Person:
YILMAZ GÖLER, AYŞE MİNE

Profile Picture

Email Address

Birth Date

Research Projects

Organizational Units

OrgUnit Logo
Organizational Unit

Job Title

Last Name

YILMAZ GÖLER

First Name

AYŞE MİNE

Name

Filters

20222
Reset filters

Settings

Has files: true × Subject: Drug Guides ×

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    PublicationOpen Access
    Exploring the anticancer effects of brominated plastoquinone analogs with promising cytotoxic activity in MCF-7 breast cancer cells via cell cycle arrest and oxidative stress induction
    (2022-06-01) YILMAZ GÖLER, AYŞE MİNE; YILMAZ, BETÜL; Jannuzzı A. T., Yılmaz Göler A. M., Bayrak N., Yıldız M., Yıldırım H., Yılmaz B., Shilkar D., Jayaprakash Venkatesan R., Jayaprakash V., Tuyun A. F.
    Plastoquinone analogs are privileged structures among the known antiproliferative natural product-based compound families. Exploiting one of these analogs as a lead structure, we report the investigation of the brominated PQ analogs (BrPQ) in collaboration with the National Cancer Institute of Bethesda within the Developmental Therapeutics Program (DTP). These analogs exhibited growth inhibition in the micromolar range across leukemia, non-small cell lung cancer (EKVX, HOP-92, and NCI-H522), colon cancer (HCT-116, HOP-92), melanoma (LOX IMVI), and ovarian cancer (OVCAR-4) cell lines. One brominated PQ analog (BrPQ5) was selected for a full panel five-dose in vitro assay by the NCI’s Development Therapeutic Program (DTP) division to determine GI50, TGI, and LC50parameters. The brominated PQ analog (BrPQ5) displayed remarkable activity against most tested cell lines, with GI50values ranging from 1.55 to 4.41 µM. The designed molecules (BrPQ analogs) obeyed drug-likeness rules, displayed a favorable predictive Absorption, Distribution, Metabolism, and Excretion (ADME) profile, and an in silico simulation predicted a possibleBrPQ5interaction with proteasome catalytic subunits. Furthermore, the in vitro cytotoxic activity ofBrPQ5was assessed, and IC50values for U-251 glioma, MCF-7 and MDA-MB-231 breast cancers, DU145 prostate cancer, HCT-116 colon cancer, and VHF93 fibroblast cell lines were evaluated using an MTT assay. MCF-7 was the most affected cell line, and the effects ofBrPQ5on cell proliferation, cell cycle, oxidative stress, apoptosis/necrosis induction, and proteasome activity were further investigated in MCF-7 cells. The in vitro assay results showed thatBrPQ5caused cytotoxicity in MCF-7 breast cancer cells via cell cycle arrest and oxidative stress induction. However,BrPQ5did not inhibit the catalytic activity of the proteasome. These results provide valuable insights for further discovery of novel antiproliferative agents.
  • Thumbnail Image
    PublicationOpen Access
    Ubiquitin proteasomal system is a potential target of the toxic effects of organophosphorus flame retardant triphenyl phosphate
    (2022-11-01) YILMAZ GÖLER, AYŞE MİNE; Jannuzzı A. T. , Yılmaz Göler A. M. , Alpertunga B.
    © 2022 Elsevier B.V.The consumption of the widely used flame retardant Triphenyl phosphate (TPP) is increasing. It is now frequently detected in the environment and also domestically. Although the possibility of dermal exposure to TPP is quite high, little is known about its potential molecular toxicity mechanisms. In this study, we found that TPP caused cytotoxicity on human skin keratinocytes (HaCaT) and significantly inhibited the proliferation and cell migration in a concentration-dependent manner. Additionally, HaCaT cells were sensitive to TPP-induced apoptosis. Reactive oxygen species production was induced with TPP, which increased the protein carbonylation and lipid peroxidation levels. Moreover, TPP inhibited proteasome activity and increased the accumulation of ubiquitinated proteins. Exposure to TPP significantly increased the HSP90, HSP70, GRP94 and GRP78 protein levels. Overall, our findings indicate that TPP may pose a risk to human health and contribute to the current understanding of the risks of TPP at the molecular level.