Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma

Huether, Alexander; Höpfner, Michael; Baradari, Viola; Schuppan, Detlef; Scherübl, Hans

doi:10.1016/j.bcp.2006.12.031

Cited by 70 publications

(56 citation statements)

References 32 publications

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“…Several multi-target kinase inhibitors, such as imatinib and sorafenib, have been in clinical use for cancer therapy. 51,52) Although the mechanisms and effects of Deltonin on cancer therapy need further clarificationin colon and other cancers, the present results have proved that Deltonin exerts its anti-cancer effects through multiple targets, which include the generation of ROS, inhibition of ERK and Akt signaling pathways, and direct mitochondrial apoptosis, suggesting Deltonin may have important potential as a cancer preventive and therapeutic agent. Vol.…”

Section: Discussionmentioning

confidence: 64%

Deltonin Isolated from Dioscorea zingiberensis Inhibits Cancer Cell Growth through Inducing Mitochondrial Apoptosis and Suppressing Akt and Mitogen Activated Protein Kinase Signals

Shu

Qing

Tong

et al. 2011

Biological & Pharmaceutical Bulletin

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Deltonin is an active component purified from Dioscorea zingiberensis WRIGHT (DZW), and has shown anticancer effects. However, its mechanism of action remains elusive. In the present study, we investigated the effect of Deltonin on a panel of cancer cell lines and analyzed its mechanism in C26 cells, a murine colon carcinoma cell. Our results showed that Deltonin markedly inhibited the growth of all examined cancer cell lines. Deltonin induced dose-and time-dependent apoptosis in C26 cells. The event of apoptosis was accompanied by the release of cytochrome c, depolarization of mitochondrial membrane potential, and dose-and time-dependent reactive oxygen species (ROS) generation. Deltonin also increased the expression of Bax, decreased the expression of Bcell lymphoma/lewkmia-2 (Bcl-2), and induced the activation of caspase 9, caspase 3 and poly(ADP-ribose) polymerase (PARP). Furthermore, Deltonin decreased Akt and extracellular signal-regulated kinase-1/2 (ERK 1/2 ) activity. These results demonstrate that Deltonin mediates the growth inhibition of cancer cells through multiple targets, which include the generation of reactive oxygen species (ROS), mitochondrial apoptosis and the inhibition of the mitogen-activated protein kinase (MAPK) and Akt signaling pathways, suggesting Deltonin is a potent cancer preventive and therapeutic agent.

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Section: Discussionmentioning

confidence: 64%

Deltonin Isolated from Dioscorea zingiberensis Inhibits Cancer Cell Growth through Inducing Mitochondrial Apoptosis and Suppressing Akt and Mitogen Activated Protein Kinase Signals

Shu

Qing

Tong

et al. 2011

Biological & Pharmaceutical Bulletin

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“…Up to now, the factors responsible for this relative unresponsiveness have not been clearly understood. In general, the efficacy of conventional anticancer therapies is strongly dependent on their ability to initiate programmed cell death (apoptosis) in cancer cells [6][7][8]. Therefore, cancer cells that have evolved ways to circumvent apoptosis become resistant, providing an obstacle to effective treatments [9,10].…”

Section: Introductionmentioning

confidence: 99%

Zoledronic acid determines S-phase arrest but fails to induce apoptosis in cholangiocarcinoma cells

Romani

Desenzani

Morganti

et al. 2009

Biochemical Pharmacology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. In conclusion, our study indicates that zoledronic acid induces S-phase arrest and cell-narrowing, both reversed by GGOH and, by changing the delicate balance between pro-apoptotic and antiapoptotic proteins, allows survival of cholangiocarcinoma cells.

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“…In 2007, Huther et al demonstrated that this drug inhibits the proliferation of human CC cell lines in a time-and dosedependent manner. This antiproliferative effect was correlated with the induction of cell death by apoptosis and cell cycle arrests in the G0/G1 phase [57]. In this experimental work, the authors were not able to draw more accurate conclusions about the mechanisms by which sorafenib induced the cell cycle's blockade and apoptosis; however, in 2005, another study had already provided some useful information [61].…”

Section: Diagnosis and Treatmentmentioning

confidence: 92%

“…Although in clinical practice sorafenib is not used in CC treatment, currently there are several studies which indicate that this drug has a promising role in the CC treatment [57][58][59][60]. Mutations in the MAPK signaling pathway are one of the most common genetic alterations in CC, present in approximately 60 % of cases of human tumors.…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

“…Mutations in the MAPK signaling pathway are one of the most common genetic alterations in CC, present in approximately 60 % of cases of human tumors. Within this signaling pathway, mutations in the RAS are described in about 56 % of these tumors and B-RAF mutations in about 22 %, which makes sorafenib a promising therapeutic weapon for CC treatment [57]. Indeed, there have been already performed in vitro studies that emphasize the potential effect of sorafenib on CC therapy.…”

Section: Diagnosis and Treatmentmentioning

confidence: 99%

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Cholangiocarcinoma: from molecular biology to treatment

et al. 2015

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Cholangiocarcinoma is a rare tumor originating in the bile ducts, which, according to their anatomical location, is classified as intrahepatic, extrahepatic and hilar. Nevertheless, incidence rates have increased markedly in recent decades. With respect to tumor biology, several genetic alterations correlated with resistance to chemotherapy and radiotherapy have been identified. Here, we highlight changes in KRAS and TP53 genes that are normally associated with a more aggressive phenotype. Also IL-6 and some proteins of the BCL-2 family appear to be involved in the resistance that the cholangiocarcinoma presents toward conventional therapies. With regard to diagnosis, tumor markers most commonly used are CEA and CA 19-9, and although its use isolated appears controversial, their combined value has been increasingly advocated. In imaging terms, various methods are needed, such as abdominal ultrasound, computed tomography and cholangiopancreatography. Regarding therapy, surgical modalities are the only ones that offer chance of cure; however, due to late diagnosis, most patients cannot take advantage of them. Thus, the majority of patients are directed to other therapeutic modalities like chemotherapy, which, in this context, assumes a purely palliative role. Thus, it becomes urgent to investigate new therapeutic options for this highly aggressive type of tumor.

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Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma

Cited by 70 publications

References 32 publications

Deltonin Isolated from Dioscorea zingiberensis Inhibits Cancer Cell Growth through Inducing Mitochondrial Apoptosis and Suppressing Akt and Mitogen Activated Protein Kinase Signals

Deltonin Isolated from Dioscorea zingiberensis Inhibits Cancer Cell Growth through Inducing Mitochondrial Apoptosis and Suppressing Akt and Mitogen Activated Protein Kinase Signals

Zoledronic acid determines S-phase arrest but fails to induce apoptosis in cholangiocarcinoma cells

Cholangiocarcinoma: from molecular biology to treatment

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