KNK437, a benzylidene lactam compound, sensitises prostate cancer cells to the apoptotic effect of hyperthermia

Şahin, Emine; Şahin, Mehmet; Şanlioğlu, Ahter Dilşad; Gümüşlü, Saadet

doi:10.3109/02656736.2010.528139

Cited by 19 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Quercetin, a kind of flavanoid, inhibited HSPs expression in many kinds of cancer cells [42,43]. Cells became more susceptible to apoptosis when treated with quercetin followed by hyperthermia, chemotherapy or radiotherapy [44-46]. But quercetin showed significant toxicity even used as a signal agent, which largely limited its clinical application.…”

Section: Discussionmentioning

confidence: 99%

Blockade of PI3K/AKT pathway enhances sensitivity of Raji cells to chemotherapy through down-regulation of HSP70

Fang

Jiang

et al. 2013

Cancer Cell Int

View full text Add to dashboard Cite

Up-regulation of heat shock protein 70 (HSP70) could be elicited primarily by heat in former studies, and this was proved to be associated with cancer progression. Burkitt's lymphoma is one of highly aggressive B-cell non-Hodgkin’s lymphoma and is one of the fastest growing human tumors. To investigate the effect of HSP70 expression on the sensitivity of human Burkitt lymphoma cells (Raji cells) to chemotherapy and its role in the involvement of PI3K/AKT pathway, we evaluated the effects of LY294002, a PI3K inhibitor, on the expression of HSP70 and cell sensitivity to adriamycin (ADM) or cisplatin (DDP). In present study, expressions of HSP70, AKT and phosphorylated AKT (p-AKT) in Raji cells were measured by Western-Blot. Apoptosis index of Raji cells was examined by flow cytometry. Cytotoxicities of adriamycin (ADM) and cisplatin (DDP) were determined by WST-8 assay. We found that hyperthermia (42 degrees for 1 hour) up-regulated the expression of HSP70 expression and blockade of PI3K/AKT pathway down-regulated HSP70 expression in Raji cells. Compared to cells treated with ADM or DDP alone, hyperthermia protected cells from chemotherapy while LY294002 enhanced sensitivity of Raji cells to chemotherapy. Our results suggested down-regulation of HSP70 expression by blockade of PI3K/AKT pathway maybe responsible for the increased sensitivity of Raji cells to chemotherapy. Targeting PI3K/AKT pathway or inhibiting HSP70 expression may be beneficial for chemotherapy treatment of Burkitt lymphoma patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Blockade of PI3K/AKT pathway enhances sensitivity of Raji cells to chemotherapy through down-regulation of HSP70

Fang

Jiang

et al. 2013

Cancer Cell Int

View full text Add to dashboard Cite

show abstract

“…The production of Hsp70 assists in repairing and stabilising damaged proteins by correcting their 3D folding, permitting continued functions under stress [57–59]. In this scenario, cancer cell survival is increased and a greater focus is placed on the inhibition of Hsp70 for therapeutic approach [60]. …”

Section: Discussionmentioning

confidence: 99%

Role of Pluronic block copolymers in modulation of heat shock protein 70 expression

Perera

Krupka

et al. 2011

International Journal of Hyperthermia

View full text Add to dashboard Cite

Purpose The goal of this study was to evaluate the relationship between previously demonstrated thermosensitising effects of the block copolymer, Pluronic, and heat shock protein 70 (Hsp70) expression in an experimental colorectal cancer model in vitro and in vivo. Materials and methods Rat colorectal carcinoma cells were treated with low-grade hyperthermia (43°C) alone or in combination with Pluronics L10 (3 mg/mL), L61 (0.3 mg/mL), or L64 (0.5 mg/mL) for 20 min. Adinosine triphosphate (ATP) levels and cell viability were determined using standard assays. Hsp70 expression was quantified by western blot for cells treated with L10, L61, and L64 at doses specified above and Pluronic P85 (10 mg/mL) alone and in combination with heat. BDIX rats with flank tumours were used to study the effect of L61 and hyperthermia on Hsp70 expression in vivo. Results In vitro, treatment with L10, L61, and L64 plus low-grade hyperthermia lead to depletion of ATP levels to between 8 and 66% of untreated control after 24 h. Maximum expression of Hsp70 was observed at 9 h following hyperthermia alone. The combination of low-grade hyperthermia and Pluronic treatment reduced Hsp70 expression for up to 6 hours, and L10 appeared to completely inhibit the Hsp70 expression. In vivo, Hsp70 expression was increased 5 h after hyperthermia in BDIX rat tumour models and no Hsp70 expression was observed in L61 pre-treated and control groups. Conclusion Pluronic effectively improves hyperthermic and low-grade hyperthermic treatment in part due to reduction of Hsp70 expression.

show abstract

“…Of Note, the HSP inhibitor KNK437, a benzylidene lactam compound, was observed to dramatically reduce expression of Hsp27 in gemcitabine-resistant pancreatic cancer cells KLM1-R and to enhance the in vitro anti-tumor cytotoxic effect of gemcitabine on KLM1-R compared to single-agent gemcitabine (Taba et al, 2011). KNK437 also sensitizes prostate cancer cells to the apoptotic effect of hyperthermia by down-regulating heat-induced Hsp70 mRNA expression (Sahin et al, 2011). Moreover, in patients with locally advanced squamous-cell esophageal cancer neoadjuvant radiochemotherapy (NRCT) led to a decreased expression of Hsp16.2, Hsp90, and heme-binding protein 2 (SOUL), and an increased Bax/Bcl-2 ratio was found in the responding tumors (Farkas et al, 2011).…”

Section: Targeting Of Heat Shock Proteins In Radiotherapymentioning

confidence: 99%

Radiation, Inflammation, and Immune Responses in Cancer

Multhoff¹,

Radons²

2012

Front. Oncol.

162

128

View full text Add to dashboard Cite

Chronic inflammation has emerged as one of the hallmarks of cancer. Inflammation also plays a pivotal role in modulating radiation responsiveness of tumors. As discussed in this review, ionizing radiation (IR) leads to activation of several transcription factors modulating the expression of numerous mediators in tumor cells and cells of the microenvironment promoting cancer development. Novel therapeutic approaches thus aim to interfere with the activity or expression of these factors, either in single-agent or combinatorial treatment or as supplements of the existing therapeutic concepts. Among them, NF-κB, STAT-3, and HIF-1 play a crucial role in radiation-induced inflammatory responses embedded in a complex inflammatory network. A great variety of classical or novel drugs including nutraceuticals such as plant phytochemicals have the capacity to interfere with the inflammatory network in cancer and are considered as putative radiosensitizers. Thus, targeting the inflammatory signaling pathways induced by IR offers the opportunity to improve the clinical outcome of radiation therapy by enhancing radiosensitivity and decreasing putative metabolic effects. Since inflammation and sex steroids also impact tumorigenesis, a therapeutic approach targeting glucocorticoid receptors and radiation-induced production of tumorigenic factors might be effective in sensitizing certain tumors to IR.

show abstract

KNK437, a benzylidene lactam compound, sensitises prostate cancer cells to the apoptotic effect of hyperthermia

Cited by 19 publications

References 27 publications

Blockade of PI3K/AKT pathway enhances sensitivity of Raji cells to chemotherapy through down-regulation of HSP70

Blockade of PI3K/AKT pathway enhances sensitivity of Raji cells to chemotherapy through down-regulation of HSP70

Role of Pluronic block copolymers in modulation of heat shock protein 70 expression

Radiation, Inflammation, and Immune Responses in Cancer

Contact Info

Product

Resources

About