title: Selective anti-proliferation of HER2-positive breast cancer cells by anthocyanins identified by high-throughput screening.
abstract: Overexpressed Human epidermal growth factor receptor 2 (HER2) drives the biology of 20% breast cancer and is a prediction of a poor prognosis for patients. HER2-targeted therapies significantly improve outcomes for HER2-positive patients. Traditional Chinese herbs/medicines have been used to treat breast cancer patients including HER2-positive patients in Asia for decades. Although the traditional medicines demonstrate efficacy in clinics for HER2-positive patients, the mechanism is largely unknown. In this article, we screened a 10,000 natural product library in 6 different cell lines representing breast cancer, and assessed the ability of each drug to cause cytotoxicity through a high-throughput screening approach. We have identified eight natural compounds that selectively inhibit the proliferation of HER2-positive cells. Two of the hit compounds, peonidin-3-glucoside and cyaniding-3-glucoside, are both extracts from black rice. They inhibit the phospho-HER2 and phospho-AKT and were confirmed to induce HER2-psotive breast cancer cells apoptosis both in vitro and in vivo. Peonidin-3-glucoside and cyaniding-3-glucoside treatments significantly reduced the tumor size and volume in vivo compared to the control group. There is no significant difference of antitumorgenic effects between peonidin-3-glucoside and cyaniding-3-glucoside treatments.
authors: Department of Scientific Research, First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan Province, China.
authors: Weihua
authors: W
authors: Liu
authors: Jinmei
authors: J
authors: Xu
authors: Shaoping
authors: S
authors: Wu
authors: Yilun
authors: Y
authors: Liu
authors: Xiaoping
authors: X
authors: Yu
authors: Juan
authors: J
authors: Chen
authors: Xi
authors: X
authors: Tang
authors: Zhi
authors: Z
authors: Wang
authors: Xiaohu
authors: X
authors: Zhu
authors: Xin
authors: X
authors: Li
mesh_terms: D000818:Animals; D000872:Anthocyanins / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D057166:High-Throughput Screening Assays; D006801:Humans; D051379:Mice; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000872:Anthocyanins; D000970:Antineoplastic Agents; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human