Leukemias resveratrol

Classic antioxidants, vitamin E, vitamin C, and others can suppress the activation of apoptosis. For example, ascorbic acid prevented cytochrome c release and caspase activation in human leukemia cells exposed to hydrogen peroxide [128], Pretreatment with A -acctylcystcinc, ascorbate, and vitamin E decreased homocysteine thiolactone-induced apoptosis in human promyelocytic leukemia HL-60 cells [129]. Resveratrol protected rat brain mitochondria from anoxia-reoxygenation damage by the inhibition of cytochrome c release and the reduction of superoxide production [130]. However, it should be mentioned that the proapoptotic effect of ascorbate, gallic acid, or epigallocatechin gallate has been shown in the same human promyelocytic leukemia cells [131]. 

Mertens-Talcott SU, Percival SS. Ellagic acid and quercetin interact synergis-tically with resveratrol in the induction of apoptosis and cause transient cell cycle arrest in human leukemia cells. Cancer Lett 2005 218(2) 141-151. 

The diet consists of varied ingredients that impart their potential benefits to human health. Potential interaction of resveratrol with other constituents of the diet is worth considering. Resveratrol has been shown to synergize with both quercetin and ellagic acid present in most of our natural products, in the induction of apoptosis in human leukemia cells [Mertens-Talcott and Percival... 

Dorrie J, Gerauer H, Wachter Y, Zunino SJ. 2001. Resveratrol induces extensive apoptosis by depolarizing mitochondrial membranes and activating caspase-9 in acute lymphoblastic leukemia cells. Cancer Res 61 4731-4739. 

The expression of iNOS and the generation of NO in LPS-activated RAW 264.7 cells were inhibited by resveratrol [Murakami et al., 2003 Tsai et al., 1999], The compound significantly diminished the expression of tumor necrosis factor (TNF)-o mRNA in LPS-activated J774.2 macrophage cells [Kowalski et al., 2005] and peripheral blood leukocytes [Richard et al., 2005]. The expression of interleukin (IL)-8 protein and/or its mRNA in human monocytic leukemia (U937) cells [Shen et al., 2003] and human peripheral blood... 

Estrov Z, Shishodia S, Faderl S, Harris D, Van Q, Kantarjian HM, Talpaz M, Aggarwal BB. 2003. Resveratrol blocks interleukin-1 beta-induced activation of the nuclear transcription factor NF-kB, inhibits proliferation, causes S-phase arrest, and induces apoptosis of acute myeloid leukemia cells. Blood 102 987-995. 

Li T, Fan GX, Wang W, Yuan YK. 2007. Resveratrol induces apoptosis, influences IL-6 and exerts immunomodulatory effect on mouse lymphocytic leukemia both in vitro and in vivo. Int Immtmopharmacol 7 1221-1231. 

Bernhard, D., Schwaiger, W., Crazzolara, R., Tinhofer, I., Kofler, R, Be Csordas, A (2003). Enhanced MTT-reducing activity under growth inhibition by resveratrol in CEM-C7H2 lymphocytic leukemia cells. Cancer Letters, 195, 193—199. 

Low levels (0.1-1 pg/mL) of resveratrol have been reported to enhance cell proliferation, whereas higher amounts (10-100 pg/mL) cause apoptosis in a vari-ety of tumor and endothelial cells, including JB6 epidermal cells, human promyeloctye leukemia HL-60 cells, THP-1 human monocytic leukemia cells, U937 human promonocytic cells, various colon cancer cell lines, human mammary cancer cell lines, and human prostate cancer cells [121-131]. In somewhat of a contrast to these studies, a very recent report indicated that resveratrol reduced paclitaxel-induced apoptosis in a human neuroblastoma cell line (SH-SY5Y) by blocking paclitaxel-induced phosphorylation of JNKs, Raf-1, and BcT2 [132]. Of particular interest is a recent study in which it was shown to induce apoptosis in leukemic human lymphocytes but, under similar conditions, had no effect on the survival... 

Resveratrol has been shown to inhibit proliferation, induce differentiation, and enhance the expression of adhesion molecules (GDI la, GDI lb, GDIS, GD54) in a variety of myeloid leukemia cell lines [144]. The inhibitory effect of resveratrol on cell survival and proliferation of human breast cancer cells was shown to be estrogen receptor dependent [145]. Other studies indicated that it was very effective in inhibiting growth of 4T1 breast cancer cells in culture but had little effect on 4T1 tumor cell growth in mice [146]. In stark contrast, resveratrol was tested against mammary tumors induced by 7, 12-dimethylbenz(a)anthracene (DMBA) in rats [147]. In this case, reductions in incidence, multiplicity, and latency period of tumor development were observed. Additional... 

Surh YJ, Hurh YJ, Kang JY, Lee E, Kong G, Lee SJ. Resveratrol, an antioxidant present in red wine, induces apoptosis in human promyelocytic leukemia (HL-60) cells. Cancer Lett 1999 140 1-10. 

Tsan MF, White JE, Maheshwari JG, Chikkappa G. Anti-leukemia effect of resveratrol. Leuk Lymphoma 2002 43 983-987. 

Billard C, Izard JC, Roman V, Kern C, Mathiot C, Mentz E, Kolb JP. Comparative antiproliferative and apoptotic effects of resveratrol, epsUon-vintferin and vineshols derived polyphenols (vineatrols) on chronic B lymphocytic leukemia cells and normal human lymphocytes. Leuk Lymphoma 2002 43 1991-2002. 

Bernhard D, Tinhofer I, Tonko M, Hubl H, Ausserlechner MJ, Greil R, Kofler R, Csordas A. Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia cells. Cell Death Differ 2000 7 834-842. 

Asou H, Koshizuka K, Kyo T, Takata N, Kamada N, Koeffier HP. Resveratrol, a natural product derived from grapes, is a new inducer of differentiation in human myeloid leukemias. Int J Hematol 2002 75 528-533. 

Promotion of cellular differentiation is a promising postulated mechanism for chemoprevention. Several compounds have been reported to induce cell differentiation, including retinoids, vitamin D3, and genistein. " Resveratrol is capable of inducting differentiation in some hematological malignant cell lines, colon cancers, and neuroblastoma. Jang et al. reported that incubation of the promyelocytic leukemia HL-60 cells with resveratrol induces cell differentiation and reduction of DNA synthesis. 

Resveratrol has been reported to inhibit all three stages of carcinogenesis initiation, progression, and promotion in several types of cancer. Several reports suggested that resveratrol inhibits cancer initiation in various model systems. Sharma et al. found that resveratrol reduced 12-0-tetradecanoylphorbol-13-acetate (TPA)-induced free-radical formation in human promyelocytic leukemia cells HL-60. In another model, resveratrol also inhibited 7,12-dimethylbenzfi3)anthracene (DMBA)-induced preneoplastic lesion in... 

Quiney C, Dauzonne D, Kem C, Foumeron ID, Izard JC, Mt ammad RM, Kolb JP, Billard C (2004) Havones and polyphenols inhibit the NO pathway during apoptosis of leukemia B-cells. Leuk Res 28 851-861 Ragione FD, Cucciolla V, BarieHo A, Pietra VD, Racioppi L, Soldati G, Manna C, GaUetti P, Zappia V (1998) Resveratrol arrests the cell division cycle at S/G2 phase transition. Biochem Bio[4iys Res Com-... 

Resveratrol (grape, red wine) HL-60 human leukemia cell line, SHEP neuroblastoma cells Release of cytochrome c from mitochondria, activation of caspases, induction of p53-dependent transcriptional activation sensitizes TRAIL-induced apoptosis decreases in survivin, increases in Smac/DIABLO [155,156]... 

Documented effects The alkaloid spherophysine, which was isolated from the aboveground plant parts, has hypotensive activity and effects uterine action. In the form of a benzoic-acid salt, it is used for essential hypertension of the first and second degrees. Spherophysine is used for arterial hypertension, weak birthing activity (labor difficulties), and post natal bleeding (Sokolov and Zamotaev 1989). A stilbene isolated from the plant was synthesized and tested for antioxidant activity and showed superior antioxidative activity when compared to the well-known antioxidants resveratrol, vitamin C and butylated hydroxyanisole (BHA) (Venkateswarlu et al. 2003). Additionally, synthesized stilbenes based on naturally occurring compounds were active against leukemia and lymphoma cell lines (Tolomeo et al. 2005). 

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