Small molecule heat shock protein 27 inhibitor J2 decreases ovarian cancer cell proliferation via induction of apoptotic pathways

KARADEMİR, Dilay; Özgür, Aykut

doi:10.1007/s12032-023-02126-2

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…HSP27 is one of the well-known cell survival genes, and its expression decreases in cancer cells undergoing apoptosis [ 31 ]. HSP27 is a cell survival factor that is synthesized in response to cytotoxic stimuli and plays an important role in maintaining cell function in the absence of stress.…”

Section: Discussionmentioning

confidence: 99%

Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells

Cho,

Sun,

et al. 2024

Medicines

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Background: This study investigated how the expression of heat shock protein 27 (HSP27), cellular FLICE-like inhibitory protein (cFLIP), and clusterin (CLU) affects the progression of cancer cells and their susceptibility to doxazosin-induced apoptosis. By silencing each of these genes individually, their effect on prostate cancer cell viability after doxazosin treatment was investigated. Methods: PC-3 prostate cancer cells were cultured and then subjected to gene silencing using siRNA targeting HSP27, cFLIP, and CLU, either individually, in pairs, or all together. Cells were then treated with doxazosin at various concentrations and their viability was assessed by MTT assay. Results: The study found that silencing the CLU gene in PC-3 cells significantly reduced cell viability after treatment with 25 µM doxazosin. In addition, the dual silencing of cFLIP and CLU decreased cell viability at 10 µM doxazosin. Notably, silencing all three genes of HSP27, cFLIP, CLU was most effective and reduced cell viability even at a lower doxazosin concentration of 1 µM. Conclusions: Taken together, these findings suggest that the simultaneous silencing of HSP27, cFLIP, and CLU genes may be a potential strategy to promote apoptosis in prostate cancer cells, which could inform future research on treatments for malignant prostate cancer.

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Section: Discussionmentioning

confidence: 99%

Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells

Cho,

Sun,

et al. 2024

Medicines

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show abstract

“…Even today, the mechanisms responsible for resistance in ovarian cancer treatment are poorly understood ( Cornelison et al, 2017 ). Regarding acquired resistance, the deregulation of anti-apoptotic genes Bcl-2 and Bcl-xL has been well established ( Dai et al, 2023 ; Karademir and Özgür, 2023 ). Expression of both genes is regulated by post-transcriptional mechanisms, including the interactions between stabilizing or destabilizing RNA-binding proteins (RBP) and their mRNAs ( Cui and Placzek, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting z-Crystallin by aspirin restores the sensitivity to cisplatin in resistant A2780 ovarian cancer cells

Lulli,

Trabocchi,

Roviello

et al. 2024

Front. Pharmacol.

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Ovarian cancer is the deadliest gynaecologic malignancies worldwide. Platinum based chemotherapy is the mainstay treatment for ovarian cancer; however, frequent recurrence and chemoresistance onset in patients with advanced diseases remain a therapeutic challenge. Although mechanisms underlying the development of chemoresistance are still ambiguous, the B-cell lymphoma-2 (Bcl-2) family is closely associated with chemoresistance in ovarian cancer. We previously disclosed that Zeta-Crystallin (CryZ) is a post-transcriptional regulator of Bcl-2 gene expression, by binding to Bcl-2 mRNA and increasing its half-life. Here, we investigated the role of CryZ as a novel therapeutic target in A2780 ovarian carcinoma cells by modulating the protein activity with acetylsalicylic acid (ASA) to restore chemosensitivity. Molecular docking and fragment-mapping based approach revealed potential interaction of ASA within CryZ protein. Inhibition of CryZ binding activity to Bcl-2 and Bcl-xl mRNA targets by ASA was demonstrated in A375 cells. Cytotoxicity assays were conducted in A2780S and A2780R ovarian cancer cells to evaluate if CryZ binding activity inhibition and CryZ silencing were able to reverse cisplatin resistance. ASA-treatment determined a downregulation of Bcl-2 and Bcl-xl mRNA levels in A2780S and A2780R cells. ASA-treatment or CryZ silencing were able to increase and restore the chemosensitivity in both sensitive and resistant A2780 ovarian cancer cells, respectively. In this research article we demonstrated that the pharmacological or genetic inhibition of CryZ restores the sensitivity to cisplatin in a model of sensitive or resistant ovarian cancer cells. These findings suggest a new gene-targeted chemotherapeutic approach to restore the cytotoxicity in drug-resistant ovarian cancers and increase the sensitivity in non-resistant cells.

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Therapeutic potential of ASK1 activators in cancer treatment: Current insights and future directions

Wang,

Ma,

Zhang

et al. 2024

Biomedicine & Pharmacotherapy

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Small molecule heat shock protein 27 inhibitor J2 decreases ovarian cancer cell proliferation via induction of apoptotic pathways

Cited by 5 publications

References 48 publications

Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells

Triple Silencing of HSP27, cFLIP, and CLU Genes Promotes the Sensitivity of Doxazosin-Induced Apoptosis in PC-3 Prostate Cancer Cells

Targeting z-Crystallin by aspirin restores the sensitivity to cisplatin in resistant A2780 ovarian cancer cells

Therapeutic potential of ASK1 activators in cancer treatment: Current insights and future directions

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