title: Phellinus linteus extract induces autophagy and synergizes with 5-fluorouracil to inhibit breast cancer cell growth.
abstract: Phellinus linteus (PL) is a medicinal mushroom due to its several biological properties, including anticancer activity. However, the mechanisms of its anticancer effect remain to be elucidated. We evaluated the inhibitory effects of the ethanolic extract from the PL combined with 5-FU on MDA-MB-231 breast cancer cell line and to determine the mechanism of cell death. Individually, PL extract and 5-FU significantly inhibited the proliferation of MDA-MB-231 cells in a dose-dependent manner. PL extract (30 mg/mL) in combination with 5-FU (10 μg/mL) synergistically inhibited MDA-MB-231 cells by 1.8-fold. PL did not induce apoptosis, as demonstrated by the DNA fragmentation assay, the sub-G1 population, and staining with annexin V-FITC and propidium iodide. The exposure of MDA-MB-231 cells to PL extracts resulted in several confirmed characteristics of autophagy, including the appearance of autophagic vacuoles revealed by monodansylcadaverine staining, the formation of acidic vesicular organelles, autophagosome membrane association of microtubule-associated protein light chain 3 (LC3) characterized by cleavage of LC3 and its punctuate redistribution, and ultrastructural observation of autophagic vacuoles by transmission electron microscopy. We concluded that PL extracts synergized with low doses of 5-FU to inhibit triple-negative breast cancer cell growth and demonstrated that PL extract can induce autophagy-related cell death.
authors.affiliation: a Department of Pathology , Chi Mei Medical Center , Tainan , Taiwan ; Department of Pathology, College of Medicine , Taipei Medical University , Taipei , Taiwan ; and Department of Medical Laboratory Science and Biotechnology , Chung Hwa University of Medical Technology , Tainan , Taiwan.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Lee
authors.forename: Keng-Fu
authors.initials: KF
authors.lastname: Hsu
authors.forename: Tai-An
authors.initials: TA
authors.lastname: Chiang
authors.forename: Chee-Jen
authors.initials: CJ
authors.lastname: Chen
mesh_terms: D000363:Agaricales / Q000737:chemistry; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004357:Drug Synergism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000187:drug effects; D000084682:Phellinus; D010936:Plant Extracts; D011134:Polysaccharides / Q000494:pharmacology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D008869:Microtubule-Associated Proteins; C526145:Phellinus linteus extract; D010936:Plant Extracts; D011134:Polysaccharides; D005472:Fluorouracil