Chemoprevention in hereditary colorectal cancer syndromes

Hawk, M.P.H. Ernest; Ra, Lubet; Limburg, Meike

doi:10.1002/(sici)1097-0142(19991201)86:11+<2551::aid-cncr12>3.0.co;2-1

Cited by 68 publications

(25 citation statements)

References 79 publications

(64 reference statements)

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“…Chemoprevention is a cost-effective alternative to chemotherapy and may offer greater potential in the long run than the use of chemotherapeutic agents (1). Chemoprevention strategies have achieved success in colorectal cancer using nonsteroidal anti-inflammatory drugs (2,3) and breast cancer using tamoxifen (reviewed in Refs. 4,5).…”

mentioning

confidence: 99%

Enhanced Anti-tumor Activity by the Combination of the Natural Compounds (−)-Epigallocatechin-3-gallate and Luteolin

Amin

Wang

Zhang

et al. 2010

Journal of Biological Chemistry

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Natural dietary agents have drawn a great deal of attention toward cancer prevention because of their wide safety margin. However, single agent intervention has failed to bring the expected outcome in clinical trials; therefore, combinations of chemopreventive agents are gaining increasingly popularity. In the present study, we investigated a combinatorial approach using two natural dietary polyphenols, luteolin and EGCG, and found that their combination at low doses (at which single agents induce minimal apoptosis) synergistically increased apoptosis (3-5-fold more than the additive level of apoptosis) in both head and neck and lung cancer cell lines. This combination also significantly inhibited growth of xenografted tumors in nude mice. The in vivo findings also were supported by significant inhibition of Ki-67 expression and increase in TUNEL-positive cells in xenografted tissues. Mechanistic studies revealed that the combination induced mitochondria-dependent apoptosis in some cell lines and mitochondria-independent apoptosis in others. Moreover, we found more efficient stabilization and ATM-dependent Ser 15 phosphorylation of p53 due to DNA damage by the combination, and ablation of p53 using shRNA strongly inhibited apoptosis as evidenced by decreased poly-(ADP-ribose) polymerase and caspase-3 cleavage. In addition, we observed mitochondrial translocation of p53 after treatment with luteolin or the combination of EGCG and luteolin. Taken together, our results for the first time suggest that the combination of luteolin and EGCG has synergistic/additive growth inhibitory effects and provides an important rationale for future chemoprevention trials of head and neck and lung cancers.

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mentioning

confidence: 99%

Enhanced Anti-tumor Activity by the Combination of the Natural Compounds (−)-Epigallocatechin-3-gallate and Luteolin

Amin

Wang

Zhang

et al. 2010

Journal of Biological Chemistry

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“…The efficacy of chemopreventive agents in the colorectum is routinely assessed by measuring one or more end points: biomarker modulation in the at-risk mucosa, adenoma regression, adenoma suppression, or adenoma prevention (25). Our biomarker modulation study evaluated changes in apoptosis and expression of DR4, DR5, h-catenin, and p21 occurring in normal-appearing mucosa following treatment with sulindac in HNPCC and FAP patients.…”

Section: Discussionmentioning

confidence: 99%

Sulindac Inhibits β-Catenin Expression in Normal-Appearing Colon of Hereditary Nonpolyposis Colorectal Cancer and Familial Adenomatous Polyposis Patients

Koornstra¹,

Rijcken²,

Oldenhuis³

et al. 2005

Cancer Epidemiology, Biomarkers &Amp; Prevention

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Sulindac reduces colorectal cancer risk in genetically susceptible humans and animals. The molecular mechanisms underlying these effects are incompletely understood. Many studies suggest an important role for induction of apoptosis involving the mitochondrial pathway and the death receptor pathway. Alternatively, mechanisms involving the APC-B-catenin-Wnt pathway have been suggested, possibly mediated by p21. We determined the effects of sulindac on apoptosis and expression of death receptor (DR)-4 and DR5, B-catenin, and p21 in normal-appearing colorectal epithelium. Biopsies were obtained before and after sulindac treatment during two chemoprevention studies. Patients (n = 18) with hereditary nonpolyposis colorectal cancer (HNPCC) received 150 mg sulindac bd for 4 weeks in a placebo-controlled crossover design. Patients (n = 6) with familial adenomatous polyposis (FAP) received 150 mg sulindac bd for 6 months. Apoptosis was assessed by M30 staining and expression patterns of DR4, DR5, B-catenin, and p21 were studied immunohistochemically. In HNPCC patients, apoptotic indices were similar following placebo and sulindac. Also in FAP patients, apoptotic indices were not different after sulindac compared with pretreatment values. Expression of DR4 and DR5 was observed in all samples with no consistent differences between placebo/ baseline and sulindac. Intensity of membranous B-catenin staining was lower in HNPCC samples following sulindac compared with placebo (P < 0.001). Similar results were obtained in FAP samples (P < 0.01). p21 expressions before and after sulindac treatment were similar in both patient groups. In conclusion, sulindac inhibits B-catenin expression in normal colorectal epithelium from HNPCC and FAP patients without affecting apoptotic indices and DR4, DR5, and p21 expression. (Cancer Epidemiol Biomarkers Prev 2005;14(7):1608 -12)

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“…Mutation of the APC gene has also been observed in 70-80% of sporadic colon cancers (7). Thus, FAP is an ideal model for evaluating the efficacy of surgical and medical treatments for the prevention and regression of colon cancer and adenoma (8).…”

Section: Introductionmentioning

confidence: 99%

“…NSAIDs have been shown to prevent colon cancer in FAP patients as well as the FAP model mice, APC Min-/+ and APC1309 (8,9). However, the long-term ingestion of NSAIDs that is required to inhibit the development of colorectal cancer is frequently associated with adverse side effects, including gastrointestinal irritation and kidney and platelet dysfunction (10,11).…”

Section: Introductionmentioning

confidence: 99%

Prevention of gastrointestinal tumors based on adenomatous polyposis coli gene mutation by dendritic cell vaccine

Iinuma¹,

Homma²,

Noda³

et al. 2004

J. Clin. Invest.

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Chemoprevention in hereditary colorectal cancer syndromes

Cited by 68 publications

References 79 publications

Enhanced Anti-tumor Activity by the Combination of the Natural Compounds (−)-Epigallocatechin-3-gallate and Luteolin

Enhanced Anti-tumor Activity by the Combination of the Natural Compounds (−)-Epigallocatechin-3-gallate and Luteolin

Sulindac Inhibits β-Catenin Expression in Normal-Appearing Colon of Hereditary Nonpolyposis Colorectal Cancer and Familial Adenomatous Polyposis Patients

Prevention of gastrointestinal tumors based on adenomatous polyposis coli gene mutation by dendritic cell vaccine

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