Implications of apoptosis regulators in tumorigenesis

Malaguarnera, Lucia

doi:10.1023/b:canc.0000031774.32572.df

Cited by 56 publications

(46 citation statements)

References 97 publications

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“…In addition, although parthenolide, an inhibitor of NF-nB, has also shown antimetastatic activity in vitro (21,30), there have been few reports about its in vivo antimetastatic activity or its mode of action (22). Our in vivo experiments showed the following: (a) lung metastasis was suppressed when parthenolide was given It is now recognized that resistance to cell death, particularly apoptotic cell death, is an important aspect of metastatic progression (31). During the multistep metastatic cascade, it is believed that tumor cells withstand severe proapoptotic pressures from host cell cytokines and growth factors (32)(33)(34).…”

Section: Discussionmentioning

confidence: 73%

Parthenolide, a Natural Inhibitor of Nuclear Factor-κB, Inhibits Lung Colonization of Murine Osteosarcoma Cells

Kishida

Yoshikawa

Myoui

2007

Clinical Cancer Research

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Purpose: The transcription factor nuclear factor-nB (NF-nB) regulates the expression of several genes important for tumor metastasis and is constitutively active in the highly metastatic murine osteosarcoma cell line LM8. Parthenolide, a sesquiterpene lactone, was reported to inhibit the DNA binding of NF-nB. The purpose of this study is to investigate the usefulness of parthenolide as target for antimetastatic therapies. Experimental Design: We examined the effect of parthenolide on metastasis-associated phenotypes in vitro and in murine experimental lung metastasis models by s.c. and i.v. inoculation of LM8 cells. Results: We found that parthenolide strongly induced apoptosis and inhibited cell proliferation and the expression of vascular endothelial growth factor in vitro. In the in vivo metastasis models, parthenolide treatment suppressed lung metastasis when treatment was initiated concurrently with s.c. or i.v. inoculation of tumor cells, whereas lung metastasis was not reduced when parthenolide was given after the homing of tumor cells. The growth of s.c. tumors that developed at the inoculation site was not suppressed by parthenolide.We also found that the genetic inhibition of NF-nB activity by expressing mutant InBa suppressed lung metastasis in vivo but not s.c. tumor growth. This supports our notion that the metastasis-preventing effect of parthenolide is mediated at least in part by inhibition of NF-nB activity. Conclusions: These findings suggested that NF-nB is a potential molecular target for designing specific prophylactic interventions against distant metastasis and that parthenolide is a hopeful candidate for an antimetastatic drug.Osteosarcoma is the most common primary bone malignancy affecting children and young adults. The biggest difficulty with osteosarcoma is its high propensity for pulmonary metastasis. Patients with extremity lesions in whom lung metastases are detected at the time of diagnosis have a very poor prognosis. Modern multidisciplinary therapy has improved their outlook; however, up to half of the patients with osteosarcoma are still not cured. Thus, clarification of the molecular mechanism of pulmonary metastasis of osteosarcoma and introduction of a new intervention method are still needed (1).Previously, we showed that LM8, a highly metastatic subclone of the Dunn murine osteosarcoma cell line, overexpressed valosin-containing protein (also known as p97) and exhibited increased nuclear factor-nB (NF-nB) activity (2). The transfection of valosin-containing protein in Dunn osteosarcoma cells could activate NF-nB and its metastatic potential. We also reported that the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase, which were regulated by NF-nB, was up-regulated in LM8 and in Dunn cells transfected with valosin-containing protein compared with original Dunn cells (3). These findings suggested that therapy against NF-nB activity is a prime target and has the potential to improve the prognosis of osteosarcoma.NF-nB is an inducibl...

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Section: Discussionmentioning

confidence: 73%

Parthenolide, a Natural Inhibitor of Nuclear Factor-κB, Inhibits Lung Colonization of Murine Osteosarcoma Cells

Kishida

Yoshikawa

Myoui

2007

Clinical Cancer Research

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“…In order for the comparison of individual time points, data were assayed by variance (ANOVA) and an unpaired Student's t-test (29). Survival analysis was computed by the Kaplan-Meier method and compared by the log-rank test (30). A P-value of <0.05 was considered to indicate a statistically significant difference.…”

Section: Murine Tumor Model and Treatment Lewis Lung Carcinoma (Llc)mentioning

confidence: 99%

Live attenuated measles virus vaccine induces apoptosis and promotes tumor regression in lung cancer

et al. 2012

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Abstract. Although the treatment of lung carcinoma has improved, at least 65% of patients with this tumor succumb to progressive disease. Measles virus oncolytic therapy has been reported to be effective in reducing tumor burden in immunocompetent or nude mice; however, its potential to reduce tumor burden in lung carcinoma remains to be determined. Herein, we report the potent antitumor effects of a live attenuated measles vaccine virus Hu-191 strain (MV) against lung carcinoma. Immunocompetent C57BL/6 mice bearing Lewis lung carcinoma (LLC) cells were treated with MV (1x10 4 to 1x10 6 CCID 50 /ml) once every other day for 10 days. Our results showed that treatment with MV effectively suppressed tumor growth and significantly prolonged the survival time of tumorbearing animals. Histological examination revealed that the antitumor effects of MV therapy may result from increased induction of apoptosis, tumor necrosis and elevated lymphocyte infiltration. Our data suggest that MV, one of the widely used vaccines in China, has the ability to inhibit the growth of mouse lung carcinoma and may prove useful in the further exploration of the application of this approach in the treatment of human advanced lung cancer.

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“…Signal transduction molecules that mediate cell fate decisions have come under scrutiny as potential targets for cancer therapy as their perturbation affords cancer cells increased growth potential and the ability to avert apoptosis (18,20). In this regard, the PI3K/ Akt signal transduction pathway is a good candidate for treatment in many cancer types (11,21).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of phosphatidylinositol 3-kinase sensitizes ovarian cancer cells to carboplatin and allows adjunct chemotherapy treatment

Westfall

Skinner

2005

Molecular Cancer Therapeutics

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Signal transduction pathways associated with cancer progression and chemotherapeutic resistance are being investigated as molecular targets for chemotherapy. The phosphatidylinositol 3-kinase (PI3K) pathway has been found to be frequently amplified and have increased activity in ovarian cancer. The current study investigates the efficacy of an antagonist of PI3K, LY294002, in inhibiting ovarian cancer cell growth and survival both in vitro and in vivo. The hypothesis tested is that inhibition of PI3K signaling makes ovarian cancer cells susceptible to the effects of platinum-based chemotherapy. Observations show that LY294002 is an effective inhibitor of ovarian cancer cell growth and survival in vitro. Inhibition of PI3K/Akt signaling increased the sensitivity of ovarian cell cultures to the cytotoxic effects of carboplatin. The combined treatment of LY294002 and carboplatin was needed to optimally promote cellular apoptosis and decrease ovarian cancer cell survival in vitro. To extend these observations, a model involving in vivo i.p. growth of human ovarian tumors in a nude mouse was used. LY294002 in combination with carboplatin was more effective in inhibiting ovarian cancer cell xenograft growth than either agent alone. The results of this study suggest that the combined treatment of carboplatin and LY294002 can effectively decrease ovarian tumor progression and support the use of a PI3K inhibitor (e.g., LY294002) as an adjunct platinum-based drug therapy for treatment of ovarian cancer. [Mol Cancer Ther 2005;4(11):1764 -71]

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Implications of apoptosis regulators in tumorigenesis

Cited by 56 publications

References 97 publications

Parthenolide, a Natural Inhibitor of Nuclear Factor-κB, Inhibits Lung Colonization of Murine Osteosarcoma Cells

Parthenolide, a Natural Inhibitor of Nuclear Factor-κB, Inhibits Lung Colonization of Murine Osteosarcoma Cells

Live attenuated measles virus vaccine induces apoptosis and promotes tumor regression in lung cancer

Inhibition of phosphatidylinositol 3-kinase sensitizes ovarian cancer cells to carboplatin and allows adjunct chemotherapy treatment

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