Erufosine, a novel alkylphosphocholine, induces apoptosis in CLL through a caspase-dependent pathway

Königs, Sonja Katharina; Pallasch, Christian P.; Lindner, Lars H.; Schwamb, Janine; Schulz, Alexandra; Brinker, Reinhild; Claasen, Julia; Veldurthy, Aditya; Eibl, H.; Hallek, Michael; Wendtner, Clemens‐Martin

doi:10.1016/j.leukres.2009.12.003

Cited by 25 publications

(22 citation statements)

References 23 publications

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“…Cytotoxic effects of Erufosine on chronic lymphocytic leukemia (CLL) and multiple myeloma have also been observed. However, depending upon Akt phosphorylation status, the mode of apoptosis induction is different [144,145] . KP372-1, a triazinones derivative (Figure 3), inhibits proliferation and induces apoptosis in thyroid cancer, glioblastoma, squamous cell cancer, and acute myelogenous leukemia cell lines [146][147][148][149] .…”

Section: Akt Inhibitorsmentioning

confidence: 99%

PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes

2012

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The PI3K-Akt pathway is a vital regulator of cell proliferation and survival. Alterations in the PIK3CA gene that lead to enhanced PI3K kinase activity have been reported in many human cancer types, including cancers of the colon, breast, brain, liver, stomach and lung. Deregulation of PI3K causes aberrant Akt activity. Therefore targeting this pathway could have implications for cancer treatment. The first generation PI3K-Akt inhibitors were proven to be highly effective with a low IC 50 , but later, they were shown to have toxic side effects and poor pharmacological properties and selectivity. Thus, these inhibitors were only effective in preclinical models. However, derivatives of these first generation inhibitors are much more selective and are quite effective in targeting the PI3K-Akt pathway, either alone or in combination. These second-generation inhibitors are essentially a specific chemical moiety that helps to form a strong hydrogen bond interaction with the PI3K/Akt molecule. The goal of this review is to delineate the current efforts that have been undertaken to inhibit the various components of the PI3K and Akt pathway in different types of cancer both in vitro and in vivo. Our focus here is on these novel therapies and their inhibitory effects that depend upon their chemical nature, as well as their development towards clinical trials.

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Section: Akt Inhibitorsmentioning

confidence: 99%

PI3K and Akt as molecular targets for cancer therapy: current clinical outcomes

2012

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“…Caspases are key mediators of apoptosis, and resistance to apoptosis is considered to be important for the accumulation of CLL cells. Therefore, these results suggest erufosine as a potential drug in CLL patients, and future studies should focus on beneficial approaches for erufosine treatment (Königs et al, 2010).…”

Section: Erufosine and Its Anticancer Propertiesmentioning

confidence: 79%

“…In contrast to most antitumor agents, members of this class can even stimulate the production of hematopoietic progenitor cells. Erufosine, in particular, was shown to be effective against leukemic, multiple myeloma, and oral squamous carcinoma cell lines, as well as against primary chronic lymphocytic leukemia (CLL) cells in vitro, and breast cancer and brain tumors in vivo (Königs et al, 2010;Yosifov et al, 2011;Dineva et al, 2012;Kapoor et al, 2012). It was not toxic to normal hematopoietic progenitor cells of murine or human origin, and even stimulated progenitors from human umbilical cord blood to form granulocyte/macrophage colonies (Yosifov et al, 2011).…”

Section: Erufosine and Its Anticancer Propertiesmentioning

confidence: 99%

“…The ether lipid analogue erufosine (erucylphospho-N,N,N-trimethylpropylammonium; ErPC3; Figure 16.1) is the most recent antineoplastic agent of this group, interfering with signal transduction and conferring apoptosis and autophagy in malignant cells (Königs et al, 2010;Kapoor et al, 2012). Erufosine and its homologue, ErPC, belong to the third generation of the group of APCs.…”

Section: Introductionmentioning

confidence: 99%

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Erufosine Induces Autophagy and Apoptosis in Oral Squamous Cell Carcinoma

Kapoor¹,

Zaharieva²,

Berger³

2014

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

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“…Many recent studies show that several synthetic alkylphosphocholines (edelfosine, miltefosine and perifosine), P-cho analogs, have been developed as a new class of anti-cancer agents. These P-cho analogs act on cellular membranes rather than the DNA, and disturb signal transduction including the inhibition of phosphatidylcholine synthesis, the inhibition of the MAP-kinase/ERK proliferative and phosphatidylinositol 3-kinase/ Akt survival pathways, the stimulation of the Stressactivated protein kinase/JNK cell death pathway, and the inhibition of cell attachment, spreading, and migration (90)(91)(92)(93)(94). P-cho analogs as a class of anti-tumor drugs have been used more and more in clinical studies, but exploring the molecular mechanism of how they interact with cancer cells continues.…”

Section: Car Signaling Regulates Breast Cancer Cell Proliferationmentioning

confidence: 99%