Antiproliferative effects

Although essential amino acids are requited by both host and tumor, deprivation of select essential amino acids for 2—3 weeks is tolerated by the host yet exerts a pronounced antiproliferative effect on the tumor. Thus, treatment of mice with indole-3-alkane-a-hydroxylase [63363-76-8] from Pseudomonas, which transforms L-tryptophan [73-22-3] to 3-indolylglycaldehyde, lowers the concentration of L-tryptophan in plasma, brain, and lungs, and inhibits the growth of a variety of tumors (32—34). 

Azelaic acid is a naturally occurring dicarboxyl-ic acid (1,7-heptanedicarboxylic acid) that has demonstrated beneficial therapeutic effects in the treatment of acne and several disorders of hyperpigmentation [48]. There are minimal effects on normally pigmented human skin, freckles, senile lentigines, and nevi. The cytotoxic and antiproliferative effects of azelaic acid may be mediated via inhibition of mitochondrial ox-idoreductase activity and DNA synthesis. Disturbance of tyrosinase synthesis by azelaic acid may also influence its therapeutic effects. Azelaic acid can be used as a hypopigmenting agent in patients sensitive to hydroquinone. 

Rapozzi V., Burm B.E.A., CoGOi S., Van DER Marel G.A., Van Boom J.H., Quad-RiFOGLio F., XoDO L. E. Antiproliferative effect in chronic myeloid leukaemia cells by antisense peptide nucleic acids. Nucleic Acids Res. 2002 30 3712-3721. 

Casini, A., Cinellu, M.A., Minghetti, G., Gabbiani, C., Coronnello, M., Mini, E. and Messori, L. (2006) Structural and solution chemistry, antiproliferative effects, and DNA and protein binding properties of a series of dinudear gold(l II) compounds with bipyridyl ligands. Journal of Medicinal Chemistry, 49, 5524. 

Interferon-a2b has diverse mechanisms of action, including antiviral activity, impact on cellular metabolism and differentiation, and antitumor activity.42 The antitumor activity is due to a combination of direct antiproliferative effect on tumor cells and indirect immune-mediated effects.42 Interferon-a2b is currently approved by the Food and Drug Administration (FDA) as adjuvant therapy for patients who are free of disease after curative surgical resection but are at high risk of MM recurrence. This includes patients with bulky disease or regional lymph node involvement such as stage IIB, IIC, or III disease.43 It is controversial if interferon-a2b (IFN) should be offered as adjuvant therapy for every high-risk MM patient. The reason is because clinical trials with different doses of IFN have not proved definitively that IFN improves overall patient survival. 

Interestingly, while it has been reported that the inhibition of cell growth by carotenoids in colon (Palozza et al., 2001b, 2007a) as well as in prostate (Williams et al., 2000) adenocarcinoma cancer cells was independent of p53 and p21 status, HL-60 cells increased their p21 expression as a consequence of the treatment with p-carotene (Palozza et al., 2002b). In addition, the antiproliferative effects of P-carotene required p21 expression in human fibroblasts (Stivala et al., 2000). In contrast, mammary and endometrial cancer cells decreased p21 levels, following lycopene treatment (Nahum et al., 2001). 

In a recent study, LNCaP and PC3 prostate cancer cells treated with lycopene-based agents have been reported to undergo mitotic arrest. Lycopene s antiproliferative effects were likely achieved through a block in Gl/S transition mediated by decreased levels of cyclins D1 and E and cyclin-dependent kinase4 and suppressed retinoblastoma phosphorylation (Ivanov et al., 2007). 

In a recent study, the antiproliferative effect of different carotenoids, including (3-carotene, lycopene and lutein, on PCNA and cyclin Dl expression in human KB cells have been studied. The results indicate that carotenoids suppressed cell growth by acting as inhibitors of the expressions of PCNA and cyclin Dl, although in a different extent (Cheng et al., 2007). On the other hand, (3-carotene was able to induce a cell cycle delay in G2/M phase by decreasing the expression of cyclin A in human colon adenocarcinoma cells (Palozza et al., 2002a). 

Hosokawa, M., Kudo, M., Maeda, H., Kohno, H., Tanaka, T., and Miyashita, K. 2004. Fucoxanthin induces apoptosis and enhances the antiproliferative effect of the PPARgamma ligand, troglitazone, on colon cancer cells. Biochim Biophys Acta 1675 113-119. 

Stivala, L.A., Savio, M., Quarta, S. et al. 2000. The antiproliferative effect of beta-carotene requires p21wafl/ cipl in normal human fibroblasts. Eur J Biochem 267 2290-2296. 

The role of antiproliferative effects of an activated defense reducing the next generation of herbivores compared with the straightforward action of toxins or feeding deterrent metabolites in the evolutionary arms race is still under discussion. The proposed mechanism suggests natural selection at the group level,... 

At cellular level, 6-MP is transformed in a number of active and inactive metabolites, and in the bone marrow, the balance between activation and inactivation of 6-MP is the main determinant of its antiproliferative effect. Similar to other antimetabolites, 6-MP is a prodrug lacking any cytotoxic activity and needs to be activated [3] (Figure 14.1). The first step is 6-MP transformation into 6-thioinosine monophosphate (6-TIMP), which is subsequently converted to 6-thioguanine tri-... 

Several in vitro studies have shown that phenolic compounds in fruits and vegetables have antiproliferative effect in different cancer cell lines (Eberhardt and others 2000 Chu and others 2002 Sun and others 2002 Liu and others 2005 Mertens-Talcott and others 2005 Percival and others 2006). 

Garcia-Solis P, Yahia EM, Morales-Tlalpan V and Diaz-Munoz M. 2009. Screening of antiproliferative effect of aqueous extracts of plant foods in Mexico on the breast cancer cell line MCF-7. Int J Food Sci Nutr. In press. 

In addition to their possible prooxidant activity (see above) polyphenols and flavonoids may influence cancer cells via their antioxidant properties. Recently, Jang et al. [219] studied cancer chemopreventive activity of resveratrol, a natural polyphenolic compound derived from grapes (Chapter 29). These authors showed that resveratrol inhibited the development of preneoplastic lesions in carcinogen-treated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model. Flavonoids silymarin and silibinin also exhibited antitumor-promoting effects at the stage I tumor promotion in mouse skin [220] and manifested antiproliferative effects in rat prostate cancer cells [221]. 

Mycophenolate mofetil (CellCept) inhibits DNA and RNA synthesis and has been shown to have a specific lymphocyte antiproliferative effect. Although not FDA approved for this indication, oral mycophenolate mofetil appears effective in the treatment of moderate to severe plaque psoriasis. The usual dose is 500 mg orally four times a day, up to a maximum of 4 g/day. Common adverse effects include GI toxicity (diarrhea, nausea, vomiting), hematologic effects (anemia, neutropenia, thrombocytopenia), and viral and bacterial infections. Lymphoproliferative disease or lymphoma has been reported. 

There are evidences showing that lower daily doses of tamoxifen, between 1 and 5 mg, can obtain antiproliferative effects on in situ or small invasive cancers similar to those observed with the usual dose of 20 mg (Decensi et al. 2003). If that proves to be true with respect to the protective effect in primary prevention, it would probably allow skipping the negative effects on endometrium and coagulation, both dose related. 

Arzoxifene is an orally active third-generation selective ER modulator. Arzoxifene has been shown to induce apoptosis in an ER-positive cell fine through a mechanism that includes induction of TGF)6 (Colletta et al. 1990). The capacity to induce TGF-/ expression may contribute to the potential antiproliferative effects of arzoxifene in hormonally responsive uterine. 

The antiproliferative effects of arsenic are well documented. In vitro both divalent and pentavalent arsenicals inhibit murine [28] and bovine [18] phytohemaglutinin (PHA)-stimulated lymphoproliferation at concentrations of > 3 pM. Lymph node cells from arsenic treated, FTTC-sensitized mice displayed reduced lymphoproliferation in response to Con A, suggesting that the mechanism of antigen processing/presentation may be altered by arsenic exposure, inhibiting T-cell responsiveness [29], However, in vivo... 

In 1965 Rosenberg et al. (8, 9) accidentally discovered the antiproliferative effect of cis-diammine platinum complexes, which led to the first clinical trials of cis-[PtCl2(NH3)2] 1 in 1971 and resulted in the clinical use of cisplatin worldwide. Cisplatin and carboplatin 2 are the most widely used anticancer drugs, and two other analogs, nedaplatin 3 and oxaliplatin 4 (chiral centers indicated), have recently been approved for clinical use in Japan and France, respectively. 

The in vivo antitumor effects of interferons are believed to be related to both augmentation of natural killer cell activity and antiproliferative effects. Antiproliferative activity probably also accounts for the bone marrow suppression observed in some individuals given IFN and could potentially produce effects in a routine preclinical reproduction or teratology evaluation. Dosing studies performed in... 

Unnecessary animal testing can be avoided by relying on in vitro studies as the first stage acute toxicity and cytocompatibility test for injectable materials (Pearce et al., 2007). Many researchers have utilized in vitro studies to screen the cellular response to CNTs (Raja et al., 2007) and to investigate the various CNT-mammalian cell interactions such as oxidative stress (Manna et al., 2005 Shvedova et al., 2003, 2007), antiproliferative effects (Cui et al., 2005 Garibaldi et al., 2006), decreased cell adhesion (Cui et al., 2005), apoptosis (Bottini et al., 2006 Cui et al., 2005 Jia et al., 2005), and necrosis (Jia et al., 2005). A summary of these in vitro studies are presented in Table 12.1. 

Antiproliferative Effects of Phenolic Compounds Isolated from Brazilian Propolis... 

Several compounds have been isolated from propolis and among them, kaempferide has been reported to have several pharmaceutical functions, including melanogenesis inhibitor [15], antioxidant [16], and hypertension modulator [17], However, whether treatment of carcinoma cells with kaempferide has an antiproliferative effect is unclear as cancer study of it is rare until now. 

In this study, we isolated single compounds from propolis and determined whether they had an antiproliferative effect against carcinoma cells. 

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