title: Curcumin and its analogues (PGV-0 and PGV-1) enhance sensitivity of resistant MCF-7 cells to doxorubicin through inhibition of HER2 and NF-kB activation.
abstract: Chemoresistance of breast cancer to doxorubicin is mediated mainly through activation of NF-kB and over expression of HER2. Curcumin and its analogues (PGV-0 and PGV-1) exert cytotoxic effects on T47D breast cancer cells. Suppression of NF-kB activation is suggested to contribute to this activity. The present study aimed to explore the effects of curcumin, PGV-0, and PGV-1 singly and in combination with doxorubicin on MCF-7/Dox cells featuring over-expression of HER2. In MTT assays, curcumin, PGV-0, and PGV-1 showed cytotoxicity effects against MCF-7/Dox with IC50 values of 80 μM, 21 μM, and 82 μM respectively. These compounds increased MCF-7/Dox sensitivity to doxorubicin. Cell cycle distribution analysis exhibited that the combination of curcumin and its analogues with Dox increased sub G-1 cell populations. Curcumin and PGV-1 but not PGV-0 decreased localization of p65 into the nucleus induced by Dox, indicating that activation of NF- kB was inhibited. Molecular docking of curcumin, PGV-0, and PGV-1 demonstrated high affinity to HER2 at ATP binding site. This interaction were directly comparable with those of ATP and lapatinib. These findings suggested that curcumin, PGV-0 and PGV-1 enhance the Dox cytotoxicity to MCF-7 cells through inhibition of HER2 activity and NF-kB activation.
authors: Cancer Chemoprevention Research Center, Faculty of Pharmacy, Universitas Gadjah Mada, Jalan Sekip Utara Yogyakarta, Japan E-mail : meiyan_e@ugm.ac.id.
authors: Edy
authors: E
authors: Meiyanto
authors: Dyaningtyas Dewi Pamungkas
authors: DD
authors: Putri
authors: Ratna Asmah
authors: RA
authors: Susidarti
authors: Retno
authors: R
authors: Murwanti
authors: Sardjiman
authors: Aditya
authors: A
authors: Fitriasari
authors: Ulfatul
authors: U
authors: Husnaa
authors: Hari
authors: H
authors: Purnomo
authors: Masashi
authors: M
authors: Kawaichi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D061986:MCF-7 Cells; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D003474:Curcumin; D004317:Doxorubicin; D016328:NF-kappa B; D018719:Erb-b2 Receptor Tyrosine Kinases; D051996:Transcription Factor RelA; C000592887:2- ((4-hydroxy-3,5-dimethylphenyl)methylidene)-5-((3-methoxy-4,5-dimethylphenyl)methylidene)cyclopentan-1-one; C587071:pentagamavunon-0