Chemosensitivity of BRCA1-Mutated Ovarian Cancer Cells and Established Cytotoxic Agents

Haaften, Caroline van; Eendenburg, Jaap van; Boot, Arnoud; Corver, Willem E.; Haans, Lucien; Wezel, Tom van; Trimbos, J. Baptist

doi:10.1097/igc.0000000000001052

Cited by 3 publications

(3 citation statements)

References 27 publications

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“…In order to access the desired EPD (11), the trans-con guration in lactone (7) had to be transformed into a cis con guration. To that end, lactone (7) was converted into bromolactone (8) via deprotonation with LDA and bromination with carbon tetrabromide.…”

Section: Epd Synthesismentioning

confidence: 99%

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Synthesis of EPD, an established cytotoxic agent for ovarian cancer cells, and its efficacy in cisplatin and paclitaxel resistant tumor cells

Haaften,

Koek,

Eendenburg

et al. 2023

Preprint

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Ovarian cancer remains still the leading cause of death of gynaecological malignancy, for the greater part caused by tumour resistance to conventional treatment with cisplatin and paclitaxel. In the past a new compound, EPD, from the plant Calomeria amaranthoides has been isolated and proved to be a potential anti-cancer agent. The sesquiterpene lactone, EPD, or Eremophila-1(10)-11(13)-dien-12,8β-olide, has an alpha-methylene gamma-lactone ring, essential for its apoptotic activity. In order to have sufficient EPD material for further anti-tumour studies, a synthetic route has been developed. Drug combinations with synthesized EPD, cisplatin and paclitaxel were studied in four ovarian cell lines, and normal fibroblasts. EPD showed in particular strength in its effects with the cisplatin resistant cell line COV362 cl 4 and with a paclitaxel resistant cell line A2780. Compared to cisplatin and paclitaxel, less effects of EPD were shown to effect the viability of normal fibroblasts. Synthesized EPD proved to be promising both as an anti-ovarian cancer agent as well as a chemo-sensitizing agent in combination with other anti-cancer drugs. Synthesized EPD will facilitate pre-clinical studies.

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Section: Epd Synthesismentioning

confidence: 99%

“…Measurements were performed using a non-uorescent substrate, Presto Blue (Bio Source, Invitrogen, UK) and based on dose response curves. Synergistic drug combinations with EPD and cisplatin or paclitaxel were also performed and caused apoptosis [10,11].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of EPD, an established cytotoxic agent for ovarian cancer cells, and its efficacy in cisplatin and paclitaxel resistant tumor cells

Haaften,

Koek,

Eendenburg

et al. 2023

Preprint

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show abstract

“…Most BRCA1 and BRCA2 mutations confer a moderate radiosensitivity in G1 comparable to that observed in the case of MRE11 mutations [ 201 ]. Some mutations of BRCA1 and BRCA2 are also associated with high chemosensitivities, particularly to alkylating agents such as cis-platinum [ 201 , 202 ]. However, some studies about the RI cascade of phosphorylations of ATM substrates show that BRCA1 and BRCA2 should be considered more as cell cycle checkpoint proteins than as DNA repair proteins since the kinetics of RI phosphorylation of BRCA1/2 proteins are slower than the molecular events involved in DNA damage recognition and repair [ 15 ].…”

Section: Diseases Of Cell Cycle Checkpoint Controlmentioning

confidence: 99%

Cancer and Radiosensitivity Syndromes: Is Impaired Nuclear ATM Kinase Activity the Primum Movens?

Nachef

Berthel

Ferlazzo

et al. 2022

Cancers

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There are a number of genetic syndromes associated with both high cancer risk and clinical radiosensitivity. However, the link between these two notions remains unknown. Particularly, some cancer syndromes are caused by mutations in genes involved in DNA damage signaling and repair. How are the DNA sequence errors propagated and amplified to cause cell transformation? Conversely, some cancer syndromes are caused by mutations in genes involved in cell cycle checkpoint control. How is misrepaired DNA damage produced? Lastly, certain genes, considered as tumor suppressors, are not involved in DNA damage signaling and repair or in cell cycle checkpoint control. The mechanistic model based on radiation-induced nucleoshuttling of the ATM kinase (RIANS), a major actor of the response to ionizing radiation, may help in providing a unified explanation of the link between cancer proneness and radiosensitivity. In the frame of this model, a given protein may ensure its own specific function but may also play additional biological role(s) as an ATM phosphorylation substrate in cytoplasm. It appears that the mutated proteins that cause the major cancer and radiosensitivity syndromes are all ATM phosphorylation substrates, and they generally localize in the cytoplasm when mutated. The relevance of the RIANS model is discussed by considering different categories of the cancer syndromes.

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Parthenolide and its Analogues: A New Potential Strategy for the Treatment of Triple-Negative Breast Tumors

Araújo

Vecchi

Lima

et al. 2020

CMC

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Triple negative breast cancers (TNBC) are heterogeneous and aggressive pathologies, with distinct morphological and clinical characteristics associated with their genetic diversity, epigenetics, transcriptional changes and aberrant molecular patterns. Treatment with anti-neoplastic drugs exerts systemic effects with low specificity, and incipient improvement in overall survival due to chemoresistance and recurrence. New alternatives for TNBC treatment are urgent and parthenolide or its analogues have been explored. Parthenolide is a sesquiterpene lactone with promising antitumor effects against TNBC cell lines. This review highlights the importance of parthenolide and its analogue drugs in TNBC treatment.

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Chemosensitivity of BRCA1-Mutated Ovarian Cancer Cells and Established Cytotoxic Agents

Cited by 3 publications

References 27 publications

Synthesis of EPD, an established cytotoxic agent for ovarian cancer cells, and its efficacy in cisplatin and paclitaxel resistant tumor cells

Synthesis of EPD, an established cytotoxic agent for ovarian cancer cells, and its efficacy in cisplatin and paclitaxel resistant tumor cells

Cancer and Radiosensitivity Syndromes: Is Impaired Nuclear ATM Kinase Activity the Primum Movens?

Parthenolide and its Analogues: A New Potential Strategy for the Treatment of Triple-Negative Breast Tumors

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