Cancer Preventive Agents Research Articles

Abstract A006: Shared gene expression and immune pathway changes associated with progression from nevi to melanoma

Abstract There is a need to identify biomarkers of melanoma progression to assist the development of chemoprevention strategies to lower melanoma incidence. In this study, we assessed the feasibility of creating a molecular signature for melanomagenesis using three publicly available RNA sequencing and microarray expression datasets. We performed differential expression and regularized regression analyses across nevi and melanoma samples to identify consistent genes associated with melanomagenesis. The regularized regression models demonstrated that a small number of genes could successfully distinguish between nevi and melanoma, providing evidence for the feasibility of creating a molecular signature. Differential expression analysis identified consistent upregulation of C1QB, CXCL9, CXCL10, DFNA5 (GSDME), FCGR1B, and PRAME in melanoma and consistent downregulation of SCGB1D2 in melanoma compared to nevi. Additionally, each of these genes demonstrated a linear association with the progression from benign nevi to dysplastic nevi, to radial growth phase melanoma to vertical growth phase melanoma, providing additional evidence for their role in melanomagenesis. Subsequent pathway analysis demonstrated significant enrichment of immune-related pathways among the differentially expressed genes. Overall, this study 1) demonstrates the feasibility of creating a gene signature for melanomagenesis and 2) highlights genes and pathways of interest for melanoma progression. We are in the process of generating a new dataset with benign nevi, dysplastic nevi, and melanoma with which to build and validate a molecular signature of melanoma. Citation Format: Elizabeth S. Borden, Anngela C. Adams, Kenneth H. Buetow, Melissa A. Wilson, Julie E. Bauman, Clara Curiel-Lewandrowski, H.-H. Sherry Chow, Bonnie J. LaFleur, Karen Taraszka Hastings. Shared gene expression and immune pathway changes associated with progression from nevi to melanoma [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A006.

Abstract A017: Lung cancer chemoprevention with the β-blocker carvedilol

Abstract Chronic exposure to carcinogens that are present in tobacco smoke is a causative factor for lung carcinogenesis. Although smoking cessation successfully reduced the prevalence of cigarette use in the US, lung cancer risk for current and former smokers remains high, for whom no effective chemopreventive agent currently exists. In the present study, carvedilol, an FDA-approved β-blocker was examined on lung carcinogenesis induced by the tobacco carcinogen benzo(a)pyrene [B(a)P] in vitro and in vivo. In non-tumorigenic human bronchial epithelial cell culture BEAS-2B, carvedilol inhibited benzo(a)pyrene diol epoxide (BPDE)-induced malignant transformation at non-toxic concentrations in a dose-dependent manner. Although β-adrenergic receptors (β-ARs) are expressed in BEAS-2B cells, the anticancer activity of carvedilol is independent of β-blockade since the non-β-blocking R-carvedilol enantiomer also blocked transformation while the β-blockers atenolol (β1-AR selective blocker), ICI-118,551 (β2-AR selective blocker), and propranolol (nonselective blocker) had no effect. Carvedilol’s anti-transformation activity is possibly mediated by aryl hydrocarbon receptor signaling because carvedilol, R- and S-carvedilol all inhibited B(a)P-activated xenobiotic responsive element (XRE) promoter and CYP1A1 mRNA expression. In a B(a)P-induced acute lung toxicity model in CD-1 mice, pretreatment with carvedilol, R- or S-carvedilol (20 mg/kg/day) for 7 days significantly attenuated increased plasma levels of lactate dehydrogenase and malondialdehyde, inflammatory cell infiltration, histopathologic changes, and overexpression of COX-2 in the lung. In a B(a)P-induced lung carcinogenesis model in A/J mice, carvedilol at 3.2 and 20 mg/kg significantly attenuated tumor multiplicity and burden, to a similar degree as the EGFR inhibitor gefitinib. Our study reveals a previously unexplored role for the FDA approved cardiovascular drug carvedilol in the prevention of tobacco carcinogen-associated lung cancer. Citation Format: Ayaz Shahid, Mengbing Chen, Carol Lin, Bradley T. Andresen, Cyrus Parsa, Robert Orlando, Ying Huang. Lung cancer chemoprevention with the β-blocker carvedilol [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A017.

Targeting apoptosis in MCF-7 and Ehrlich ascites carcinoma cells by saponifiable fractions from green and black Vitis vinifera seed oil

Grape seed (GS) oil is one of the potential functional foods. For the first time, we evaluated the therapeutic effects of GS oil saponifiable (Sap)-fraction from black (BSap) and green (GSap) grapes on MCF-7 cells and Ehrlich ascites carcinoma (EAC) in mice. The fatty acid composition of BSap and GSap was determined using gas chromatography-mass spectrometry analysis. Approximately twelve distinct fatty acids were detected in BSap and eleven in GSap. BSap showed a greater cytotoxic effect on MCF-7 cells than GSap did by inducing apoptosis and reducing inflammation, while both grape fractions had superior potency to 5-FU. Furthermore, BSap massively boosted apoptosis and lowered redox potential (Eh) and CD44+ cells in EAC cells of EAC-bearing mice more than GSap, and both fractions were more efficient than 5-FU. Blood tests and liver histopathology revealed significant improvement in EAC-induced pathological alterations with these fractions. The in silico analysis implied the competitive inhibitory impacts of the most abundant fatty acid composites in BSap and GSap on cancer-metastasis-associated proteases (cathepsin B and MMP9). Also, this analysis predicted that the apoptotic action of these Sap fractions is independent of the 5ˈAMP-activated protein kinase. Therefore, grape Sap-fraction, especially BSap, may be a useful agent for cancer prevention.

Sulforaphane inhibits CD44v6/YAP1/TEAD signaling to suppress the cancer phenotype.

Sulforaphane (SFN) is a promising cancer prevention and treatment agent that strongly suppresses the cutaneous squamous cell carcinoma (CSCC) cell cancer phenotype. We previously showed that yes-associated protein 1 (YAP1)/TEAD signaling is a key procancer stimulator of the aggressive CSCC cell cancer phenotype. However, SFN-responsive upstream regulators of YAP1/TEAD signaling are not well characterized and so there is a pressing need to identify these factors. We show that CD44v6 knockdown reduces YAP1/TEAD-dependent transcription and target gene expression, and that this is associated with reduced spheroid formation, invasion and migration. CD44v6 knockout cell lines also display reduced YAP1/TEAD activity and target gene expression and attenuated spheroid formation, invasion, migration and tumor formation. An important finding is that SFN treatment suppresses CD44v6 level leading to a reduction in YAP1/TEAD signaling and marker gene expression. Sox2 level and epithelial-mesenchymal transition (EMT) are also reduced. Forced expression of constitutive active YAP1 in CD44v6 knockdown cells partially restores the aggressive cancer phenotype. These important findings suggest that CD44v6 drives YAP1/TEAD signaling to enhance the CSCC cell cancer phenotype and that SFN treatment reduces CD44v6 level/function which, in turn, reduces YAP1/TEAD signaling leading to reduced stemness, EMT and tumor growth.

Biosynthesized silver nanoparticles and miR34a mimics mediated activation of death receptor in MCF-7 human breast cancer cell lines

Nano-biotechnology-based clinical applications to cure health-related issues have gained huge attention among the scientific community and hold great promise to limit cancer metastasis. In this study, green-derived silver nanoparticles were synthesized by using leaf extract of Litchi chinensis. Characterization of biosynthesized silver nanoparticles was performed by using UV–Vis spectroscopy, FTIR, XRD, EDS, and SEM analysis. The clinical application of green-drive nanoparticles was investigated by using MCF-7 cancer cell lines. MCF-7 breast cancer cell lines were analyzed against three different treatments. (i) Silver nanoparticles (AgNPs), (ii) miR34a mimics and (iii) Co-delivery of AgNPs and miR34a mimics. Cell viability was determined by MTT assay and, extraction of mRNA and cDNA synthesis were performed after successful cellular transfection. qRT-PCR was done for expression analysis of DR4 and DR5 upon exogenous delivery of all 3 treatments. Results indicate that L. chinensis leaves have a significant amount of phenolic and flavonoid contents and also possess massive antioxidant activity. The diameter of nanoparticles was observed in the range of 41–55 nm. It was concluded that green-derived silver nanoparticles can be a potential contributing agent for cancer prevention and are reported to upregulate the expression of DR4 and DR5 by 0.8-folds and 3.7-folds, respectively.

A Review on Ethnopharmacological Applications, Pharmacological Activities, and Bioactive Compounds of Mimosa pudica (Linn.)

In the current investigation, made endeavours to audit on a pharmacological movement of Mimosa pudica (Linn.) having a grade with family mimisace. Mimosa pudica (Linn.) is a swarming yearly or enduring herb. It has been documented as lajjalu in Ayurveda. It is called the delicate Plant, humble Plant, disgrace plant, resting grass, contactmenot, namaskari in Sanskrit, chuimui, lajwanti, snoozing grass, unstable Plant, humble Plant, hesitant Plant, get in touch with me not, and various names. The whole Plant of Mimosa pudica (Linn.) is beneficial for different pharmacological and natural exercises. For the most part, roots and leaves of Mimosa pudica (Linn.) are demonstrated the most excellent pharmacological action as hostile to the diabetic, counteragent, antihepatotoxic, cancer prevention agent, and wound recuperating movement, diuretic, anticancer, anticonvulsant. The herb has been used traditionally for ages to treat urogenital disorders, piles, dysentery, sinus, and applied on wounds. This work explores and compiles the different pharmacognostic and pharmacological aspects of the action plant M. pudica reported to date.

The Formulation and Stability Test of The Balm Emprit Ginger (Zingiber officinale var. amarum) Essential Oil

Emprit ginger (Zingiber officinale var. amarum) is a rhizome plant that is much of the time tracked down in the locale. Tanasitolo, Kab. Wajo. Its utilization is most generally utilized as a cooking zest, defeating joint inflammation, muscle torment, treating colds, treating hacks, as a characteristic cell reinforcement and warming the body. The compound parts contained in emprit ginger (Zingiber officinale var. amarum) are zingiberene, shagaol, sap, and gingerol which are adequate as cancer prevention agents and mitigating or then again reflexology. This study aims to decided how to of ginger emprit (Zingiber officinale var. amarum) as a salve form of a natural balm. This type of research is a direct observation in the laboratory using the distillation method to obtain the essential oil in ginger emprit (Zingiber officinale var. amarum) was then made in the form of a balm with different concentrations of essential oils, namely F1 (0 g), F2 (1.5 g), and F3 (2 g) using accelerated stability testing on the balm preparation, stored for 6 days with 3 cycles (40C and 400C) the observations included organoleptic tests (shape, smell, and colour), homogeneity test, pH test, spreadability test, adhesion test, and specific gravity.. This study indicate that a stable balm preparation that meets the standard requirements based on SNI with accelerated stability testing is formula F3 with a concentration of 2 grams of ginger essential oil. Emprit ginger (Zingiber officinale var. amarum) can be formed in a balm preparation.

In Vitro anti-metastasis of Perilla frutescens leaf water extract on aggressive human breast cancer cells

Background: Perilla frutescens is a long-established plant that is often used in foods and traditional medicines in Asian countries. The perilla leaf contains a considerable number of bioactive substances, such as phenolics and flavonoids, which have been demonstrated to possess anticancer activity in vitro and in vivo. Objectives: We aimed to study anti-metastatic activity, anti-invasion activity, and anti-migration activity of perilla leaf water extract (PLW) at 90°C for 1-5 min in MDA-MB-231 aggressive human breast cancer cells. Materials and methods:Dry perilla leaves were extracted using hot water for 1-5 min to obtain crude extract and then lyophilized for PLW powder. PLW was evaluated for total phenolic, total flavonoid, and rosmarinic acid (RA) contents by Folin-Ciocalteau reagent, aluminum chloride colorimetric assay, and ultra-high-pressure liquid chromatography, respectively. Antioxidant activity of PLW was determined by DPPH and ABTS assays. MTT assay was performed to evaluate the cytotoxicity of PLW on MDA-MB-231 cells. Effective PLW was further determined its inhibitory effect on human breast cancer cell metastasis by a Boyden chamber-based transmembrane assay, the MMP-9 activity, and the proteolytic type IV collagenase activity. Results: PLW by 5-min infusion showed the highest amount of total phenolic and flavonoid contents, as well as RA. Moreover, by the 5-min infusion, PLW had the highest antioxidant capacity when compared to PLW by infusions for 1-4 min. Following that, cytotoxicity testing revealed that the PLW is not toxic to MDA-MB-231 cells after a 24-hr exposure. The PLW at non-toxic doses (12.5-100 µg/mL) intensely presents an inhibitory effect on cell invasion and migration. The gelatinolytic activity showed that the PLW at concentrations of 12.5-100 µg/mL decreases MMP-9 activity in a dose-related manner. Furthermore, after treatment with the PLW, the proteolytic type IV collagenase activity was reduced considerably in a dose-related manner. Conclusion: Our findings further showed that the PLW samples inhibit proteolytic enzymes involved in basement membrane breakdown, which might explain the anti-invasion and anti-migration properties of breast cancer cells. From the result, the application of perilla leaf might be developed as an herbal tea and used as an anti-metastatic agent for breast cancer prevention and treatment.

Comprehending the Presence and Application of Antiradicals and Antioxidants within the Human Body

A substance that prevents other molecules from oxidising is known as an antioxidant1. A chemical process called oxidation can generate free radicals, which can set off a series of events that can harm cells. Ascorbic acid, an antioxidant, stops these cascades of events. Reactive-oxygen species (ROS) are produced in excess by plants and animals as a result of various abiotic stressors. ROS are extremely sensitive and toxic, damaging proteins, lipids, carbohydrates, and DNA as a result, which causes oxidative stress. This oxidative-stress damages tissues and contributes to a broad range of illnesses2. Antioxidants counteract the effects of ROS and aid in disease prevention by balancing their effects. Antioxidants can be naturally occurring or synthetic. Common cancer preventatives are ingested through diet because they are present in organic foods, veggies, and flavours. Additionally, several designed cancer preventative substances like BHT and BHA prevent oxidation. The search for non-toxic cancer prevention agents has gotten stronger in recent years, nonetheless, as it has been determined that these synthetic cancer prevention agents pose risks to people.
 Keywords: Parkinson's disease, Parkinson's cancer, ascorbic acid, and tocopherols.

Synergism effect of iron nanoparticles with Ocimum Basilicum L. on breast cancer cell

Breast cancer is the second leading cause of cancer deaths among women. The development of breast cancer is a multi-step process involving multiple cell types, and its prevention remains challenging in the world. Early diagnosis of breast cancer is one of the best approaches to prevent this disease. In some developed countries, the 5-year relative survival rate of breast cancer patients is above 80% due to early prevention. For people presenting without metastatic disease, therapeutic goals are tumor eradication and preventing recurrence. Ocimum basilicum L. (Basil) is a plant that has a place with the family Labiatae, also basil leave have activities intense cancer prevention agents, curbs aging, is an anticancer, antiviral, and has antimicrobial properties. This study aimed to determine effect of nanotechnology with basil as synergism effect on breast cancer cell also showing the side effect of treatment on normal cells. In this work breast cancer cells (MDA and MCF7) was treated with Iron nanoparticle that prepared by Cold Atmospheric Plasma (CAP) and Ocimum Basilcum L. (Basil) as synergism effect on the cells.

Biotransformation of (-)-Isopulegol by Rhodococcus rhodochrous.

The ability of actinobacteria of the genus Rhodococcus to biotransform the monoterpenoid (–)-isopulegol has been established for the first time. R. rhodochrous strain IEGM 1362 was selected as a bacterium capable of metabolizing (–)-isopulegol to form new, previously unknown, 10-hydroxy (2) and 10-carboxy (3) derivatives, which may presumably have antitumor activity and act as respiratory stimulants and cancer prevention agents. In the experiments, optimal conditions were selected to provide the maximum target catalytic activity of rhodococci. Using up-to-date (TEM, AFM-CLSM, and EDX) and traditional (cell size, roughness, and zeta potential measurements) biophysical and microbiological methods, it was shown that (–)-isopulegol and halloysite nanotubes did not negatively affect the bacterial cells. The data obtained expand our knowledge of the biocatalytic potential of rhodococci and their possible involvement in the synthesis of pharmacologically active compounds from plant derivatives.

Phytocompounds from the Medicinal and Dietary Plants: Multi-target Agents for Cervical Cancer Prevention and Therapy.

Cervical cancer is the fourth leading cause of cancer death among women worldwide. Due to cervical cancer's high incidence and mortality, there is an unmet demand for effective diagnostic, therapeutic, and preventive agents. At present, the preferred treatment strategies for advanced metastatic cervical cancer include surgery, radiotherapy, and chemotherapy. However, cervical cancer is gradually developing resistance to chemotherapy, thereby reducing its efficacy. Over the last several decades, phytochemicals, a general term for compounds produced from plants, have gained attention for their role in preventing cervical cancer. This role in cervical cancer prevention has garnered attention on the medicinal properties of fruits and vegetables. Phytochemicals are currently being evaluated for their ability to block proteins involved in carcinogenesis and chemoresistance against cervical cancer. Chemoresistance to cancer drugs like cisplatin, doxorubicin, and 5-fluorouracil has become a significant limitation of drug-based chemotherapy. However, the combination of cisplatin with other phytochemicals has been identified as a promising alternative to subjugate cisplatin resistance. Phytochemicals are promising chemo-preventive and chemotherapeutic agents as they possess antioxidant, anti-inflammatory, and anti-proliferative potential against many cancers, including cervical cancer. Furthermore, the ability of the phytochemicals to modulate cellular signaling pathways through up and down regulation of various proteins has been claimed for their therapeutic potential. Phytochemicals also display a wide range of biological functions, including cell cycle arrest, apoptosis induction, inhibition of invasion, and migration in cervical cancer cells. Numerous studies have revealed the critical role of different signaling proteins and their signaling pathways in the pathogenesis of cervical cancer. Here, we review the ability of several dietary phytochemicals to alter carcinogenesis by modulating various molecular targets.

Ezetimibe and Cancer: Is There a Connection?

The high level of serum cholesterol caused by the excessive absorption of cholesterol can lead to hypercholesteremia, thus promoting the occurrence and development of cancer. Ezetimibe is a drug that reduces cholesterol absorption and has been widely used for the treatment of patients with high circulating cholesterol levels for many years. Mechanistically, ezetimibe works by binding to NPC1L1, which is a key mediator of cholesterol absorption. Accumulating data from preclinical models have shown that ezetimibe alone could inhibit the development and progression of cancer through a variety of mechanisms, including anti-angiogenesis, stem cell suppression, anti-inflammation, immune enhancement and anti-proliferation. In the past decade, there has been heated discussion on whether ezetimibe combined with statins will increase the risk of cancer. At present, more and more evidence shows that ezetimibe does not increase the risk of cancers, which supports the role of ezetimibe in anti-cancer. In this review, we discussed the latest progress in the anti-cancer properties of ezetimibe and elucidated its underlying molecular mechanisms. Finally, we highlighted the potential of ezetimibe as a therapeutic agent in future cancer treatment and prevention.

Extensive Study of DFT-Quantum Calculations Based QSAR Modeling of Fused 1,2,4-Triazine Derivatives Revealed Potent CYP1A1 Inhibitors

In a continuing effort for our research group, we identify new active 1,2,4-triazine derivatives as novel cancer preventive agents that target CYP1A1 activity, through the application of quantitative structure–activity relationship (QSAR) theory. For this purpose, novel fused 1,2,4-triazine derivatives, namely, 4-Amino-6-substituted benzyl-3-(2-substituted benzylidenehydrazinyl)-1,2,4-triazin-5(4H)-ones and acetylated 6-substituted benzyl-7-oxo-3-substituted phenyl-2,3-dihydro-7[Formula: see text]-[1,2,4]triazolo[4,3-[Formula: see text]][1,2,4]triazine analogs were utilized for the prediction of the QSAR model. Furthermore, the application of this QSAR equation served successfully as a rational guide for predicting the activities of newly synthesized analogs. The DFT calculation was applied to recognize the physicochemical parameters at B3LYP/6- 311G* level to gain a clear view of global and local molecular reactivity. Besides, the molecular features of the investigated compounds were identified through HOMO, LUMO and molecular electrostatic potential (MEP) which were plotted to determine the charge transfer within the molecules. Promising two novel 1,2,4-triazine compounds were identified with observed significant inhibitions (83% and 67%) and CYP1A1 activity was predicted. The chemical configuration of the two actives showed good alignment of [Formula: see text]-methoxy benzyl aminotriazinone fragments, hydrazino and carbonyl linker in structure–activity relationship and interaction. Molecular modeling analysis supported with MD simulations was undertaken to investigate different binding interactions with the target binding site. These projects offered a good application of a promising QSAR model for prediction of highly active compounds for further lead optimization.

Proton Pump Inhibitor Use and Obesity-Associated Cancers in the Women's Health Initiative

Purpose: Proton pump inhibitors (PPIs) inhibit fatty acid synthase (FAS), a critical enzyme in lipogenesis, energy balance, and cancer cell survival. We aimed to evaluate the association of PPI use with incidence of common obesity- related cancers in women: postmenopausal breast, colorectal, and endometrial cancers. Methods: Our study included 124,931 postmenopausal who were enrolled in the Women's Health Initiative (WHI) observational study and clinical trials, and had responded to a year 3 follow-up assessment. We examined prescription and over the counter use of PPI and/or histamine 2 receptor antagonists (H2RA) at baseline and year 3, to isolate potential effects of FAS inhibition by PPI rather than simply acid suppression. Incident cancer cases were physician-adjudicated. Cox proportional hazard regression models were used to estimate multivariable hazard ratios (HR) and 95% confidence intervals (CI) for associations between PPI and/or H2RA use and cancer incidence after year 3. Results: There were 7956 PPI ever users (with or without H2RA use) and 9398 H2RA only users. PPI or H2RA use was not associated with risk of breast cancer (n=9186 cases), compared to women who did not use either agent (HR 1.01, 95% CI 0.93-1.10 and HR 0.95 95% CI 0.87-1.03, respectively). The incidence of colorectal cancer (n=2280) was significantly lower in PPI users (HR 0.75, 95% CI 0.61-0.92), but not in H2RA users (HR 1.13, 95% CI 0.97-1.31). This association was strengthened with increasing duration (p=0.006) and potency (p=0.005) of PPI use and held regardless of BMI or NSAID use. PPI or H2RA use was not associated with endometrial cancer (n=1231) (HR 0.81, 95% CI 0.61-1.07 and HR 1.13, 95% CI 0.91-1.40, respectively), but showed a trend in decreased risk with increasing PPI potency (P=0.048). Conclusions: Among postmenopausal women, PPI use, but not H2RA use, demonstrated an inverse, dose-responsive association with colorectal cancer incidence. This was consistent with preclinical data that FAS inhibition prevents colon cancer progression and supports further investigation of this commonly used medication as a cancer preventive agent. PPI use was not associated with incidence of breast or endometrial cancer.

Clinical evaluation of coffee based gel on gingivitis: A randomised controlled clinical trial

Introduction: Gingivitis is a non -destructive, plaque induced infection that causes inflammation of the gingiva. Coffee is considered to be the biggest source of dietary cancer prevention agents in industrialized countries. Caffeine, caffeic corrosive and chlorogenic corrosive are the dynamic components of coffee that have found to have anti-inflammatory and anti-oxidative impacts.Objective: To evaluate the effectiveness of Coffee as an oral gel in the reduction of plaque and gingivitis.Materials and Method: This single center, randomized controlled clinical trial was carried out among 30 participants with mild to moderate gingivitis. Group I, Scaling with application of coffee gel (Test) and Group II, Scaling only (Control) [n=15]. Group I subjects were instructed to use coffee gel twice daily following scaling. Clinical parameters (Turesky Gilmore Glickman Modification of Quigley Hein Plaque Index and Loe and Silness Gingival Index) were recorded at baseline,15 day and 1month post-operatively. Student’s paired t test and Independent t-test were used for intra and inter group comparison of clinical parameters.Result: On intragroup comparison, both the groups showed a statistically significant difference at 1 month. But on intergroup comparison, there was no statistically significant difference between the test group and control group.

Abstract 717: Title: Modulation of local cholesterol biosynthesis and response to oxidative stress in high-risk postmenopausal breast tissue with licochalcone A from licorice

Abstract Background: The risk of breast cancer increases with age, despite a drastic decline in circulatory estrogen after menopause. Women at increased risk can reduce this by use of anti-endocrine agents, but often decline these drugs to their adverse effects. Therefore, alternative strategies with greater acceptability are needed. We have previously shown that licochalcone A (LicA) from licorice (Glycyrrhiza inflata) suppresses aromatase expression and activity, enhances the activity of detoxifying phase II metabolism enzymes, and reduces estrogen genotoxic metabolism in cell lines and animal models. However, its effects on the breast tissue of high-risk women have not been studied. We hypothesize that LicA creates a tumor preventive environment in the breast by locally modulating cholesterol and steroid hormone biosynthesis, and antioxidant/anti-inflammatory response. Methods: We prepared microstructures from fresh tissue of contralateral unaffected mastectomy specimens of 6 postmenopausal women with incident unilateral breast cancer. We exposed these microstructures to DMSO (control) and LicA (5 µM) for 24 h. After total RNA sequencing, we examined differential gene expression between treated and control samples using the limma R package. Enrichment results were generated by analyzing the up-regulated and down-regulated gene sets using Enrichr. A gene ontology (GO) pathway analysis was performed. The enriched pathways with combined enrichment scores > 4 and FDR < 0.05 were considered statistically significant. We performed confirmatory qPCR experiments in samples obtained from 18 additional women. Results: We observed significant (P < 0.05) upregulation up to 8-fold of antioxidant genes NQO1, HMOX1, G6PD, SQSTM1, PGD, and GPX2. Significant upregulation of Nrf2, the transcription factor involved in the activation of antioxidant enzymes, was evident. In addition, we observed the significant (P < 0.05) downregulation, ranging from 4 to 32-fold of cholesterol biosynthesis and transport genes, MSMO1, FDPS, EBP, SQLE, MVD, MVK, IDI1, DHCR7, NSDHL, FDFT1, LSS, ABCA1, ABCC3, ABCG1, steroid hormone biosynthesis genes HSD17B7, STS, CYP1A1, and CYP1B1, as well as lipid metabolism genes ACAT2, ACYL, FADS1, FADS2, ELOV6, CYP51A1, and LDLR. Some of the genes are shared between these pathways. The significant upregulation of the regulators of these pathways, SREBF1 and SREBF2 provided further confirmation. Conclusion: Our data suggest that LicA can lead to a tumor-preventive breast microenvironment by reducing cholesterol and steroid hormones and lowering oxidative stress mediators. These observations along with the popularity of natural products, suggests that LicA might be a good candidate to be studied further as an alternative breast cancer prevention agent. Citation Format: Atieh Hajirahimkhan, Elizabeth Bartom, Susan Clare, Seema A. Khan. Title: Modulation of local cholesterol biosynthesis and response to oxidative stress in high-risk postmenopausal breast tissue with licochalcone A from licorice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 717.

Phase II trial of weekly erlotinib dosing to reduce duodenal polyp burden associated with familial adenomatous polyposis

ImportancePatients with familial adenomatous polyposis (FAP) are at markedly increased risk for duodenal adenomas and cancer. Combination sulindac and erlotinib was previously shown to reduce duodenal polyp burden but was...

Resveratrol Decreases the Invasion Potential of Gastric Cancer Cells

The cancer-preventive agent Resveratrol (RSV) [3,5,4′-trihydroxytrans-stilbene] is a widely recognized antioxidant molecule with antitumoral potential against several types of cancers, including prostate, hepatic, breast, skin, colorectal, and pancreatic. Herein, we studied the effect of RSV on the cell viability and invasion potential of gastric cancer cells. AGS and MKN45 cells were treated with different doses of RSV (0–200 μM) for 24 h. Cell viability was determined using the Sulphorhodamine B dye (SRB) assay. For invasion assays, gastric cells were pre-treated with RSV (5–25 μM) for 24 h and then seeded in a Transwell chamber with coating Matrigel. The results obtained showed that RSV inhibited invasion potential in both cell lines. Moreover, to elucidate the mechanism implicated in this process, we analyzed the effects of RSV on SOD, heparanase, and NF-κB transcriptional activity. The results indicated that RSV increased SOD activity in a dose-dependent manner. Conversely, RSV significantly reduced the DNA-binding activity of NF-κB and the enzymatic activity of heparanase in similar conditions, which was determined using ELISA-like assays. In summary, these results show that RSV increases SOD activity but decreases NF-kB transcriptional activity and heparanase enzymatic activity, which correlates with the attenuation of invasion potential in gastric cancer cells. To our knowledge, no previous study has described the effect of RSV on heparanase activity. This article proposes that heparanase could be a key effector in the invasive events occurring during gastric cancer metastasis.

In vitro anticancer activity of medicinal plants of Himalayan region

Plant-derived products have gained attention over the past few years due to their potential as novel cancer preventive and therapeutic agents. Himalayan region is known for its vast reserve of natural resources. The present study was planned with the objective to explore the anticancer potential of plants of Himalayan region. Total twenty lyophilized plant extracts were prepared after extraction with 70 % ethanol. All plant extracts were evaluated for percent cytotoxicity against LC-540 Leydig Cell Testicular Tumor cell line (rats) at various concentration levels (20, 50, 100 and 200 µM) and at different time of incubation (24, 48, 72 h). The results revealed that the aqua-ethanolic extract of leaves of Camellia sinensis exhibited maximum anticancer activity among all twenty extracts screened, with 42.74 ± 4.63 % and 68 ± 1.74 % cytotoxicity at 100 µM and 200 µM concentration respectively, followed by Lantana camara, Tinospora cordiofolia and Cedrus deodara. Further exploration of in vivo antineoplastic effects and probable mechanism of action of its potent phyto-constituents could be highly useful in developing an effective herbal formulation in cancer therapeutics.