title: Nexrutine inhibits survival and induces G1 cell cycle arrest, which is associated with apoptosis or autophagy depending on the breast cancer cell line.
abstract: Breast cancers that are estrogen receptor (ER) negative or are ER negative with ErbB2/HER-2 overexpression have a poor prognosis, which emphasizes the importance of developing compounds for preventing breast cancer. Nexrutine, an herbal extract from the plant Phellodendron amurense, has been used for centuries in Asian medicine to treat inflammation, gastroenteritis, abdominal pain, and diarrhea. In this study we investigated the anticancer effects of Nexrutine on ER negative breast cancer cell lines that are positive or negative for HER-2. Nexrutine decreased the activities of 2 potential targets of breast cancer, cyclooxygenase (COX)-2, and peroxisome proliferators activated receptor gamma (PPARγ). The antiinflammatory effects of Nexrutine were evident with decreased prostaglandin (PG)E2 production, protein expression of microsomal PGE2 synthase (mPGES), and PPARγ. Nexrutine decreased cell survival and induced a G1 cell cycle arrest in SkBr3 and MDA-MB 231 cells, which were associated with reduced protein expression of Cyclin D1 and cdk2 along with increased protein expression of p21 and p27. The growth-inhibitory effect of Nexrutine was associated with apoptosis in SkBr3 cells and autophagy in MDA-MB231 cells. Based on these findings, we propose that Nexrutine may provide a novel approach for protection against breast cancer.
authors.affiliation: a Department of Surgery , Thomas Jefferson University , Philadelphia , Pennsylvania , USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Yan
authors.forename: Susan
authors.initials: S
authors.lastname: Lanza-Jacoby
authors.forename: Chenguang
authors.initials: C
authors.lastname: Wang
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D028321:Plant Preparations / Q000737:chemistry; D000071876:Prostaglandin-E Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D015232:Dinoprostone; D019746:Intramolecular Oxidoreductases; D047495:PPAR gamma; D010936:Plant Extracts; D028321:Plant Preparations; D000071876:Prostaglandin-E Synthases; D018719:Erb-b2 Receptor Tyrosine Kinases; C512605:Nexrutine; C508053:ERBB2 protein, human