title: A novel compound RY10-4 downregulates P-glycoprotein expression and reverses multidrug-resistant phenotype in human breast cancer MCF-7/ADR cells.
abstract: P-glycoprotein (P-gp), an important efflux transporter, is encoded by the MDR1 class of genes and is a major element of the multidrug resistance (MDR) phenomenon in breast cancers. The most common approved cause of MDR in cancer tissues is the over-expression of P-gp. At present, a novel potent anti-tumor compound RY10-4 has been synthesized by our team, which has a similar structure close to protoapigenone. We chose MCF-7/ADR cells, an adriamycin (ADR) - selected human breast tumor cell line with the MDR phenotype, to study the anticancer features of this novel compound in our experiments. In cytotoxicity and apoptosis tests, it was shown that RY10-4 significantly inhibited cell growth, induced apoptosis, potentiated ADR cytotoxicity and restored chemotherapy sensitivity in the MDR cancer cells. Furthermore, our results suggested that RY10-4 reversed MDR partially by down-regulation of P-gp and MDR1 expressions in the MCF-7/ADR cell line. Besides, it is seen that RY10-4 could reduce the intracellular ATP level. Our studies give the theoretical basis for the possible clinical applications of RY10-4 alone or in combination with other chemotherapeutic drugs in the treatment of MDR tumors.
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China.
authors.forename: Pingping
authors.initials: P
authors.lastname: Xue
authors.affiliation: First Clinical School, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, PR China.
authors.forename: Xiaofan
authors.initials: X
authors.lastname: Yang
authors.affiliation: Synergy Innovation Center of Biological Peptide Antidiabetics of Hubei Province, School of Life Science, Wuchang University of Technology, Wuhan 430223, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China.
authors.forename: Chaomei
authors.initials: C
authors.lastname: Xiong
authors.affiliation: Key Laboratory of Natural Medicinal Chemistry and Resources Evaluation of Hubei Province, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, 13# Hangkong Road, Wuhan 430030, PR China. Electronic address: jinlan8152@163.com.
authors.forename: Jinlan
authors.initials: J
authors.lastname: Ruan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D018432:Drug Resistance, Multiple / Q000187:drug effects / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D010641:Phenotype; D011753:Pyrones / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: C574037:2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)pyran-4-one; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D011753:Pyrones; D004317:Doxorubicin
keywords: Multidrug-resistance (MDR); P-glycoprotein (P-gp); RY10-4; Reversal effect