix designed to reconstruct human bone marrow, we tested the anti-multiple myeloma cancer stem cell (MM-CSC) potential of two natural product inhibitors of nuclear factor κB (NFκB). Here we show that parthenolide and andrographolide are potent anti-MM-CSC agents. Both natural products demonstrated preferential toxicity toward MM-CSCs over non-tumorigenic MM cells. Addition of the bone marrow stromal compartment abrogated andrographolide activity while having no effect on parthenolide cytoxicity. This is the first report of a natural product with anti-CSC activity in myeloma, suggesting that it has the potential to improve the survival of patients with MM by eliminating the relapse-causing MM-CSCs.
authors.affiliation: Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Gunn
authors.forename: John T
authors.initials: JT
authors.lastname: Williams
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Huynh
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Iannotti
authors.forename: Changho
authors.initials: C
authors.lastname: Han
authors.forename: Francis J
authors.initials: FJ
authors.lastname: Barrios
authors.forename: Stephen
authors.initials: S
authors.lastname: Kendall
authors.forename: Carlotta A
authors.initials: CA
authors.lastname: Glackin
authors.forename: David A
authors.initials: DA
authors.lastname: Colby
authors.forename: Julia
authors.initials: J
authors.lastname: Kirshner
mesh_terms: D035685:Andrographis / Q000737:chemistry; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015394:Molecular Structure; D009101:Multiple Myeloma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D012717:Sesquiterpenes / Q000737:chemistry / Q000494:pharmacology*; D020903:Tanacetum parthenium / Q000737:chemistry
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004224:Diterpenes; D016328:NF-kappa B; D010936:Plant Extracts; D012717:Sesquiterpenes; C002669:parthenolide; C030419:andrographolide