Anti-cancer agents in medicinal chemistry
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Anticancer Agents Med Chem · Jan 2015
ReviewAnticancer Activity of Polyether Ionophore-Salinomycin.
Since the discovery of unusual anti-tumor activity of natural polyether antibiotic - Salinomycin, this compound, along with its derivatives, has been intensively studied against different human cancer cells, both in vivo and in vitro. Salinomycin has shown strong inhibition activity against the proliferation process of many different cancer cells, including multi-drug resistance (MDR) cancer cells, as well as cancer stem cells (CSCs), i.e. leukemic stem cells, colon carcinoma stem cells, prostate cancer stem cells and many others. ⋯ Up to now, major efforts have been devoted to elucidate the biological mechanisms of anti-tumor activity of Salinomycin and it is expected that the results may provide new therapeutic strategies based on biological modulation of Salinomycin activity. This review is focused on and describes the possible role of Salinomycin in cancer therapy and gives an overview of its properties.
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Anticancer Agents Med Chem · Jan 2011
ReviewProtein phosphatase 2A as a potential target for anticancer therapy.
The kinase oncogenes are well-characterized drivers of cancer development, and several targeted therapies focused on both specific and selectively nonselective kinase inhibitors have now been approved for clinical use. In contrast, much less is known about the role of protein phosphatases, although modulation of their activities might form the foundation for an effective anti-cancer approach. ⋯ Recently pharmacological modulation of PP2A activity has been showed to have a potent anti-tumor activity in both in vitro and in vivo cancer models. These studies implicate PP2A as a promising therapeutic target for the treatment of cancer.
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Anticancer Agents Med Chem · May 2014
ReviewLipid rafts, endoplasmic reticulum and mitochondria in the antitumor action of the alkylphospholipid analog edelfosine.
The so-called alkylphospholipid analogs (APLs) constitute a family of synthetic antitumor compounds that target cell membranes. The ether phospholipid edelfosine has been considered the long-standing prototype of these antitumor agents and promotes apoptosis in tumor cells by a rather selective way, while sparing normal cells. Increasing evidence suggests that edelfosine-induced apoptosis involves a number of subcellular structures in tumor cells, including plasma membrane lipid rafts, endoplasmic reticulum (ER) and mitochondria. ⋯ Edelfosine can also interact with mitochondria leading to an increase in mitochondrial membrane permeability and loss of mitochondrial membrane potential. Edelfosine treatment also induced a redistribution of lipid rafts from the plasma membrane to mitochondria, suggesting a raft-mediated link between plasma membrane and mitochondria. The involvement of lipid rafts, ER and mitochondria in the apoptotic response induced by edelfosine may provide new avenues for targeting cancer cells as well as new opportunities for cancer therapy.
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Anticancer Agents Med Chem · Sep 2010
ReviewOvercoming resistance of glioblastoma to conventional cytotoxic therapies by the addition of PARP inhibitors.
This article will present the rationale for combining chemical inhibitors of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP) with conventional cytotoxic agents to improve the treatment of glioblastoma. After a brief review of the current therapeutic options for these aggressive tumours, the possible reasons for their resistance to radiation and chemotherapy will be discussed, highlighting the important role of DNA damage response pathways in many key resistance mechanisms. The dose-limiting toxicities associated with radiation and chemotherapy treatment will be described in order to illustrate the importance of tumour specificity in any attempt to increase the effectiveness of conventional treatments. ⋯ After a brief summary of the key DNA damage response pathways, the biology, biochemistry and pharmacology of PARP and the existing PARP inhibitors will be presented. The major part of the review will cover the effects of combining PARP inhibitors with radiation and chemotherapy in vitro and in vivo, commenting on the underlying mechanisms and indicating where the data are predictive of tumour specific sensitization. Finally, we will consider specific scenarios where PARP inhibitors might contribute to the treatment of glioblastoma patients, discuss the challenges and opportunities associated with early phase clinical testing of these agents, and describe the clinical trials that are either underway or in development.
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Anticancer Agents Med Chem · Nov 2012
ReviewAnti-cancer effects of curcumin on head and neck cancers.
Head and neck cancer is the sixth large type of cancer in the world. The treatment regimens for head and neck cancer encompass surgery, radiotherapy and chemotherapy. However, all current treatment regimens for head and neck cancer have adverse effects. ⋯ This review summarizes the evidence demonstrating potential use of curcumin as a single chemotherapeutic agent or in combination with other chemotherapeutic agents and radiation to minimize their toxicity in head and neck cancer. Although curcumin has been shown to be safe at doses of 8 g/d in both phase I and phase II clinical trials, its bioavailability is poor. Overcoming the poor bioavailability of curcumin in the near future would facilitate its clinical use.