H-H. Sherry Chow
- Research Scientist, Cancer Center Division
- Research Professor, Medicine
- Research Professor, Pharmaceutical Sciences
- Research Professor, Clinical Translational Sciences
- Sidney E. Salmon Distinguished Investigator Award
- UACC, Spring 2017
No activities entered.
DissertationCTS 920 (Spring 2021)
DissertationCBIO 920 (Fall 2020)
DissertationCTS 920 (Fall 2020)
DissertationCBIO 920 (Spring 2020)
ResearchCTS 900 (Spring 2020)
DissertationCBIO 920 (Fall 2019)
Research ConferenceCBIO 695A (Fall 2019)
DissertationCBIO 920 (Spring 2019)
ResearchCTS 900 (Spring 2019)
Research ConferenceCBIO 695A (Spring 2019)
DissertationCBIO 920 (Fall 2018)
Research ConferenceCBIO 695A (Fall 2018)
Directed RsrchMCB 492 (Summer I 2018)
DissertationCBIO 920 (Spring 2018)
Research ConferenceCBIO 695A (Spring 2018)
DissertationCBIO 920 (Fall 2017)
Research ConferenceCBIO 695A (Fall 2017)
DissertationCBIO 920 (Spring 2017)
Research ConferenceCBIO 695A (Spring 2017)
DissertationCBIO 920 (Fall 2016)
Research ConferenceCBIO 695A (Fall 2016)
DissertationCBIO 920 (Spring 2016)
ResearchCBIO 900 (Spring 2016)
Research ConferenceCBIO 695A (Spring 2016)
- Batai, K., Trejo, M. J., Chen, Y., Kohler, L. N., Lance, P., Ellis, N. A., Cornelis, M. C., Chow, H. S., Hsu, C. H., & Jacobs, E. T. (2020). Genome-Wide Association Study of Response to Selenium Supplementation and Circulating Selenium Concentrations in Adults of European Descent. The Journal of nutrition.More infoSelenium (Se) is a trace element that has been linked to many health conditions. Genome-wide association studies (GWAS) have identified variants for blood and toenail Se levels, but no GWAS has been conducted to date on responses to Se supplementation.
- Kunihiro, A. G., Luis, P. B., Frye, J. B., Chew, W., Chow, H. H., Schneider, C., & Funk, J. L. (2020). Bone-Specific Metabolism of Dietary Polyphenols in Resorptive Bone Diseases. Molecular nutrition & food research, 64(14), e2000072.More infoCurcumin prevents bone loss in resorptive bone diseases and inhibits osteoclast formation, a key process driving bone loss. Curcumin circulates as an inactive glucuronide that can be deconjugated in situ by bone's high β-glucuronidase (GUSB) content, forming the active aglycone. Because curcumin is a common remedy for musculoskeletal disease, effects of microenvironmental changes consequent to skeletal development or disease on bone curcumin metabolism are explored.
- Garland, L. L., Guillen-Rodriguez, J., Hsu, C. H., Yozwiak, M., Zhang, H. H., Alberts, D. S., Davis, L. E., Szabo, E., Merenstein, C., Lel, J., Zhang, X., Liu, H., Liu, G., Spira, A. E., Beane, J. E., Wojtowicz, M., & Chow, H. S. (2019). Effect of Intermittent Versus Continuous Low-Dose Aspirin on Nasal Epithelium Gene Expression in Current Smokers: A Randomized, Double-Blinded Trial. Cancer prevention research (Philadelphia, Pa.), 12(11), 809-820.More infoA chemopreventive effect of aspirin (ASA) on lung cancer risk is supported by epidemiologic and preclinical studies. We conducted a randomized, double-blinded study in current heavy smokers to compare modulating effects of intermittent versus continuous low-dose ASA on nasal epithelium gene expression and arachidonic acid (ARA) metabolism. Fifty-four participants were randomized to intermittent (ASA 81 mg daily for one week/placebo for one week) or continuous (ASA 81 mg daily) for 12 weeks. Low-dose ASA suppressed urinary prostaglandin E2 metabolite (PGEM; change of -4.55 ± 11.52 from baseline 15.44 ± 13.79 ng/mg creatinine for arms combined, = 0.02), a surrogate of COX-mediated ARA metabolism, but had minimal effects on nasal gene expression of nasal or bronchial gene-expression signatures associated with smoking, lung cancer, and chronic obstructive pulmonary disease. Suppression of urinary PGEM correlated with favorable changes in a smoking-associated gene signature ( < 0.01). Gene set enrichment analysis (GSEA) showed that ASA intervention led to 1,079 enriched gene sets from the Canonical Pathways within the Molecular Signatures Database. In conclusion, low-dose ASA had minimal effects on known carcinogenesis gene signatures in nasal epithelium of current smokers but results in wide-ranging genomic changes in the nasal epithelium, demonstrating utility of nasal brushings as a surrogate to measure gene-expression responses to chemoprevention. PGEM may serve as a marker for smoking-associated gene-expression changes and systemic inflammation. Future studies should focus on NSAIDs or agent combinations with broader inhibition of pro-inflammatory ARA metabolism to shift gene signatures in an anti-carcinogenic direction.
- Jacobs, E. T., Lance, P., Mandarino, L. J., Ellis, N. A., Chow, H. S., Foote, J., Martinez, J. A., Hsu, C. P., Batai, K., Saboda, K., & Thompson, P. A. (2019). Selenium supplementation and insulin resistance in a randomized, clinical trial. BMJ open diabetes research & care, 7(1), e000613.More infoWhile controversial, observational and randomized clinical trial data implicate the micronutrient selenium (Se) in the development of type 2 diabetes (T2D). The aim of this study was to test the hypothesis that Se supplementation adversely affects pancreatic β-cell function and insulin sensitivity.
- Kunihiro, A. G., Luis, P. B., Brickey, J. A., Frye, J. B., Chow, H. S., Schneider, C., & Funk, J. L. (2019). Beta-Glucuronidase Catalyzes Deconjugation and Activation of Curcumin-Glucuronide in Bone. Journal of natural products, 82(3), 500-509.More infoThe biological basis for documented in vivo bone-protective effects of turmeric-derived curcumin is unclear since curcumin is barely detectable in serum, being rapidly conjugated to form what is thought to be an inactive glucuronide. Studies were therefore undertaken to test the postulate that antiresorptive effects of curcumin require deconjugation within bone to form the bioactive aglycone and that β-glucuronidase (GUSB), a deconjugating enzyme expressed by hematopoietic marrow cells, facilitates this site-specific transformation. Consistent with this postulate, aglycone, but not glucuronidated, curcumin inhibited RANKL-stimulated osteoclastogenesis, a key curcumin target in bone. Aglycone curcumin, expressed relative to total curcumin, was higher in bone marrow than in serum of curcumin-treated C57BL/6J mice, while remaining a minor component. Ex vivo, under conditions preventing further metabolism of the unstable aglycone, the majority of curcumin-glucuronide delivered to marrow in vivo was hydrolyzed to the aglycone, a process that was inhibited by treatment with saccharolactone, a GUSB inhibitor, or in mice having reduced (C3H/HeJ) or absent (mps/mps) GUSB activity. These findings suggest that curcumin, despite low systemic bioavailability, may be enzymatically activated (deconjugated) within GUSB-enriched bone to exert protective effects, a metabolic process that could also contribute to bone-protective effects of other highly glucuronidated dietary polyphenols.
- Song, J. H., Kang, H. J., Luevano, L. A., Gokhale, V., Wu, K., Pandey, R., Sherry Chow, H. H., Hurley, L. H., & Kraft, A. S. (2019). Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death. Cell chemical biology, 26(8), 1110-1121.e4.More infoIncreased telomerase activity is associated with malignancy and poor prognosis in human cancer, but the development of targeted agents has not yet provided clinical benefit. Here we report that, instead of targeting the telomerase enzyme directly, small molecules that bind to the G-hairpin of the hTERT G-quadruplex-forming sequence kill selectively malignant cells without altering the function of normal cells. RG260 targets the hTERT G-quadruplex stem-loop folding but not tetrad DNAs, leading to downregulation of hTERT expression. To improve physicochemical and pharmacokinetic properties, we derived a small-molecule analog, RG1603, from the parent compound. RG1603 induces mitochondrial defects including PGC1α and NRF2 inhibition and increases oxidative stress, followed by DNA damage and apoptosis. RG1603 injected as a single agent has tolerable toxicity while achieving strong anticancer efficacy in a tumor xenograft mouse model. These results demonstrate a unique approach to inhibiting the hTERT that functions by impairing mitochondrial activity, inducing cell death.
- Zeng, Y., Moscicki, A. B., Sahasrabuddhe, V. V., Garcia, F., Woo, H., Hsu, C. H., Szabo, E., Dimond, E., Vanzzini, S., Mondragon, A., Butler, V., DeRose, H., & Chow, H. S. (2019). A prospective, single-arm, open-label, non-randomized, phase IIa trial of a nonavalent prophylactic HPV vaccine to assess immunogenicity of a prime and deferred-booster dosing schedule among 9-11 year-old girls and boys - clinical protocol. BMC cancer, 19(1), 290.More infoHuman papillomavirus (HPV) vaccines are indicated for the prevention of cancers and genital warts caused by vaccine-covered HPV types. Although the standard regimen requires a two or three-dose vaccine series, there is emerging data suggesting that a single dose of the bivalent or quadrivalent HPV vaccine generates persistently positive antibody titers. No similar data is yet available for the nonavalent HPV vaccine, currently the only HPV vaccine available in the United States. The overall objective of our study is to assess the stability and kinetics of antibody titers for 24 months following a single dose of the nonavalent HPV vaccine among preteen girls and boys.
- Chow, H. (2018). Effects of Black and Green Tea Consumption on Blood Pressure and Liver Enzymes: A Randomized Controlled Trial. J Nutr Food Sci, 8, 661. doi:10.4172/2155-9600.1000661
- Kohler, L. N., Florea, A., Kelley, C. P., Chow, S., Hsu, P., Batai, K., Saboda, K., Lance, P., & Jacobs, E. T. (2018). Higher Plasma Selenium Concentrations Are Associated with Increased Odds of Prevalent Type 2 Diabetes. The Journal of nutrition, 148(8), 1333-1340.More infoSelenium, an essential trace element, has been investigated as a potential cancer prevention agent. However, several studies have indicated that selenium supplementation may be associated with an increased risk of type 2 diabetes (T2D), although an equivocal relation of this nature requires confirmation.
- Kohler, L. N., Foote, J., Kelley, C. P., Florea, A., Shelly, C., Chow, H. S., Hsu, P., Batai, K., Ellis, N., Saboda, K., Lance, P., & Jacobs, E. T. (2018). Selenium and Type 2 Diabetes: Systematic Review. Nutrients, 10(12).More infoSeveral studies have investigated the potential role of selenium (Se) in the development of type 2 diabetes (T2D) with disparate findings. We conducted a systematic review and meta-analysis to synthesize the evidence of any association between Se and T2D. PubMed, Embase, and Scopus were searched following the Preferred Reporting Items for Systematic Reviews and Meta-analysis Approach (PRISMA). Sixteen studies from 15 papers met inclusion criteria defined for this review. Of the 13 observational studies included, 8 demonstrated a statistically significant positive association between concentrations of Se and odds for T2D, with odds ratios (95% confidence intervals) ranging from 1.52 (1.01⁻2.28) to 7.64 (3.34⁻17.46), and a summary odds ratio (OR) (95% confidence interval (CI)) of 2.03 (1.51⁻2.72). In contrast, among randomized clinical trials (RCTs) of Se, a higher risk of T2D was not observed for those who received Se compared to a placebo (OR = 1.18, 95% CI 0.95⁻1.47). Taken together, the results for the relationship between Se and T2D differ between observational studies and randomized clinical trials (RCTs). It remains unclear whether these differences are the result of uncontrolled confounding in the observational studies, or whether there is a modest effect of Se on the risk for T2D that may vary by duration of exposure. Further investigations on the effects of Se on glucose metabolism are needed.
- Nguyen, M. M., Martinez, J. A., Hsu, C. H., Sokoloff, M., Krouse, R. S., Gibson, B. A., Nagle, R. B., Parnes, H. L., Cordova, C., & Chow, H. S. (2018). Bioactivity and prostate tissue distribution of metformin in a preprostatectomy prostate cancer cohort. European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP), 27(6), 557-562.More infoMetformin has recently been shown to have potential to reduce prostate cancer risk. We conducted a randomized, double-blind, placebo-controlled trial to determine the modulating effects of metformin on tissue and systemic biomarkers of drug activity and its distribution into the prostate tissue. Twenty patients with prostate cancer scheduled to undergo prostatectomy were randomly assigned to receive either extended-release metformin or placebo for a median of 34 days before surgery. Prostatectomy and serum samples were analyzed for metformin concentrations, serum biomarkers of drug activity (prostate-specific antigen, insulin, insulin-like growth factor-1, insulin-like growth factor binding protein 3, sex hormone-binding globulin, and testosterone) and tissue biomarkers of proliferation, apoptosis, cell cycle regulation, and mTOR inhibition. For participants in the metformin arm, the prostate tissue and serum metformin concentrations ranged from 0.88 to 51.2 μg/g tissue and from not detectable to 3.6 μg/ml, respectively. There were no differences between the two groups in either the postintervention tissue biomarker expression in the prostatectomy tissue or pre to postintervention changes in serum biomarkers. We conclude that metformin distributes to human prostate tissue, suggesting that metformin could exert its effects directly on tissue targets. However, there was no difference in tissue and systemic drug effect biomarkers between the two treatment arms. Future studies with longer intervention duration and larger sample size should be considered in order to evaluate the potential of metformin for prostate cancer prevention.
- Parsons, J. K., Pinto, P. A., Pavlovich, C. P., Uchio, E., Kim, H. L., Nguyen, M. N., Gulley, J. L., Jamieson, C., Hsu, P., Wojtowicz, M., Parnes, H., Schlom, J., Dahut, W. L., Madan, R. A., Donahue, R. N., & Chow, H. S. (2018). A Randomized, Double-blind, Phase II Trial of PSA-TRICOM (PROSTVAC) in Patients with Localized Prostate Cancer: The Immunotherapy to Prevent Progression on Active Surveillance Study. European urology focus, 4(5), 636-638.More infoThe Immunotherapy to Prevent Progression on Active Surveillance Study is the first trial of immunotherapy for localized prostate cancer. We randomized active surveillance patients to PSA-TRICOM (PROSTVAC) or placebo for 5mo. Final results will be available in 2019.
- Chow, H. (2017). Modulation of oxidative damage by green and black tea: role of smoking and gender in a randomized trial. J Nutr Food Sci, 7, 633. doi:10.4172/2155-9600.1000633
- Gattoc, L., Frew, P. M., Thomas, S. N., Easley, K. A., Ward, L., Chow, H. S., Ura, C. A., & Flowers, L. (2017). Phase I dose-escalation trial of intravaginal curcumin in women for cervical dysplasia. Open access journal of clinical trials, 9, 1-10.More infoThis is a Phase I trial demonstrating safety and tolerability of intravaginal curcumin for future use in women with cervical neoplasia.
- Guthrie, A. R., Chow, H. S., & Martinez, J. A. (2017). Effects of resveratrol on drug- and carcinogen-metabolizing enzymes, implications for cancer prevention. Pharmacology research & perspectives, 5(1), e00294.More infoResveratrol is a polyphenol found in grape skins and peanuts that has demonstrated many health benefits including protection against aging, cardiovascular and metabolic disease, neurological decline, and cancer. The anticancer properties of resveratrol have been attributed to a variety of mechanisms, including its general inhibition of phase I metabolism and induction of phase II metabolism. The effects of resveratrol on these enzymes, however, are still unclear, as in vitro evidence often contrasts with animal studies and clinical trials. Reasons for these variances could include the low bioavailability of resveratrol and the effects of resveratrol metabolites. Due to resveratrol's interactions with drug-metabolizing enzymes and drug transporters, individuals concurrently taking pharmacological doses of resveratrol with other supplements or medications could potentially experience nutrient-drug interactions. This review summarizes the known effects of resveratrol and its main metabolites on drug metabolism in order to help characterize which populations might benefit from resveratrol for the prevention of cancer, as well as those that may need to avoid supplementation due to potential drug interactions.
- Thomson, C. A., Chow, H. H., Wertheim, B. C., Roe, D. J., Stopeck, A., Maskarinec, G., Altbach, M., Chalasani, P., Huang, C., Strom, M. B., Galons, J. P., & Thompson, P. A. (2017). A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast cancer research and treatment, 165(1), 97-107.More infoDiindolylmethane (DIM), a bioactive metabolite of indole-3-carbinol found in cruciferous vegetables, has proposed cancer chemoprevention activity in the breast. There is limited evidence of clinically relevant activity of DIM or long-term safety data of its regular use. A randomized, double-blind, placebo-controlled trial was conducted to determine the activity and safety of combined use of BioResponse DIM® (BR-DIM) with tamoxifen.
- Banerjee, B., Shaheen, N. J., Martinez, J. A., Hsu, C., Trowers, E., Gibson, B. A., Della'Zanna, G., Richmond, E., & Chow, H. S. (2016). Clinical Study of Ursodeoxycholic Acid in Barrett's Esophagus Patients. Cancer prevention research (Philadelphia, Pa.), 9(7), 528-33.More infoPrior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett's esophagus and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with Barrett's esophagus. Twenty-nine patients with Barrett's esophagus received UDCA treatment at a daily dose of 13 to 15 mg/kg/day for 6 months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine), cell proliferation (Ki67), and apoptosis (cleaved caspase-3) in Barrett's esophagus epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography/mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. After UDCA intervention, UDCA increased significantly to account for 93.4% of total gastric bile acids (P < 0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the Barrett's esophagus biopsies by IHC. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high-dose UDCA supplementation for 6 months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the Barrett's esophagus epithelium. Cancer Prev Res; 9(7); 528-33. ©2016 AACRSee related article by Brian J. Reid, p. 512.
- López, A. M., Pruthi, S., Boughey, J. C., Perloff, M., Hsu, C., Lang, J. E., Ley, M., Frank, D., Taverna, J. A., & Chow, H. S. (2016). Double-Blind, Randomized Trial of Alternative Letrozole Dosing Regimens in Postmenopausal Women with Increased Breast Cancer Risk. Cancer prevention research (Philadelphia, Pa.), 9(2), 142-8.More infoAromatase inhibitors (AI) profoundly suppress estrogen levels in postmenopausal women and are effective in breast cancer prevention among high-risk postmenopausal women. Unfortunately, AI treatment is associated with undesirable side effects that limit patient acceptance for primary prevention of breast cancer. A double-blind, randomized trial was conducted to determine whether low and intermittent doses of letrozole can achieve effective estrogen suppression with a more favorable side-effect profile. Overall, 112 postmenopausal women at increased risk for breast cancer were randomized to receive letrozole at 2.5 mg once daily (QD, standard dose arm), 2.5 mg every Monday, Wednesday, and Friday (Q-MWF), 1.0 mg Q-MWF, or 0.25 mg Q-MWF for 24 weeks. Primary endpoint was suppression in serum estradiol levels at the end of letrozole intervention. Secondary endpoints included changes in serum estrone, testosterone, C-telopeptide (marker of bone resorption), lipid profile, and quality-of-life measures (QoL) following treatment. Significant estrogen suppression was observed in all dose arms with an average of 75% to 78% and 86% to 93% reduction in serum estradiol and estrone levels, respectively. There were no differences among dose arms with respect to changes in C-telopeptide levels, lipid profile, adverse events (AE), or QoL measures. We conclude that low and intermittent doses of letrozole are not inferior to standard dose in estrogen suppression and resulted in a similar side-effect profile compared with standard dose. Further studies are needed to determine the feasibility of selecting an effective AI dosing schedule with better tolerability. Cancer Prev Res; 9(2); 142-8. ©2015 AACR.
- Martinez, J. A., Chalasani, P., Thomson, C. A., Roe, D., Altbach, M., Galons, J., Stopeck, A., Thompson, P. A., Villa-Guillen, D. E., & Chow, H. S. (2016). Phase II study of metformin for reduction of obesity-associated breast cancer risk: a randomized controlled trial protocol. BMC cancer, 16, 500.More infoTwo-thirds of U.S. adult women are overweight or obese. High body mass index (BMI) and adult weight gain are risk factors for a number of chronic diseases, including postmenopausal breast cancer. The higher postmenopausal breast cancer risk in women with elevated BMI is likely to be attributable to related metabolic disturbances including altered circulating sex steroid hormones and adipokines, elevated pro-inflammatory cytokines, and insulin resistance. Metformin is a widely used antidiabetic drug that has demonstrated favorable effects on metabolic disturbances and as such may lead to lower breast cancer risk in obese women. Further, the anti-proliferative effects of metformin suggest it may decrease breast density, an accepted biomarker of breast cancer risk.
- Thompson, P. A., Ashbeck, E. L., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., Bhattacharyya, A., Hsu, C., Chow, H. H., Ahnen, D. J., Boland, C. R., Heigh, R. I., Fay, D. E., Hamilton, S. R., Jacobs, E. T., Martinez, M. E., Alberts, D. S., & Lance, P. (2016). Selenium Supplementation for Prevention of Colorectal Adenomas and Risk of Associated Type 2 Diabetes. Journal of the National Cancer Institute, 108(12).More infoSelenium supplementation may help to prevent colorectal cancer; as precursors of colorectal cancer, colorectal adenomas are a surrogate for colorectal cancer. Selenium supplementation may increase risk of type 2 diabetes (T2D).
- Thompson, P. A., Ashbeck, E. L., Roe, D. J., Fales, L., Buckmeier, J., Wang, F., Bhattacharyya, A., Hsu, C., Chow, S. H., Ahnen, D. J., Boland, C. R., Heigh, R. I., Fay, D. E., Hamilton, S. R., Jacobs, E. T., Martinez, E. M., Alberts, D. S., & Lance, P. (2016). Celecoxib for the Prevention of Colorectal Adenomas: Results of a Suspended Randomized Controlled Trial. Journal of the National Cancer Institute, 108(12).More infoCyclooxygenase (COX)-2 inhibitors such as celecoxib were designed to preserve anti-inflammatory activity without inhibiting COX-1. Downregulation of COX-2 inhibits colorectal carcinogenesis.
- Aldaham, S., Foote, J. A., Chow, H. S., & Hakim, I. A. (2015). Smoking status effect on inflammatory markers in a randomized trial of current and former heavy smokers. International Journal of Inflammation, 2015, 6 pages. doi:10.1155/2015/439396
- Curiel-Lewandrowski, C., Tang, J. Y., Einspahr, J. G., Bermudez, Y., Hsu, C. H., Rezaee, M., Lee, A. H., Tangrea, J., Parnes, H. L., Alberts, D. S., & Chow, H. S. (2015). Pilot study on the bioactivity of vitamin d in the skin after oral supplementation. Cancer prevention research (Philadelphia, Pa.), 8(6), 563-9.More infoLaboratory studies suggest that vitamin D (VD) supplementation inhibits skin carcinogenesis. However, epidemiologic studies report mixed findings in the association between circulating VD levels and skin cancer risk. We conducted a clinical study to determine whether oral cholecalciferol supplementation would exert direct bioactivity in human skin through modulation of the VD receptor (VDR). We enrolled 25 individuals with serum 25-hydroxyvitamin-D levels
- Miller, J. A., Pappan, K., Thompson, P. A., Want, E. J., Siskos, A. P., Keun, H. C., Wulff, J., Hu, C., Lang, J. E., & Chow, H. S. (2015). Plasma metabolomic profiles of breast cancer patients after short-term limonene intervention. Cancer prevention research (Philadelphia, Pa.), 8(1), 86-93.More infoLimonene is a lipophilic monoterpene found in high levels in citrus peel. Limonene demonstrates anticancer properties in preclinical models with effects on multiple cellular targets at varying potency. While of interest as a cancer chemopreventive, the biologic activity of limonene in humans is poorly understood. We conducted metabolite profiling in 39 paired (pre/postintervention) plasma samples from early-stage breast cancer patients receiving limonene treatment (2 g QD) before surgical resection of their tumor. Metabolite profiling was conducted using ultra-performance liquid chromatography coupled to a linear trap quadrupole system and gas chromatography-mass spectrometry. Metabolites were identified by comparison of ion features in samples to a standard reference library. Pathway-based interpretation was conducted using the human metabolome database and the MetaCyc database. Of the 397 named metabolites identified, 72 changed significantly with limonene intervention. Class-based changes included significant decreases in adrenal steroids (P < 0.01), and significant increases in bile acids (P ≤ 0.05) and multiple collagen breakdown products (P < 0.001). The pattern of changes also suggested alterations in glucose metabolism. There were 47 metabolites whose change with intervention was significantly correlated to a decrease in cyclin D1, a cell-cycle regulatory protein, in patient tumor tissues (P ≤ 0.05). Here, oral administration of limonene resulted in significant changes in several metabolic pathways. Furthermore, pathway-based changes were related to the change in tissue level cyclin D1 expression. Future controlled clinical trials with limonene are necessary to determine the potential role and mechanisms of limonene in the breast cancer prevention setting.
- Algotar, A., Marrero, D., Chow, H., Babiker, H. M., Dougherty, S. T., Hsu, C., Smith, T., & Thomson, C. A. (2018, Fall). Abstract: Comprehensive lifestyle improvement program for prostate cancer (CLIPP) Survivors. UACC Scientific Retreat. Tucson, AZ.
- Trujillo, J. S., Villa-Guillen, D. E., Tapia, E., Cordova, C., Chalasani, P., Thomson, C. A., Altbach, M., Gallons, J. P., Miller, J., Roe, D., Algotar, A., & Chow, H. (2018, March 2018). The potential for metformin to reduce obesity-associated breast cancer risk. American Society for Preventive Oncology, 42nd Annual Conference. New York: American Society for Preventive Oncology.
- Trujillo, J., Tapia, E. O., Villa Guillen, D. E., Chalasani, P., Martinez, J. A., Guillen-Rodriguez, J. M., Thomson, C. A., Roe, D., Galons, J., Altbach, M. I., Algotar, A., & Chow, H. (2018, Fall). Abstract: Phase II clinical study of metformin for breast cancer prevention. UACC Scientific Retreat. UACC Scientific Retreat. Tucson, AZ.