Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator

Park, Hae-Ryong; Ryoo, In‐Ja; Choo, Soo‐Jin; Hwang, Ji‐Hwan; Kim, Ju‐Young; Cha, Mi-Ran; Shin‐ya, Kazuo; Yoo, Ick Dong

doi:10.1016/j.tox.2006.11.049

Cited by 47 publications

(37 citation statements)

References 33 publications

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“…Our results with siGRP78 show that lowering GRP78 levels significantly increases chemosensitivity to temozolomide. Recent developments of small molecules that can specifically block GRP78 expression and/or its activity may make this approach clinically feasible in the near future (9,(30)(31)(32)(33)(34). Recently, Ermakova et al (9) showed that EGCG, a major component of green tea, can bind to intracellular GRP78, inhibit its protective function, and increase chemosensitivity to etoposide in breast and bladder carcinoma cell lines.…”

Section: Discussionmentioning

confidence: 99%

The Unfolded Protein Response Regulator GRP78/BiP as a Novel Target for Increasing Chemosensitivity in Malignant Gliomas

Pyrko¹,

Schönthal²,

Hofman³

et al. 2007

Cancer Research

398

350

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Poor chemosensitivity and the development of chemoresistance remain major obstacles to successful chemotherapy of malignant gliomas. GRP78 is a key regulator of the unfolded protein response (UPR). As a Ca 2+ -binding molecular chaperone in the endoplasmic reticulum (ER), GRP78 maintains ER homeostasis, suppresses stress-induced apoptosis, and controls UPR signaling. We report here that GRP78 is expressed at low levels in normal adult brain, but is significantly elevated in malignant glioma specimens and human malignant glioma cell lines, correlating with their rate of proliferation. Down-regulation of GRP78 by small interfering RNA leads to a slowdown in glioma cell growth. Our studies further reveal that temozolomide, the chemotherapeutic agent of choice for treatment of malignant gliomas, leads to induction of CHOP, a major proapoptotic arm of the UPR. Knockdown of GRP78 in glioblastoma cell lines induces CHOP and activates caspase-7 in temozolomide-treated cells. Colony survival assays further establish that knockdown of GRP78 lowers resistance of glioma cells to temozolomide, and, conversely, overexpression of GRP78 confers higher resistance. Knockdown of GRP78 also sensitizes glioma cells to 5-fluorouracil and CPT-11. Treatment of glioma cells with (À)-epigallocatechin gallate, which targets the ATP-binding domain of GRP78 and blocks its protective function, sensitizes glioma cells to temozolomide. These results identify a novel chemoresistance mechanism in malignant gliomas and show that combination of drugs capable of suppressing GRP78 with conventional agents such as temozolomide might represent a novel approach to eliminate residual tumor cells after surgery and increase the effectiveness of malignant glioma chemotherapy. [Cancer Res 2007;67(20):9809-16]

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Section: Discussionmentioning

confidence: 99%

The Unfolded Protein Response Regulator GRP78/BiP as a Novel Target for Increasing Chemosensitivity in Malignant Gliomas

Pyrko¹,

Schönthal²,

Hofman³

et al. 2007

Cancer Research

398

350

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“…The fixed cells were washed with PBS, and stained with Hoechst 33342 (Sigma, St. Louis, MO, USA) for 1 h at room temperature. Then the cells were washed twice more with PBS, and the Hoechst-stained nuclei were excitation and emission wavelengths were set at 358 and 461 nm, respectively, visualized using a fluorescence microscope [11].…”

Section: Cell Stainingmentioning

confidence: 99%

“…HT-29 cells are the incomplete vascularization of tumor cells, and these cells frequently have regions of hypoxia and low levels of glucose and other nutrients due to an insufficient blood supply [8]. These stressful conditions cause limited anticancer activity during colon carcinoma cell treatment, because the cells, in such an aberrant environment, can survive and show drug resistance through a stress response characterized by stress protein [9][10][11]. It is widely recognized that both hypoglycemia and hypoxia generate resistance to anticancer agents, a principal problem in most cancer chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Methanolic Extracts of Uncaria rhynchophylla Induce Cytotoxicity and Apoptosis in HT-29 Human Colon Carcinoma Cells

Cha

Lee

et al. 2008

Plant Foods Hum Nutr

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In this paper, we report the anticancer activities of Uncaria rhynchophylla extracts, a Rubiaceae plant native to China. Traditionally, Uncaria rhynchophylla has been used in the prevention and treatment of neurotoxicity. However, the cytotoxic activity of Uncaria rhynchophylla against human colon carcinoma cells has not, until now, been elucidated. We found that the methanolic extract of Uncaria rhynchophylla (URE) have cytotoxic effects on HT-29 cells. The URE showed highly cytotoxic effects via the MTT reduction assay, LDH release assay, and colony formation assay. As expected, URE inhibited the growth of HT-29 cells in a dose-dependent manner. In particular, the methanolic URE of the 500 microg/ml showed 15.8% inhibition against growth of HT-29 cells. It induced characteristic apoptotic effects in HT-29 cells, including chromatin condensation and sharking occurring 24 h when the cells were treated at a concentration of the 500 microg/ml. The activation of caspase-3 and the specific proteolytic cleavage of poly (ADP-ribose) polymerase were detected over the course of apoptosis induction. These results indicate that URE contains bioactive materials with strong activity, and is a potential chemotherapeutic agent candidate against HT-29 human colon carcinoma cells.

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“…[11][12][13] Several genes are up-regulated upon UPR activation, such as glucose-regulated protein (GRP) 78 (also known as BiP) and ER-resident molecular chaperones. 14,15) Recently, several reports have indicated that GRP78 plays a role in protecting tumor cells against intracellular-mediated cytotoxicity.…”

mentioning

confidence: 99%

Selective Cytotoxicity of Ponciri Fructus against Glucose-Deprived PANC-1 Human Pancreatic Cancer CellsviaBlocking Activation of GRP78

Cha

Yoon

Son

et al. 2009

Bioscience, Biotechnology, and Biochemistry

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Glucose-deprived HT-29 human colon carcinoma cells are sensitive to verrucosidin as a GRP78 down-regulator

Cited by 47 publications

References 33 publications

The Unfolded Protein Response Regulator GRP78/BiP as a Novel Target for Increasing Chemosensitivity in Malignant Gliomas

The Unfolded Protein Response Regulator GRP78/BiP as a Novel Target for Increasing Chemosensitivity in Malignant Gliomas

Methanolic Extracts of Uncaria rhynchophylla Induce Cytotoxicity and Apoptosis in HT-29 Human Colon Carcinoma Cells

Selective Cytotoxicity of Ponciri Fructus against Glucose-Deprived PANC-1 Human Pancreatic Cancer CellsviaBlocking Activation of GRP78

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