title: The plant-derived triterpenoid tingenin B is a potent anticancer agent due to its cytotoxic activity on cancer stem cells of breast cancer in vitro.
abstract: Despite the rapid advances in chemotherapy regimens, the outcome of patients with breast cancer is not satisfactory. One of the reasons of this dissatisfaction is that subsets of cells in tumors which referred as cancer stem cells (CSCs) show and/or gain resistance to therapies. Thus, compounds that target CSCs are urgently needed. Since some are already used in the clinic, natural products have great potential for further development as anti cancer drugs. The aim of this study is to investigate the cytotoxic activity of tingenin b (or 22β-hydroxytingenone) which is a quinone-methide triterpenoid structurally related to tingenone, against breast CSCs (stem-cell enriched population from MCF-7 cell line, MCF-7s). It has been found that tingenin b was cytotoxic against MCF-7s (IC50value for 48 h was found to be 2.38 μM) by inducing apoptosis. It was evident by Annexin V staining positivity, decreased mitochondrial membrane potential and Bcl-2 dephosphorylation with a concomitant increase in Bax protein expression. In addition, endoplasmic reticulum stress was also found to be involved in tingenin b-induced cell death. In conclusion, the results warrant further studies aimed at elucidating and corroborating its possible use in the treatment of breast cancer.
authors.affiliation: Uludag University, Faculty of Arts and Sciences, Department of Biology, Bursa, Turkey.
authors.forename: Buse
authors.initials: B
authors.lastname: Cevatemre
authors.affiliation: Department of Chemistry and Technology of Drugs, Sapienza University of Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Bruno
authors.initials: B
authors.lastname: Botta
authors.affiliation: Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, viale Regina Elena 291, 00161 Roma, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Chemistry and Technology of Drugs, Sapienza University of Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy; Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, viale Regina Elena 291, 00161 Roma, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Berardozzi
authors.affiliation: Department of Chemistry and Technology of Drugs, Sapienza University of Roma, Piazzale Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Ingallina
authors.affiliation: Uludag University, Faculty of Medicine, Department of Medical Biochemistry, Bursa, Turkey. Electronic address: eulukaya@uludag.edu.tr.
authors.forename: Engin
authors.initials: E
authors.lastname: Ulukaya
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000473:pathology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D029755:Maytenus / Q000737:chemistry*; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000473:pathology*; D008517:Phytotherapy; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D014315:Triterpenes; C066185:tingenin B
keywords: Breast; Chemotherapy; ER stress; Malignancy; Mammosphere; Tingenone