Nexrutine Inhibits Survival and Induces G1 Cell Cycle Arrest, Which Is Associated with Apoptosis or Autophagy Depending on the Breast Cancer Cell Line

• Published in: Nutrition and cancer Vol. 66; no. 3; pp. 506 - 516
• Main Authors: Yan, Guang, Lanza-Jacoby, Susan, Wang, Chenguang
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis Group 03.04.2014; Taylor & Francis Ltd
• Subjects: Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Cell cycle; Cell Line, Tumor - drug effects; Cell Survival - drug effects; Dinoprostone - metabolism; Estrogens; Female; Flowers & plants; G1 Phase Cell Cycle Checkpoints - drug effects; Humans; Intramolecular Oxidoreductases - metabolism; Plant Extracts - pharmacology; Plant Preparations - chemistry; PPAR gamma - genetics; PPAR gamma - metabolism; Prostaglandin-E Synthases; Receptor, ErbB-2 - metabolism; Triple Negative Breast Neoplasms - drug therapy; Triple Negative Breast Neoplasms - pathology
• ISSN: 0163-5581; 1532-7914
• DOI: 10.1080/01635581.2013.780627

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)E 2 production, protein expression of microsomal PGE 2 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.