The PI3K/AKT/mTOR-Signal Transduction Pathway as Drug Target in Triple-Negative Breast Cancer

Hahne, Jens C.; Engel, J.; Hönig, Arnd; Meyer, Susanne; Zito, Domenico; Lampis, Andrea; Valeri, Nicola

doi:10.2174/2212697x04666170321112629

Cited by 6 publications

(5 citation statements)

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Section: Introductionmentioning

confidence: 99%

“…This subtype of breast cancer is characterized by a lack of expression of both oestrogen and progesterone receptors with simultaneous absence of human epidermal growth factor 2 (HER2) receptors . Indeed, TNBC tumors are not sensitive to standard therapies since they do not express the relevant receptors (ER, PR, HER) . Currently, conventional‐targeted breast treatment offers only limited benefits and might cause additional side‐effects; such treatment leaves them associated with a high rate of local and systemic relapse .…”

Section: Introductionmentioning

confidence: 99%

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Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Bouchmaa

Mrid²,

Boukharsa

et al. 2018

Archiv der Pharmazie

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Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H 2 O 2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC 50 values of 3.12 and 4.9 µM, respectively. Furthermore, cells exposed to 6f showed a significant increase in H 2 O 2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities.anticancer agent, cytotoxicity, oxidative stress, pyridazin-(2H)-3-ones, triple-negative breast cancer

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Bouchmaa

Mrid²,

Boukharsa

et al. 2018

Archiv der Pharmazie

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“…On the contrary, two cancer related proteins, such as, EGFR and HIF 1α, were found to be mainly expressed in the non-proliferating area of the tumor tissue. EGFR involves the growth of vessels ( Vara et al, 2004 ; Martini et al, 2014 ; Hahne et al, 2017 ) and HIF 1α protein is related to tissue hypoxia. The expression areas of cancer related proteins are related to the biological functions.…”

Section: Resultsmentioning

confidence: 99%

Quantitative Evaluation of in Vivo Target Efficacy of Anti-tumor Agents via an Immunofluorescence and EdU Labeling Strategy

Wen

Cui

et al. 2018

Front. Pharmacol.

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Current methods used to evaluate in vivo target efficacy of selected compound include western blot to semi-quantitatively analyze protein expression. However, problems arise as it is difficult to compare in vivo target efficacy of anti-tumor agents with the same mode of action. It is therefore desirable to develop a protocol that can quantitatively display in vivo target efficacy while also providing other useful information. In this study EdU labeling was used to mark out the proliferating area. The tumor tissue was accordingly divided into proliferating and non-proliferating areas. Fifteen tumor related proteins were stained by immunofluorescence and were found to express in either the proliferating or non-proliferating areas. This allows the quantitative analysis of protein expressions within the precise area. With simple image analysis, our method gave precise percent changes of protein expression and cell proliferation between the drugs treated group and the control group. Additional information, such as, the status of protein expression can also be obtained. This method exhibits high sensitivity, and provides a quantitative approach for in vivo evaluation of target efficacy.

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“…The most advanced PI3K pathway inhibitors are rapamycin analogs that specifically inhibit mTORC1 [19,20] . The relationship between the PI3K-AKT-mTOR pathway and cancer development, which induces the genetic variations as a result of bladder cancer risk, have been established [7,21] .…”

Section: Discussionmentioning

confidence: 99%

Naringin suppressing the PI3K/Akt signaling pathway as a drug target in BIU87 cells

Li¹,

Zhao²,

Zhang³

et al. 2020

Preprint

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Background: Flavonoids are regarded as potential anti-cancer drugs due to their toxicity and anti-proliferation functions. Naringin, which is a kind of flavanone compounds targeting anti-tumor treatment, has been focused on reliving several types of cancers, besides of bladder cancer. This paper was aimed to investigate whether and how naringin induced bladder cancer cells. Method: MTT, cell-cycle, transwell and cell apoptosis were used to assess the cellular responses. Molecular expressions and the signaling pathway of naringin inducing BIU87 cells were evaluated by western blot and real-time quantitative PCR. Results: It was found that naringin effectively suppressed proliferation and invasion of BIU87 cells by downregulating the expression of PI3K and its downstream pathway. The corresponding proteins related to viability and motility, including CDK2, Bcl-2 and Fascin, were inhibited. Conclusion: It can be concluded that naringin targeting to PI3K in bladder tumor cells expressed abundantly and inhibited the growth and invasive ability of tumor cells.

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The PI3K/AKT/mTOR-Signal Transduction Pathway as Drug Target in Triple-Negative Breast Cancer

Cited by 6 publications

References 0 publications

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Quantitative Evaluation of in Vivo Target Efficacy of Anti-tumor Agents via an Immunofluorescence and EdU Labeling Strategy

Naringin suppressing the PI3K/Akt signaling pathway as a drug target in BIU87 cells

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