Green Tea Catechins as Novel Antitumor and Antiangiogenic Compounds Pp. 441-463
Michel Demeule,
Jonathan Michaud-Levesque, Borhane Annabi, Denis Gingras, Dominique Boivin,
Julie Jodoin, Sylvie Lamy, Yanick Bertrand, and Richard Béliveau
Rational Design of 5-Aminolevulinic Acid Derivatives Aimed at Improving Photodynamic Therapy Pp. 465-475
Adriana Casas and
Alcira Batlle
Histone Deacetylase Inhibitors and Anticancer Therapy Pp. 477-484
G. Kouraklis and S.
Theocharis
Cytotoxic Anticancer Candidates from Natural Resources Pp. 485-537
Jinwoong Kim and
Novel Concepts in the Development of Platinum Antitumor Drugs Pp. 539-551
M.A. Fuertes, J.
Castilla, C. Alonso and J.M. Pérez
Cross-talk between Cellular Stress, Cell Cycle and Anticancer Agents: Mechanistic Aspects Pp. 553-566
E. Tiligada, V.
Miligkos and A. Delitheos
[Back to top] Green Tea Catechins as Novel Antitumor and Antiangiogenic Compounds
Michel Demeule,
Jonathan Michaud-Levesque, Borhane Annabi, Denis Gingras, Dominique Boivin,
Julie Jodoin, Sylvie Lamy, Yanick Bertrand, and Richard Béliveau
The concept of cancer prevention by use of naturally occuring substances that could be included in the diet is under investigation as a practical approach towards reducing cancer incidence, and therefore the mortality and morbidity associated with this disease. Tea, which is the most popularly consumed beverage aside from water, has been particularly associated with decreased risk of various proliferative diseases such as cancer and atherosclerosis in humans. Various studies have provided evidence that polyphenols are the strongest biologically active agents in green tea. Green tea polyphenols (GTPs) mainly consist of catechins (3-flavanols), of which (-)-epigallocatechin gallate is the most abundant and the most extensively studied. Recent observations have raised the possibility that green tea catechins, in addition to their antioxidative properties, also affect the molecular mechanisms involved in angiogenesis, extracellular matrix degradation, regulation of cell death and multidrug resistance. This article will review the effects and the biological activities of green tea catechins in relation to these mechanisms, each of which plays a crucial role in the development of cancer in humans. The extraction of polyphenols from green tea, as well as their bioavailability, are also discussed since these two important parameters affect blood and tissue levels of the GTPs and consequently their biological activities. In addition, general perspectives on the application of dietary GTPs as novel antiangiogenic and antitumor compounds are also presented.
[Back to top] Rational Design of 5-Aminolevulinic Acid Derivatives Aimed at Improving Photodynamic Therapy
Adriana Casas and
Alcira Batlle
5-aminolevulinic
acid (
[Back to top] Histone Deacetylase Inhibitors and Anticancer Therapy
G. Kouraklis and S.
Theocharis
Recent
reports have shown that pharmacological manipulation of chromatin remodeling by
histone deacetylase (HDAC) inhibitors, might develop into a potent and specific
strategy for the treatment of cancer. Alterations in histone acetylation may
lead to changes in chromatin structure and transcriptional dysregulation of
genes that are implicated in controlling either cell cycle progression or
pathways regulating cell differentiation and/or apoptosis. Dimethyl sulphoxide
was one of the first chemicals to be identified as an inducer of transformed
cell differentiation. In the class of HDAC inhibitors, now included a
short-chain fatty acids, such as 4-phenylbutyrate and valporic acid, hydroxamic
acids, such as suberoylanilide hydroxamic acid (SAHA), pyroxamide, trichostatin
A, oxamflatin and CHAPSs, cyclic tetrapeptides, such as trapoxin, apicidin and
depsipeptide-also known as FK-228 or FR 901228, and benzamides, such as MS-275.
First clinical studies have shown that histone hyperacetylation can be achieved
safely in humans and that treatment of cancer with such agents seems to become
possible. Thus, HDAC inhibitors remains one of the most promising class of new
anticancer agents. Further studies are needed in order to delineate the optimal
dosage, the duration of therapy and possibly the efficacy of other agents able
to synergize with HDAC inhibitors in the fight against cancer.
[Back to top] Cytotoxic Anticancer Candidates from Natural Resources
Jinwoong Kim and
Natural products have been regarded as important sources that could produce potential chemotherapeutic agents. Over 50% of anticancer drugs approved by United States Food and Drug Administration since 1960 were originated from the natural resources, especially from terrestrial plants. Based on cytotoxicity bioassay, over 400 compounds have been isolated from plants, marine organisms and microorganisms from the period of 1996 to 2000. Recently, interest of natural product research has slowly moved to marine organisms. As a result, almost 50% of reported cytotoxic compounds were isolated from marine organisms such as sponges and corals. Also, traditional cytotoxic compounds of acetogenins, alkaloids and terpene skeletons have been reported continuously. In this review, we will present the cytotoxic compounds obtained from natural sources from 1996 to 2000, and the structures and cytotoxic activity of natural compounds isolated from territorial, marine and microorganism resources.
[Back to top] Novel Concepts in the Development of Platinum Antitumor Drugs
M.A. Fuertes, J.
Castilla, C. Alonso and J.M. Pérez
The
limitations of cisplatin as an anticancer drug have stimulated the search for
other antitumor-active platinum complexes with improved pharmacological
properties. The two main goals in the search for new platinum anti-cancer
agents are the reduction of the dose-limiting toxicities of cisplatin and the
circumvention of cisplatin resistance. However, it should be pointed out that
this has proven to be a difficult task. In fact, less than 1% of the thousand
of platinum complexes tested for pre-clinical antitumor activity have entered
clinical trials in the past 30 years. Nonetheless, right now, several new
platinum complexes are in clinical trials, a proof of the continued belief that
platinum complexes may still fulfil the needs for novel antitumor drugs. This
review will focus on the three main innovative approaches found in the platinum
anticancer-field, namely, (1) compounds with decreased reactivity against
nucleophiles, (2) compounds with carrier ligands, and (3) compounds which bind
differently to DNA as compared to cisplatin. In the latter class, special
attention is paid to dinuclear and polinuclear platinum complexes.
[Back to top] Cross-talk between Cellular Stress, Cell Cycle and Anticancer Agents: Mechanistic Aspects
E.
Tiligada, V. Miligkos and A. Delitheos
Environmental conditions such as temperature, radiation, hypoxia, nutrients and drugs stimulate the adaptive sensory and signaling machinery of the cell. This stress response may influence cell cycle regulation, cellular differentiation, oncogenic transforma-tion, cell survival and apoptosis. The impact of the cytoprotective reprogramming in cancer pharmacology is presented by the recent extensive literature regarding the interplay between stress tolerance and anticancer drug effectiveness and resistance, relying on the dominating intrinsic pathways, which are simultaneously activated and regulate the death process either positively or negatively. This review presents the data that argue for the emergence of either common or specific mechanisms depending on the type, duration and severity of stress in all eukaryotic organisms from yeast to mammals. The understanding of the complexity and the balance between noxious and protective signal transduction pathways would contribute to a more explicit evaluation of the current therapeutic regiments and to the development of new leads targeting malignancy.