Synergistic cytotoxic effect of quercetin and heat treatment in a lymphoid cell line (OZ) with low HSP70 expression

Fujita, Mitsuhiro; Nagai, Masami; Murata, Michio; Kawakami, Kimihiro; Irino, Shozo; Takahara, Jiro

doi:10.1016/s0145-2126(96)00080-x

Cited by 19 publications

(9 citation statements)

References 29 publications

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“…Present data constitutes the most original part of this study, since there is no study investigating the effect of KNK437 on caspase-3 and PARP levels in prostate cancer cells. These results suggest that the inhibition of Hsp70 which can suppress the caspase cascade derived from mitochondria [29] sensitises prostate cancer cells to heat-induced apoptosis.…”

Section: Discussionmentioning

confidence: 83%

“…Because there are only limited studies explaining the effects of KNK437 [25,27] and quercetin [28,29] on heat-induced cell death in some cell types, we focused on the relationships between KNK437 and apoptosis in prostate cancer cells. Nimmanapalli et al [27] reported that KNK437 caused more apoptosis in melphalan resistant 8226/ LR5 cells and sensitised them to melphalan.…”

Section: Discussionmentioning

confidence: 99%

“…Nimmanapalli et al [27] reported that KNK437 caused more apoptosis in melphalan resistant 8226/ LR5 cells and sensitised them to melphalan. Also, Fujita et al [29] reported that certain leukaemias were sensitive to heat, that whole body hyperthermia provided cell death successfully, and that quercetin (50 mM) enhanced heat-induced apoptosis in leukaemia cells. Apoptosis was induced by hyperthermia in both PC-3 and LNCaP cells.…”

Section: Discussionmentioning

confidence: 99%

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

Şahin

Şanlioğlu

et al. 2011

International Journal of Hyperthermia

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Hyperthermia is known to serve as a powerful tool in the treatment of prostate cancer which is commonly diagnosed in men. Quercetin and KNK437, Hsp70 inhibitors, play an important role in blocking thermotolerance in some cancer cells. In the present study we investigated the effects of KNK437 and quercetin on the acquisition of thermotolerance and heat-induced apoptosis. Also, it was examined whether the possible mechanism triggering apoptotic pathway included caspase-3 activation in prostate cancer cells. For this purpose, PC-3 and LNCaP cells were treated with hyperthermia following pretreatment with or without KNK437 or quercetin. Thermotolerance was investigated by colony formation assay in these cells, while Hsp70 mRNA levels were measured by real time RT-PCR. Sandwich ELISA was used for detection of Hsp70 protein levels. Apoptosis was detected by flow cytometric annexin V binding assay and by western blot analysis of procaspase-3 and cleaved poly (ADP-ribose) polymerase levels. In our study, KNK437 and quercetin inhibited thermotolerance in a dose-dependent manner in PC-3 cells. KNK437 and quercetin decreased heat-induced accumulation of Hsp70 mRNA and protein in PC-3 and LNCaP cells. KNK437 and quercetin pretreatment enhanced the apoptotic effect of hyperthermia in both cells. We found that KNK437 was more effective than quercetin in inducing apoptotic cell death, activation of caspase-3, and cleavage of PARP in prostate cancer cells. We suggest that KNK437 is a useful agent for enhancing the efficiency of hyperthermic therapy which has less toxic side-effects in prostate cancer.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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

Şahin

Şanlioğlu

et al. 2011

International Journal of Hyperthermia

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“…In vitro , flavonoids found in various food items of plant origin are known to be antiproliferative for various types of cancer cells, several animal studies and epidemiological studies have identified flavonoids as potential chemopreventive agents 8 . Quercetin, a synthetic flavonoid, has been shown to inhibit the stress response and especially inhibits the synthesis of hsp70 through the inhibition of heat‐shock‐transcription factor 1 or 2 10,11,20,21 . Several reports have shown that quercetin significantly enhances the cell‐killing effects of hyperthermia, 9,21,22 and increases heat‐induced apoptotic cell death by inhibiting hsp70 synthesis 23 .…”

Section: Discussionmentioning

confidence: 99%

“…Quercetin, a synthetic flavonoid, has been shown to inhibit the stress response and especially inhibits the synthesis of hsp70 through the inhibition of heat‐shock‐transcription factor 1 or 2 10,11,20,21 . Several reports have shown that quercetin significantly enhances the cell‐killing effects of hyperthermia, 9,21,22 and increases heat‐induced apoptotic cell death by inhibiting hsp70 synthesis 23 . In the present study, quercetin alone induced apoptosis, resulting in growth inhibitory effects and a decrease in total hsp70, leading to an increase in the number of subG1 cells with a lower level of hsp70 at concentrations of 50 μmol/L quercetin in JCA‐1 and LNcap cells 24 h after exposure.…”

Section: Discussionmentioning

confidence: 99%

Effects of quercetin on the heat‐induced cytotoxicity of prostate cancer cells

et al. 2001

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Background: It has been demonstrated that prostate cancer cells are relatively sensitive to heat stress. We have reported that heat treatment at 43°C increases the expression of heat shock protein 70 (hsp70) in prostate cancer cells, leading to apoptosis. Hsp70 is a protein that protects cells against heat damage. Cells with lower levels of hsp70 have been shown to have a higher sensitivity to heat stress. Therefore, downregulation of hsp70 is expected to enhance heat-induced inhibitory effects on cell growth. Quercetin has been reported to be an agent that inhibits hsp70 expression. The present study was undertaken to investigate the effects of quercetin and/or heat on the growth of prostate cancer cells in vitro. Conclusion:These results suggest that quercetin may enhance heat-induced cytotoxicity in prostate cancer cell lines through the inhibition of hsp70 production.

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Anticancer efficacies of doxorubicin, verapamil and quercetin on FM3A cells under hyperthermic temperature

Lee

Bae

Choi

et al. 2004

Biotechnol. Bioprocess Eng.

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Synergistic cytotoxic effect of quercetin and heat treatment in a lymphoid cell line (OZ) with low HSP70 expression

Cited by 19 publications

References 29 publications

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

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

Effects of quercetin on the heat‐induced cytotoxicity of prostate cancer cells

Anticancer efficacies of doxorubicin, verapamil and quercetin on FM3A cells under hyperthermic temperature

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