Drugs For Cancer Prevention Research Articles

Phytochemistry of Petroselinum crispum (Mill.) Fuss, Murraya koenigii (L.) Spreng. and Cinnamomum tamala (Buch.-Ham.) T. Nees & C. H. Eberm. and in silico studies of the role of their bioactive components against cancer

Phytochemical profiling using reliable equipment and validated methods helps us know the medicinal value of the plants. Since natural compounds have fewer side effects, they can serve as replacements for synthetic drugs that are being used in the treatment of challenging chronic diseases like cancer. The present study focuses on the bioactive phytochemical profiling of Petroselinum crispum (Mill.) Fuss, Murraya koenigii (L.) Spreng., and Cinnamomum tamala (Buch.-Ham.) T. Nees & C. H. Eberm. and in silico studies to check the anticancer potential of their bioactive components. In thin-layer chromatography (TLC) plate analysis, it was found that the methanolic extracts of plants contained the maximum number of components. Gas chromatography–mass spectrometry (GC-MS) analysis of the methanolic extracts of plants showed the presence of 22 bioactive components. High-performance thin-layer chromatography (HPTLC) analysis of the extracts of these plants showed the important chromatographic peak, apigenin. In silico studies showed the binding efficacy of selected bioactive components observed in the analysis of plant extracts. Amongst them, apigenin was found to be most effective at binding to the receptors of targeted cancer cells, viz., hepatocellular carcinoma, lung, and breast cancer. After the analysis of the study, it was arrived at the conclusion that the plants, viz., P. crispum, M. koenigii, and C. tamala, possess various bioactive components, and some of these components have anticancer potential. Therefore, in vivo and in vitro studies should be essentially conducted for the development of cancer-preventive drugs.

Natural Alkaloids and Mechanisms for Anti-cancer Action: A Review

: Cancer is a global public health issue. Cancer therapy has been hampered by the issue of multidrug resistance, which is one of the leading causes of death worldwide. As a result, the use of natural derived drugs for cancer prevention and therapy has been researched and developed for decades. Alkaloids are plant-derived secondary metabolites that have antiproliferative and anticancer effects on several forms of cancer. Camptothecin and vinblastine, two anticancer medicines derived from alkaloids, have been adequately developed in the past. Alkaloids, a drug lead compounds, derived from natural products, have the advantage of being used by the host, making them suitable for further exploitation. The current review looks at the anticancer potential of numerous naturally occurring alkaloids, as well as the mechanism behind their anticancer effect.

Repurposing Drugs for Cancer Prevention: Targeting Mechanisms Common to Chronic Diseases.

The development of agents for cancer prevention is a lengthy process requiring a delicate balance between the safety and tolerability of potential interventions and effectiveness in preventing future cancer. Individuals at risk for a specific cancer are frequently at risk for multiple types of cancer as well as other chronic diseases, especially ones associated with aging. Shared environmental exposures, genetic predisposition, metabolic factors, and commonalities in pathogenesis suggest opportunities for combined targeting of cancer and other chronic diseases. Examples discussed here include mechanisms shared between various cancers and obesity, diabetes, and cardiovascular disease.

BRCAFem: A database for breast cancer research.

Amid extensive breast cancer research, valuable data and findings often remain scattered across published literature, databases and web resources, posing challenges for researchers and practitioners in curating specific datasets, genes and relevant information. Hence, we developed BRCAFem (BReast CAncer of Females), an integrated database for breast cancer research. BRCAFem includes 1220 breast cancer genes, 82 FDA-approved breast cancer prevention and treatment drugs and 33 sequencing and imaging datasets. Additionally, BRCAFem provides general information about breast cancer, global statistics, risk factors, treatment options and blogs related to recent updates in breast cancer research.

Antibiotics: the triumph of civilization and its other side

The synthesis of antibacterial drugs and their subsequent use in clinical practice contributed to saving a huge number of people’s lives in the global space. At the same time, they can cause significant harm, including Clostridium difficile infections, in the formation of antibiotic resistance and changes in the human microbiome, the consequences of which have yet to be assessed. Antibiotic management programs are becoming more and more commonplace in modern clinical practice, requiring extensive knowledge based on clinical, genomic and laboratory data. Increasing evidence suggests a role for antibiotics in the manifestation of allergic, inflammatory, metabolic, and functional diseases. On the other hand, there is more and more data on the role of antimicrobial drugs in cancer prevention and treatment of viral diseases.

The protective role of phosphodiesterase inhibitors in preventing colorectal cancer and advanced colorectal polyps: a systematic review and meta-analysis.

Inflammatory cells within the tumour microenvironment are the driving forces behind colorectal cancer (CRC) tumourigenesis. Understanding the different pathways involved in CRC carcinogenesis paves the way for effective repurposing of drugs for cancer prevention. Emerging data from preclinical and clinical studies suggest that, due to their antiproliferative and anti-inflammatory properties, phosphodiesterase-5 inhibitors (PDE5i) might have an anticancer effect. The aim of this study was to clarify through systematic review and meta-analysis of published peer-reviewed studies whether an association exists between PDE5i use and CRC risk. This study was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective registration was performed on PROSPERO (CRD42022372925). A systematic review was performed for studies reporting CRC and advanced colorectal polyp incidence in PDE5i 'ever-users' and PDE5i 'never-users'. Meta-analysis was performed using RevMan version 5. Four observational cohort studies and two case-control studies, comprising 995 242 patients were included in the final analysis, of whom 347 126 were PDE5i ever-users. Patients who were PDE5i ever-users had a significantly lower incidence of CRC or advanced colorectal polyps than never-users (OR 0.88, CI 0.79-0.98, p = 0.02). To examine the primary preventative role of PDE5i, subgroup analysis of four studies including patients without a previous history of CRC found that use of PDE5i was associated with a lower incidence of CRC (OR 0.85, CI 0.75-0.95, p = 0.005, I2 = 64%). There was no significant temporal relationship found between PDE5i use and CRC risk as both current users and previous users had a significantly lower incidence of CRC than never-users. Our study found a significant anticancer effect of PDE5i, as shown by a reduced risk of CRC in the context of both primary and secondary CRC prevention.

Identification of Potential Drugs for Colorectal Cancer Chemoprevention through Computational Analysis

Introduction: Colorectal cancer is one of the common causes of hospitalizations, readmission, and poor quality of life due to disability, pain, and death. Most drugs identified to provide chemoprevention in colorectal cancer, such as NSAIDs, have a high level of toxicity. There is need to find novel drugs targeting colorectal cancer with favorable clinical profiles. Objective: The study aimed to identify possible colorectal cancer prevention drugs by comparing the docking scores (representing potential biologic activity) of Aspirin, Sulindac, and Celecoxib with their structurally similar analogs. Materials and Methods: Ligand-based virtual screening and structure-based virtual screening were done for aspirin, sulindac and celecoxib to identify potential drug-like compounds. Compounds that passed the screening, pharmacokinetic profiling, and toxicity testing were considered possible drugs for colorectal cancer chemoprevention. Results: The study identified 7 drug-like compounds from the ZINC database. ZINC02570895, with a better docking score than celecoxib coupled with favorable toxicity and metabolic profiles, was the most appropriate drug candidate for the inhibition of PDK-1. ZINC22309227, with a better docking score and favorable pharmacokinetic profile than sulindac was the most appropriate compound for further development into a MAP Kinase inhibitor. ZINC39406706, ZINC26469982, ZINC01847506, ZINC3382343, and ZINC01682308 had favorable toxicity profiles compared to aspirin and were most suitable for development of cyclooxygenase inhibitors in colorectal cancer prevention. Conclusion: In-vivo and in-vitro tests are needed to ascertain the biological activity, synthesizability and clinical use of the compounds.

Abstract P004: Targeting the RXR pathway for the prevention of triple-negative breast cancer

Abstract Background: Triple-negative breast cancer (TNBC) is an aggressive cancer that lacks expression of the estrogen receptor (ER), progesterone receptor, and Erb-B2 receptor tyrosine kinase 2. TNBC patients exhibit a poor prognosis, even if treated with chemotherapy. Although studies using selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AIs) have shown that breast cancer prevention is feasible, these drugs do not prevent ER-negative or TNBC tumors. It has been shown by our laboratory and others that retinoid X receptor (RXR)-specific ligands (rexinoids) can prevent breast cancers that are both ER-positive and ER-negative in mice. In our previous studies in MMTV-erbB2 mice, IRX-4204, a fourth generation rexinoid, prevented the development of most HER2/erbB2-positive tumors in these mice. For this study, we hypothesized that by targeting RXR pathway, we can prevent the development of triple negative, BRCA1-mutant mammary tumors in mice. To test the hypothesis, we treated MMTV-Cre/BRCA1co/co/p53+/- mice prior to their developing tumors with IRX-4204 to determine whether this RXR agonist effectively prevents triple-negative breast tumors. Methods: We tested the tumor preventative effect of IRX-4204 using the established MMTV-Cre/BRCA1co/co/p53+/- mouse model. These mice were produced by breeding MMTV-Cre/BRCA1co/co/p53+/- males and MMTV-Cre/BRCA1co/co/p53+/+ females, and female pups were PCR genotyped. All mice were separated into 4 groups: 1) sesame oil control, 2) IRX-4204 (10 mg/kg), 3) IRX-4204 (20 mg/kg) and 4) 9-cis-UAB-30 (5 mg/kg). All treatments were given by oral gavage, five days a week from 4 months of age. Mice were observed daily for tumor formation and toxicity. The percentage of tumor free mice were recorded, from which tumor incidence and time to tumor formation was visualized using Kaplan Meier curves and analyzed using the Log-rank test. Results: In MMTV-Cre/BRCA1co/co/p53+/- mice, IRX-4204 reduced tumor incidence and was associated with an increase in median tumor free survival time from 209 days to 336 days at 10 mg/kg dose (p=0.005). At the higher dose (20 mg/kg) IRX-4204 also delayed tumor formation with median tumor free survival from 209 days to 260 days (p=0.039). The rexinoid 9-cis-UAB 30 also significantly delayed tumor formation in MMTV-Cre/BRCA1co/co/p53+/- mice with median survival from 209 days to 270 days (p=0.04). Long term treatment of IRX-4204 was not associated with any toxicity. Conclusion: RXR agonist IRX-4204 delayed ER-negative mammary tumor formation in BRCA1co/co; MMTV-Cre; p53+/- mice. Based on our results, IRX-4204 is an effective cancer preventive drug without observed toxicity. Our results suggest that studies with reduced IRX-4204 dose alone or in combination with other targeted therapies such as selective estrogen receptor modulators are warranted. In the future, clinical trials of the IRX-4204 should be considered for the prevention of breast cancer in high-risk patients. (Supported by NCI-PREVENT contract to P. Brown and A. Mazumdar HHSN26100008). Citation Format: Cassandra Moyer, Jamal Hill, Darian Coleman, Shizuko Sei, Altaf Mohammed, Martin Sanders, Powel Brown, Abhijit Mazumdar. Targeting the RXR pathway for the prevention of triple-negative breast cancer. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P004.

Antiplatelet drugs and breast cancer risk in a large nationwide Danish case-control study.

Low-dose aspirin has been hypothesized to prevent cancer risk by inhibiting platelet aggregation. However, the anti-cancer effect of low-dose aspirin has recently been questioned and its effect on breast cancer development remains unclear. The impact of other antiplatelet drugs on breast cancer risk has rarely been evaluated. Thus, this study aimed to investigate the associations between breast cancer risk and antiplatelet drug use in a nationwide nested case-control study. From the Danish healthcare registries, we identified as cases all women with invasive breast cancer diagnosis between 2001 and 2018 (n=68 852). The date of diagnosis corresponded to the index date. We matched cases to 10 population controls on age and calendar time, using risk set sampling. Controls were assigned the same index date as their matched case. We used the prescription registry to identify exposure to low-dose aspirin, clopidogrel and dipyridamole. We defined ever use of antiplatelet drugs as at least two prescriptions filled up to 1 year before the index date. We applied conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals for breast cancer associated with the use of antiplatelet drugs, overall, by breast cancer subtype and by cumulative dose. Twelve percent of women had ever been exposed to low-dose aspirin, 2% to clopidogrel and 2% to dipyridamole. In multivariable models, breast cancer risk was not associated with ever use of low-dose aspirin (OR=1.00 [0.97-1.03]), clopidogrel (OR=0.93 [0.87-1.00]), and dipyridamole (OR=1.02 [0.94-1.10]), compared with never use, and there was no evidence of a dose-response relation. However, we found an inverse association between dipyridamole use and breast cancer risk among women aged <55 years old, with suggestion of a dose-response relationship (OR per 1000 Defined Daily Doses=0.72 [0.54-0.95]). Associations did not differ by breast cancer histological type, estrogen receptor status or clinical stage at diagnosis. Overall, the findings from this study do not support the use of antiplatelet drugs for breast cancer prevention.

Salicylic acid directly binds to ribosomal protein S3 and suppresses CDK4 expression in colorectal cancer cells

Colorectal cancer is a significant cause of morbidity and represents a serious public health issue in many countries. The development of a breakthrough preventive method for colorectal cancer is urgently needed. Aspirin has recently been attracting attention as a cancer preventive drug, and its inhibitory effects on the development of various cancers have been reported in several large prospective studies. However, the underlying molecular mechanisms have not yet been elucidated in detail. In the present study, we attempted to identify the target proteins of aspirin using a chemical biology technique with salicylic acid, the main metabolite of aspirin. We generated salicylic acid-presenting FG beads and purified salicylic acid-binding proteins from human colorectal cancer HT-29 cells. The results obtained showed the potential of ribosomal protein S3 (RPS3) as one of the target proteins of salicylic acid. The depletion of RPS3 by siRNA reduced CDK4 expression and induced G1 phase arrest in human colorectal cancer cells. These results were consistent with the effects induced by the treatment with sodium salicylate, suggesting that salicylic acid negatively regulates the function of RPS3. Collectively, the present results show the potential of RPS3 as a novel target for salicylic acid in the protective effects of aspirin against colorectal cancer, thereby supporting RPS3 as a target molecule for cancer prevention.

Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review.

The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.

Abstract 715: Targeting the mTOR pathway for the prevention of er-negative breast cancer

Abstract Background: Triple-Negative breast cancer (TNBC) is an aggressive cancer that lacks expression of the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. These cancers have a poor prognosis and are treated predominantly with chemotherapy. Therefore, we are working to find preventive therapies for these potentially lethal cancers. Dysregulation of PI3K-mTOR pathway is commonly associated with TNBC and other ER-negative breast cancers. We hypothesized that targeting mTOR may prevent development of ER-negative breast cancers and in this study tested whether the mTOR inhibitor, everolimus, prevents cancer in several mouse models of ER-negative breast cancer. Methods: MMTV-erbB2 mice were purchased from the Jackson Laboratory. C3(1)/SV40TAg and BRCA1co/co;MMTV-Cre;p53+/- were generated through breeding. P53-null and p53-mutant mammary gland mice were generated by transplanting p53-null or p53-mutant mammary glands into cleared fat pads of p53-wild type mice. The mice were treated with either control or everolimus (5mg/kg), administered by oral gavage daily (5X/week). All mice develop palpable mammary tumors within 8-12 months. Mice were observed daily for tumor formation and drug toxicity. The percentage of tumor free mice was recorded, and time to tumor development was visualized using Kaplan-Meier curves and analyzed using the generalized Wilcoxon test. Results: Treatment with everolimus significantly increased median survival of all mouse models. Everolimus treatment was also able to completely prevent mammary tumor formation in 27% of C3(1)/SV40Tag mice and 44% p53-mutant mammary gland mice. In p53-null mammary gland mice, 46% of control mice had developed tumors after 420 days, compared to 7% of everolimus treated mice. Long term treatment of everolimus was associated with mild toxicity that includes slight weight loss (&amp;lt;10%) and skin changes (matted hair, skin erythema). Conclusions: Everolimus significantly delayed mammary tumorigenesis in all five breast cancer mouse models. Our results suggest that everolimus is a promising cancer preventive drug for ER-negative tumors, and that further studies of everolimus in combination with other targeted therapies are warranted. In the future, clinical trials of the everolimus should be considered for the prevention of breast cancer in high-risk patients. Supported by NCI PREVENT Cancer Preclinical Drug Development Program (HHSN-2612015000-18I (PB). Citation Format: Abhijit Mazumdar, Jamal Hill, William Tahaney, Yanxia Ma, Alejandro Contreras, Shizuko Sei, Altaf Mohammed, Powel Brown. Targeting the mTOR pathway for the prevention of er-negative breast cancer [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 715.

The Possible Drug for Cancer and Metastasis Prevention

The Possible Drug for Cancer and Metastasis Prevention

Antioxidant and anti-Inflammation Potentials of Moringa oleifera Aqueous Extract Against breast cancer chemotherapy drug Induced Kidney and Liver Toxicity in Experimental Rats

Breast cancer is the most common causing death in women. Tamoxifen, 1-[4-(2-dimethyl-aminoethoxy) phenyl]-1,2-diphenyl-1-butene), is a nonsteroidal antiestrogen breast cancer prevention drug causing liver toxicity. This study was carried out to elucidate the efficacy of Moringa oleifera aqueous extract against carcinogenic effect of Tamoxifen in male rats. 50 male albino rats were divided equally into five groups: control group (I); Moringa oleifera aqueous group (II) of dose (300mg/Kg/day for 6 weeks); group (III) received Tamoxifen (3mg/Kg/3 days for 6 weeks); rats received orally Tamoxifen and Moringa oleifera aqueous extract together for 6 weeks group (IV) and rats pretreated with Moringa oleifera aqueous extract then Tamoxifen with the same dose and period group (V). In group (III) there were elevate in serum activities of ALT, AST, LDH, and serum levels of TNF-α, IL-1β, Il-10, cholesterol, TG, LDL, HDL, Urea, Creatinine also liver MDA; NO; ATPase. There were decrease in serum Total protein, Albumin and liver antioxidants markers (TAC and GSH) compared to control. In conclusion, oral administration of Moringa oleifera aqueous extract improved the biochemical markers and provided antioxidant activity against the toxicity of Tamoxifen in liver tissues.

Dual Blockade of Lactate/GPR81 and PD-1/PD-L1 Pathways Enhances the Anti-Tumor Effects of Metformin.

Metformin is a widely used antidiabetic drug for cancer prevention and treatment. However, the overproduction of lactic acid and its inefficiency in cancer therapy limit its application. Here, we demonstrate the synergistic effects of the lactate/GPR81 blockade (3-hydroxy-butyrate, 3-OBA) and metformin on inhibiting cancer cells growth in vitro. Simultaneously, this combination could inhibit glycolysis and OXPHOS metabolism, as well as inhibiting tumor growth and reducing serum lactate levels in tumor-bearing mice. Interestingly, we observed that this combination could enhance the functions of Jurkat cells in vitro and CD8+ T cells in vivo. In addition, considering that 3-OBA could recover the inhibitory effects of metformin on PD-1 expression, we further determined the dual blockade effects of PD-1/PD-L1 and lactate/GPR81 on the antitumor activity of metformin. Our results suggested that this dual blockade strategy could remarkably enhance the anti-tumor effects of metformin, or even lead to tumor regression. In conclusion, our study has proposed a novel and robust strategy for a future application of metformin in cancer treatment.

Cancer Preventive and Therapeutic Potential of Banana and Its Bioactive Constituents: A Systematic, Comprehensive, and Mechanistic Review

BackgroundThe banana (Musa spp.) plant produces elongated and edible fruit. The two main parthenocarpic species of banana are Musa accuminata Colla and Musa balbisiana Colla. There are several health-promoting and disease-preventing effects of Musa accuminata Colla, which are attributed to its important bioactive compounds, including phenolics, carotenoids, biogenic amines, phytosterols, and volatile oils, found in the stem, fruit, pseudostem, leaf, flower, sap, inner trunk, root, and inner core. Banana possesses numerous pharmacological activities, such as antioxidant, immunomodulatory, antimicrobial, antiulcerogenic, hypolipidemic, hypoglycemic, leishmanicidal, anthelmintic, and anticancer properties. Various individual studies have reported anticancer effects of different components of the banana plant. However, according to our understanding, an up-to-date, systematic, and critical analysis of existing scientific results has not yet been carried out.ObjectivesThis review aims to include a thorough assessment of banana and its phytochemicals for cancer prevention and therapy with a focus on cellular and molecular mechanisms of action.MethodsThe available research studies on anticancer activities of banana extracts, fractions and pure compounds were collected using various scholarly databases, such as PubMed, ScienceDirect, and Scopus, based on predetermined selection criteria.ResultsVarious banana extracts, fractions, and phytoconstituents, including ferulic acid, protocatechualdehyde, 2-pentanone, 4-epicyclomusalenone, cycloeucalenol acetate, and chlorogenic acid, have been shown to exhibit cancer preventative and anticancer activities in breast, cervical, colorectal, esophageal, hepatic, oral, prostate, and skin cancers. Bioactive components present in bananas have exhibited antiproliferative, cell cycle arrest-inducing, apoptotic, anti-adhesive, anti-invasive, and antiangiogenic effects through modulation of diverse, dysregulated oncogenic signaling pathways.ConclusionBased on the critical analysis of available literature, banana products and phytoconstituents show enormous potential for future development of drugs for cancer prevention and therapy. However, more mechanistic studies and well-designed clinical trials should be performed to establish its efficacy.

Synthesis and studies of acetylthioglycoside conjugates of 4-chloro-1,2-dithiole-3-thione as potential antitumor agents

Nucleophilic substitution of a chlorine atom in 4,5 dichloro-1,2-dithiole-3-thione with per-O-acetyl-1-mercaptho derivatives of d-glucose, d-galactose, d-mannose, d-xylose, l-arabinose, and d-maltose gave six new acetylthioglycoside conjugates of 4-chloro-1,2-dithiole-3-thione. These thioglycosides were shown to possess cancer preventive activity on the models of JB6 Cl41 P+ mouse epidermal cells and THP-1 human leukemia cells in soft agar, as well as to inhibit the AP-1-dependent transcriptional activity in JB6 Cl41 luc-AP-1 cells, which suggests the possibility of using the new compounds as potential cancer preventive drugs.

Targeting CDK12 for Cancer Therapy: Function, Mechanism, and Drug Discovery.

Cyclin-dependent kinase 12 (CDK12) is a member of the CDK family of proteins (CDK) and is critical for cancer development. Years of study into CDK12 have generated much information regarding the intricacy of its function and mechanism as well as inhibitors against it for oncological research. However, there remains a lack of understanding regarding the role of CDK12 in carcinogenesis and cancer prevention. An exhaustive comprehension of CDK12 will highly stimulate the development of new strategies for treating and preventing cancer. Here, we review the literature of CDK12, with a focus on its function, its role in signaling, and how to use it as a target for discovery of novel drugs for cancer prevention and therapy.

An Overview of Cancer Prevention: Chemoprevention and Immunoprevention

Cancer prevention encompasses a broad spectrum of strategies designed to lower the chance of developing cancer and reduce the morbidity of established cancer. There are three levels of cancer prevention. Eliminating or mitigating cancer risk factors by adopting healthy behaviors and lifestyles, such as avoiding tobacco and alcohol use, exercising, eating a healthy diet, and applying sunscreen to protect against UV exposure, belongs to primary prevention and is the easiest and most effective way of preventing cancer for the general public. Secondary prevention includes screening to identify precancerous lesions and taking intervention measures to prevent disease progression to malignancy. Tertiary prevention refers to reducing or controlling the symptoms and morbidity of established cancer or the morbidity caused by cancer therapy. For high-risk populations, chemopreventive agents, such as selective estrogen receptor modulators (including tamoxifan and raloxifene) in breast cancer prevention and non-steroidal anti-inflammatory drugs (aspirin) in colorectal cancer prevention, and immunoprevention using human papillomavirus and hepatitis B virus vaccines in infection-related cancers have shown clear clinical benefits of reducing cancer incidences. In this review, we will summarize the current status of cancer prevention, focusing on the major agents that are clinically used for chemoprevention and immunoprevention.

Abstract 1855: Statins decrease the expression of c myc in cancer cell lines

Abstract The widely used statin drugs for the prevention of cardiovascular diseases are envisioned to have the potential to control cancer. Repurposing these cardiovascular drugs for cancer prevention and/or treatment is an attractive proposition as these drugs are commonly prescribed in the clinic. However, there was no clinical evidence for statins being used as chemopreventive agents and the reasons for this are unclear. To further establish the effectiveness of statins as chemopreventive agents, we investigated the effects of three most common statins, simvastatin, atorvastatin and lovastatin on six different cancer cell lines including an ovarian cancer cell line that overexpresses P-glycoprotein, an ABCB1 gene product. Incubation of cells with statins (at both 12.5 microM and 25 microM) resulted in decreased cell growth in a time-dependent manner. The decreased cell growth could be correlated with decreased cellular NADPH levels. Measurement of viable and dead cells in statin treatments indicated that statins induced cell proliferation arrest without inducing cell death. Removal of statins from culture medium resulted in robust cell growth, identical to that observed in controls. Further, cell cycle analysis clearly indicated that statins induced cell cycle arrest at G0/G1 phase without inducing apoptosis. Analysis of the mechanism of statins in these cancer cells indicated that these drugs inhibit HMG CoA reductase, without affecting the transcript of the HMGCR. The HMG CoA reductase inhibition could be relieved with mevalonate. Analysis of key target proteins important for cancer cell proliferation identified that exposure of cancer cells to statins significantly decreased c-Myc protein without affecting its transcription. Importantly, removal of statins reversed the c-Myc expression to the normal level. Finally, incubation of cells with statins increased phosphorylation of H2AX, suggesting that statins promote cellular senescence. These data together suggested that statins are cytostatic, and eliminate c-Myc expression. These observations are consistently observed in the multidrug-resistant cells as well. These data lend strong support that statins could serve as excellent agents for cancer chemoprevention. Citation Format: U.S. Rao, Randy Mullins, Prema Rao. Statins decrease the expression of c myc in cancer cell lines [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1855.