Heat‐induced membrane damage combined with adriamycin on prostate carcinoma PC‐3 cells: correlation of cytotoxicity, permeability and P‐glycoprotein or metallothionein expression

Moriyama‐Gonda,; Igawa,; Shiina,; Wada, Yasuhiro

doi:10.1046/j.1464-410x.1998.00951.x

Cited by 15 publications

(10 citation statements)

References 15 publications

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“…OPN seems to play an important role in chemoresistance. In our study, OPN could upregulate P-gp expression, which is present in PC-3 cell membrane and cytoplasm (Moriyama-Gonda et al, 1998), and also increased P-gp expression in DU145 prostate cancer cells (Supplemental Fig. 2).…”

Section: Discussionsupporting

confidence: 59%

Upregulation of Drug Transporter Expression by Osteopontin in Prostate Cancer Cells

et al. 2013

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Multidrug resistance is a major cause of chemotherapy failure. Recent studies indicate that drug resistance can be rapidly induced by some soluble factors, such as cytokines, chemokines, growth factors, and cell adhesion factors in the tumor microenvironment. Osteopontin (OPN), an extracellular matrix protein, has a functional arginine-glycine-aspartic acid (RGD) domain for binding to integrin. Here we found OPN expression to be upregulated by hypoxic condition in PC-3 prostate tumor cells. OPN increased the mRNA and protein expression of pglycoprotein (P-gp), a subfamily of ATP-binding cassette transporter in a concentration-and time-dependent manner. The increase in P-gp transporter by OPN was mediated by binding to avb3 integrin. Daunomycin (DUN), a chemotherapeutic agent with autofluorescence, was used to evaluate the pump activity, and OPN increased the drug pumping-out activity. OPN inhibited DUN-induced cell death, which was antagonized by avb3 monoclonal antibody. Long-term treatment with DUN further enhanced the expression of OPN. Knockdown of endogenous OPN potentiated the DUN-induced apoptosis of PC-3 cells. Furthermore, knockdown of OPN enhanced cell death caused by other drugs, including paclitaxel, doxorubicin, actinomycin-D, and rapamycin, which are also P-gp substrates. The animal studies also showed that OPN knockdown enhanced the cytotoxic action of DUN. These results indicate that OPN is a potential therapeutic target for cancer therapy to reduce drug resistance in sensitive tumors.

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Section: Discussionsupporting

confidence: 59%

Upregulation of Drug Transporter Expression by Osteopontin in Prostate Cancer Cells

et al. 2013

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“…Moriyama-Gonda et al 43 showed that heating might induce a reduction in P-gp expression, leading to inhibition of , or verapamil at 37 C (ver) on cellular uptake of R123 and doxorubicinby the parentor MDR variants of MV522 and KB cell lines.Cellularuptake dataare presentedas accumulationfactor. Accumulation factor for control cells is defined as equal to1.…”

Section: Ultrasound As Adjuvant To Overcome the Clinical Effects Of Mmentioning

confidence: 99%

Therapeutic ultrasound: Its application in drug delivery

Ng¹,

Liu²

2002

Medicinal Research Reviews

157

110

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Ultrasound is best known for its imaging capability in diagnostic medicine. However, there have been considerable efforts recently to develop therapeutic uses for it. The purpose of this review is to summarize some of the recent advances made in the area of therapeutic ultrasound as they relate to drug delivery. In particular, this review will focus on the applications of ultrasound to enhance the delivery and effect of three distinctive therapeutic drug classes: chemotherapeutic, thrombolytic, and gene-based drugs. In addition, ultrasound contrast agents have been recently developed for diagnostic ultrasound. New experimental evidence suggests that these contrast agents can be used as exogenous cavitation nuclei for enhancement of drug and gene delivery. Thus, brief review of this new class of agents and their roles in drug delivery will also be provided. By comparison to diagnostic ultrasound, progress in therapeutic use of ultrasound has been somewhat limited. The recent successes in ultrasound-related drug delivery research positions ultrasound as therapeutic tool for drug delivery in the future.

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“…Furthermore in PC-3 prostate carcinoma cells, a hyperthermia-induced downregulation of P-glycoprotein was observed. 15 These conflicting date indicate that a more detailed analysis of hyperthermia regulation of Pglycoprotein as well as the underlying signaling cascades is necessary.In previous studies, we have reported on the development of an intrinsic P-glycoprotein-mediated MDR in multicellular tumor spheroids, which is repressed in small spheroids by low level endogenous ROS generation and upregulated in large tumor spheroids by central hypoxia and HIF-1␣. 16 -18 However, we and others demonstrated that on the other hand high concentrations of ROS conferring oxidative stress resulted in an induction of the mdr-1 gene and upregulation of P-glycoprotein.…”

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confidence: 99%

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confidence: 99%

Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species

Wartenberg

Gronczynska

Bekhite

et al. 2004

Intl Journal of Cancer

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Hyperthermia is an important component of many cancer treatment protocols. In our study the regulation of the multidrug resistance (MDR) transporter P-glycoprotein by hyperthermia was studied in multicellular prostate tumor spheroids. Hyperthermia treatment of small (50 -100 m) tumor spheroids significantly increased P-glycoprotein and mdr-1 mRNA expression with a maximum effect at 42°C, whereas only moderate elevation of P-glycoprotein was found in large (350 -450 m) tumor spheroids. Hyperthermia caused an elevation of intracellular reactive oxygen species (ROS). Inhibition of ROS generation with NADPH-oxidase inhibitors diphenylen iodonium (DPI) and 4-(2-aminoethyl)benzenesulfonyl fluoride (AEBSF) abolished P-glycoprotein expression but did not affect its transcript levels following heat treatment. This indicates that P-glycoprotein levels are controlled by regulating its translation rate or stability. Hyperthermia incubation resulted in a differential activation of p38 mitogen-activated protein kinase (MAPK), extracellular regulated kinase 1,2 (ERK1,2), and c-jun N-terminal kinase (JNK) immediately, 4 hr and 24 hr after treatment. Furthermore, upregulation of hypoxia-inducible factor 1␣ (HIF-1␣) was observed. Elevation of HIF-1␣ and Pglycoprotein expression following hyperthermia treatment were abolished upon coadministration of the p38 inhibitor SB203580. In contrast the JNK inhibitor SP600125 and the ERK1,2 inhibitor UO126 resulted in increase of HIF-1␣ and P-glycoprotein in the control as well as the hyperthermia-treated samples, indicating negative regulation of intrinsic HIF-1␣ and P-glycoprotein expression by ERK1,2 and JNK signaling cascades. In summary our data demonstrate that hyperthermia-induced upregulation of P-glycoprotein and HIF-1␣ is mediated by activation of p38, whereas ERK1,2 and JNK are involved in repression of P-glycoprotein and HIF-1␣ under control conditions. Key words: multidrug resistance; P-glycoprotein; hyperthermia; hypoxia-inducible factor 1-␣ Hyperthermia in combination with chemotherapy and radiotherapy has been previously successfully used in anti-cancer strategies. [1][2][3][4][5] The efficiency of chemotherapeutic as well as radiotherapeutic cancer treatment is generally restricted by the expression of MDR transporters that confer resistance to a variety of structurally unrelated, clinically important antineoplastic agents. 6 -8 The most clinically significant MDR transporter P-glycoprotein, a 170 kDa ATP-dependent membrane-bound transporter, has been recently demonstrated to be upregulated by hyperthermia. 9,10 The promotor of the mdr-1 gene, which encodes for P-glycoprotein, harbors different responsive elements that are inducible by various stress factors including hyperthermia. 11 In this respect, it has been previously demonstrated in colon cancer cells that hyperthermia resulted in nuclear translocation of the Y-box transcription factor YB-1 and enhanced expression of mdr-1. 12 Binding of hyperthermia factors to defined heat shock element (HSE) motifs of the mdr-1 pr...

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Heat‐induced membrane damage combined with adriamycin on prostate carcinoma PC‐3 cells: correlation of cytotoxicity, permeability and P‐glycoprotein or metallothionein expression

Cited by 15 publications

References 15 publications

Upregulation of Drug Transporter Expression by Osteopontin in Prostate Cancer Cells

Upregulation of Drug Transporter Expression by Osteopontin in Prostate Cancer Cells

Therapeutic ultrasound: Its application in drug delivery

Regulation of the multidrug resistance transporter P‐glycoprotein in multicellular prostate tumor spheroids by hyperthermia and reactive oxygen species

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