title: Targeting Cancer Stem Cells for Chemoprevention of Pancreatic Cancer.
abstract: Pancreatic ductal adenocarcinoma is one of the deadliest cancers worldwide and the fourth leading cause of cancer-related deaths in United States. Regardless of the advances in molecular pathogenesis and consequential efforts to suppress the disease, this cancer remains a major health problem in United States. By 2030, the projection is that pancreatic cancer will be climb up to be the second leading cause of cancer-related deaths in the United States. Pancreatic cancer is a rapidly invasive and highly metastatic cancer, and does not respond to standard therapies. Emerging evidence supports that the presence of a unique population of cells called cancer stem cells (CSCs) as potential cancer inducing cells and efforts are underway to develop therapeutic strategies targeting these cells. CSCs are rare quiescent cells, and with the capacity to self-renew through asymmetric/symmetric cell division, as well as differentiate into various lineages of cells in the cancer. Studies have been shown that CSCs are highly resistant to standard therapy and also responsible for drug resistance, cancer recurrence and metastasis. To overcome this problem, we need novel preventive agents that target these CSCs. Natural compounds or phytochemicals have ability to target these CSCs and their signaling pathways. Therefore, in the present review article, we summarize our current understanding of pancreatic CSCs and their signaling pathways, and the phytochemicals that target these cells including curcumin, resveratrol, tea polyphenol EGCG (epigallocatechin- 3-gallate), crocetinic acid, sulforaphane, genistein, indole-3-carbinol, vitamin E δ- tocotrienol, Plumbagin, quercetin, triptolide, Licofelene and Quinomycin. These natural compounds or phytochemicals, which inhibit cancer stem cells may prove to be promising agents for the prevention and treatment of pancreatic cancers.
authors.affiliation: Department of Surgery, the University of Kansas Medical Center, Kansas City, KS 66160, United States.|The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Dharmalingam
authors.initials: D
authors.lastname: Subramaniam
authors.affiliation: Department of Surgery, the University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kaushik
authors.affiliation: Department of Surgery, the University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Prasad
authors.initials: P
authors.lastname: Dandawate
authors.affiliation: Department of Surgery, the University of Kansas Medical Center, Kansas City, KS 66160, United States.|The University of Kansas Cancer Center, The University of Kansas Medical Center, Kansas City, KS 66160, United States.
authors.forename: Shrikant
authors.initials: S
authors.lastname: Anant
mesh_terms: D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D000089742:Doublecortin-Like Kinases; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D064209:Phytochemicals / Q000494:pharmacology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D064209:Phytochemicals; D051153:Wnt Proteins; D002392:Catechin; C045651:epigallocatechin gallate; C117347:DCLK1 protein, human; D000089742:Doublecortin-Like Kinases; D017346:Protein Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases
keywords: Cancer stem cells; DCLK1; chemoprevention; natural compounds; pancreatic cancer; signaling.