Cancer Chemoprevention Research Articles

Abstract A022: Limonene as a vehicle in topical delivery of carvedilol for skin cancer chemoprevention

Abstract Skin cancer is currently one of the most common cancers and is defined as an abnormal growth of the skin cells. The goal of this study is to develop a topical delivery system of carvedilol with limonene as the vehicle. Limonene is a major component found in the rinds of citrus fruits and other herbs. It is one of many natural compounds that have demonstrated inhibitory activity in different types of cancers such as breast, lung, and stomach cancer. Furthermore, limonene has shown to increase skin permeation of drugs including carvedilol. The soft agar colony formation assay was used to evaluate anchorage-independent growth of JB6 mouse epidermal cells. This assay tested concentrations of carvedilol (0.1, 1.0 and 10 μM); limonene (1.0, 10, 100 and 1000 μM); and a combination of carvedilol (1.0 μM) and limonene (1.0, 10 or 100 μM). Results demonstrated that carvedilol and limonene as single treatment inhibited colony formation. The combination of carvedilol and limonene showed higher colony inhibition than single treatment, although not statistically significant. Franz diffusion cell was used to test for permeation of the drug. The device has two chambers separated by a membrane, which in this case is rat skin. The drugs, in vehicles of 40% polyethylene glycol (PEG) 400 in PBS or 40% PEG400 in PBS plus 5% limonene were applied into the donor chamber while the samples are collected through the receptor chamber as the drug permeates through the skin. The samples were collected at 16 hours, 20 hours, and 24 hours. Results showed that limonene significantly increased permeation. Therefore, our data indicate that limonene was able to increase skin permeation and the chemopreventive activity of carvedilol. This new formulation will be further examined in animal models for its efficacy against UV-induced skin cancer. Citation Format: Janell Wang, Lawrence Chao, Steven Yeung, Ying Huang. Limonene as a vehicle in topical delivery of carvedilol for skin cancer chemoprevention [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 A022.

Abstract IA005: Discovery and development of LFA-9 for CRC prevention

Abstract Colorectal Cancer (CRC) is a major public health issue with an estimated 980,000 deaths annually, worldwide. Current trends show an increase of CRC incidence and mortality worldwide. Colonic adenomas are very common in ages 50 and over. Though, nonsteroidal antiinflammatory agents like Aspirin, Naproxen and COX-2 inhibitor and Celecoxib are useful to prevent the polyp progression and reducing CRC burden, continuous/chronic usage of these drugs are limited by GI toxicity and unwanted side effects. Thus, the rationale to establish safer anti-inflammatory agents for CRC prevention is important. Mechanistic studies suggest that up-regulation of 15-PGDH, sparing COX-1/2 and prostaglandin (PG)I2 synthase and/or selectively targeting mPGES-1 and 5-LOX would reduce the cardiovascular side effects and may improve the chemopreventive efficacy. There are limited to no studies on targeting mPGES-1/5LOX and it is one of the unexplored areas in colorectal cancer chemoprevention towards safer drug development. To design and develop selective inhibitors of dual mPGES-1/5-LOX, we used in-silico small molecular docking simulation approaches, and identified LFA-9 as a novel duel mPGES-1/5-LOX inhibitor among >35 analogs. Azoxymethane (AOM)-induced rat colonic tumors were utilized as ex-vivo to assess pharmacodynamic inhibitory effects of LFA-9 on mPGES-1 and 5-LOX by Radio-HPLC. In a series of animal experiments, we established the dose-range of toxicity and optimal doses of LFA-9. Potential preventive efficacy of LFA-9 was assessed AOM-rat colon carcinogenesis (Aberrant Crypt Foci, (ACF) as surrogate marker in male F344 rats and intestinal tumor inhibition in APCMin/+ mice. Furthermore, we have shown the efficacy of LFA-9 administered in the diet at the adenoma stage significantly suppressed colonic adenocarcinoma formation in AOM-induced colon cancer (sporadic CRC model) and PIRC rat model (FAP model). Overall, the above results show that LFA-9, a novel dual mPGES-1/5-LOX inhibitor, is a safer agent and has potential for prevention of CRC in high-risk patients. {This work was supported by NCI-PREVENT Cancer Program, R01 CA213987 and VA Merit Awards} Citation Format: Chinthalapally V. Rao. Discovery and development of LFA-9 for CRC prevention [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 IA005.

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.

Effects of saffron and its active constituent crocin on cancer management: A narrative review.

Cancer is a major public health problem in the world, and it dramatically affects the life expectancy of patients and their quality of life. Natural products from botanicals could be beneficial in the prevention or treatment of a variety of cancers. Saffron (the extract of Crocus sativus) includes its major constituent, crocin, have been used as a folk medicine for a long time, and they have shown obvious cancer chemoprevention potential. The objectives of this review are to present the progress of research on the effects of saffron and crocin in cancer management and the underlying mechanisms of action. We searched publications in the English language, published between January 1, 1980 and September 30, 2022, of saffron and crocin on cancer through several search engines, i.e., PubMed, SciFinder and Web of Science. In this article, we first summarize the phytochemical studies of this botanical. Then, we present the anticancer effects of saffron and crocin on different human cancer cells. Saffron and crocin showed obvious antiproliferative effects on human cancer cell lines, including colorectal cancer, breast cancer, lung cancer, prostate cancer, cervical cancer, leukemia, glioblastoma and rhabdomyosarcoma. Finally, the anticancer-related mechanisms of action are summarized, including cell cycle arrest at G0/G1 or G2/M phases, induction of caspase-dependent apoptosis, signaling pathway-linked tumor metabolism regulation, and adaptive immunity regulated inflammation of host immune responses. Previous studies related to saffron and crocin in cancer management have been reviewed and reported results have been analyzed. Clinical data suggest that saffron and crocin have beneficial effects to improve quality of life in cancer patients. Thus, saffron and crocin can be considered promising candidates for future clinical cancer studies.

IN SILICO MOLECULAR DOCKING STUDIES OF OVARIAN EXTRACT SINGKARAK LAKE PUFFERFISH (TETRAODON LEIURUS) AGAINST BREAST CANCER

Targets the development of breast cancer chemoprevention by blocking the expression of NaV 1.5 channels and NHE, decreasing the expression of Bcl-2 and Bcl-XL, and increasing the expression of Bax. The ovarian extract Singkarak Lake Pufferfish (Tetraodon leiurus) has the potential as chemoprevention in breast cancer cell lines (MCF-7). This study aimed to analyze the interaction of STX, neoSTX, and dcSTX ligands against NaV1.5, NHE, Bcl-2, Bcl-XL, and Bax receptors. This study used the molecular docking method using STX, neoSTX, and dcSTX ligands against NaV1.5, NHE, Bcl-2, Bcl-XL, and Bax receptors. The result showed that the STX ligand has a more stable interaction with NaV1.5, Bcl-2, Bcl-XL, and Bax receptors with ΔG values of -8.72, -7.32 -6.86, and -6.31 kcal/mol compared to neoSTX and dcSTX ligands. Furthermore, the neoSTX ligand has a more stable interaction with the NHE receptor with an ΔG value of -7.5 kcal/mol compared to the STX and dcSTX ligands. This study shows that the ovarian extract of Singkarak Lake Pufferfish (Tetraodon leiurus) has the potential to be developed as cancer chemoprevention.

Emerging current trends and research focus related to pancreatic cancer metabolism: A bibliometric and visualized analysis.

As a malignant digestive system tumor, pancreatic cancer has unique metabolic characteristics. In recent years, the study of pancreatic cancer metabolism is in full swing, which provides a new direction for the treatment of pancreatic cancer patients. However, there is no systematic report of pancreatic cancer metabolism. In this paper, bibliometrics and visualization methods were used to analyze the number of publications, countries/regions, authors, institutions, journals, co-cited references, and keywords of pancreatic cancer metabolism articles, to summarize the research trends and predict research hotspots. We searched, screened and downloaded articles on pancreatic cancer metabolism through the Web of Science Core Collection (WoSCC). Using CiteSpace, VOSviewer and Bibliometrix Package to analyze publications, countries/regions, authors, institutions, journals, co-cited references, and keywords of pancreatic cancer metabolism to identify research trends and predict research hotspots. According to the inclusion and exclusion criteria, a total of 5,255 articles were retrieved during the period 1943-2022. The number of publications on pancreatic cancer metabolism is increasing year by year. The United States (n=1602, 30.49%), China (n=1074, 20.44%), and Italy (n=313, 5.96%) are the three countries with the largest number of publications and citations, and there is close cooperation between countries. LI J (n=55) is the most prolific author. FUDAN UNIV (n=348) is the most published institution. CANCERS (n=118), PLOS ONE (n=93), and CANCER RESEARCH (n=80) are the most popular journals in this field. "Nutriment-deficient environment", "cancer chemoprevention" and "targeting cancer stem cell" are the main areas of focus. "immunotherapy", "ferroptosis" and "targeted therapy" are hot keywords in recent years. Taking pancreatic cancer metabolism as an entry point to study the role of traditional Chinese medicine (TCM) mainly focuses on curcumin and resveratrol, lack of broader and deeper research on TCM. The number of publications on pancreatic cancer metabolism has generally increased, and scholars have generally paid more attention to this field. "immunotherapy", "ferroptosis" and "targeted therapy" are the current research hotspots. The in-depth study of pancreatic cancer metabolism will provide new ideas for the treatment of pancreatic cancer.

Phytochemical Targeting of Mitochondria for Breast Cancer Chemoprevention, Therapy, and Sensitization.

Breast cancer is a common and deadly disease that causes tremendous physical, emotional, and financial burden on patients and society. Early-stage breast cancer and less aggressive subtypes have promising prognosis for patients, but in aggressive subtypes, and as cancers progress, treatment options and responses diminish, dramatically decreasing survival. Plants are nutritionally rich and biologically diverse organisms containing thousands of metabolites, some of which have chemopreventive, therapeutic, and sensitizing properties, providing a rich source for drug discovery. In this study we review the current landscape of breast cancer with a central focus on the potential role of phytochemicals for treatment, management, and disease prevention. We discuss the relevance of phytochemical targeting of mitochondria for improved anti-breast cancer efficacy. We highlight current applications of phytochemicals and derivative structures that display anti-cancer properties and modulate cancer mitochondria, while describing future applicability and identifying areas of promise.

Lung protective effects of dietary malate esters derivatives from Bletilla striata against SiO2 nanoparticles through activation of Nrf2 pathway

ObjectiveTo study the protective activities of the dietary malate esters derivatives of Bletilla striata against SiO2 nanoparticles-induced A549 cell lines and its mechanism action. MethodsThe components were isolated and elucidated by spectroscopic methods such as 1D NMR and 2D NMR. And MTT assays was used to tested these components on the A549 cell survival rates and ROS or proteins levels were detected by Western blotting. ResultsA new glucosyloxybenzyl 2-isobutylmalate (a malate ester derivative), along with 31 known compounds were isolated and identified from n-BuOH extract of EtOH extract of B. striata. Among them, compounds 3, 4, 11, 12 and 13 possessed noteworthy proliferative effects for damaged cells, with ED50 of 14.0, 13.1, 3.7, 11.6 and 11.5 µmol/L, respectively, compared to positive control resveratrol (ED50, 14.7 µmol/L). Militarine (8) prominently inhibited the intracellular ROS level, and increased the expression of Nrf2 and its downstream genes (HO-1 and γ-GCSc). Furthermore, Nrf2 activation mediates the interventional effects of compound 8 against SiO2 nanoparticles (nm SiO2)-induced lung injury. Moreover, treatment with compound 8 significantly reduced lung inflammation and oxidative stress in nm SiO2-instilled mice. Molecular docking experiment suggested that 8 bound stably to the HO-1 protein by hydrogen bond interactions. ConclusionThe dietary malate esters derivatives of B. striata could significantly increase the viability of nm SiO2-induced A549 cells and decrease the finer particles-induced cell damages. Militarine is especially promising compound for chemoprevention of lung cancer induced by nm SiO2 through activation of Nrf2 pathway.

Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer

A leading theory for ovarian carcinogenesis proposes that inflammation associated with incessant ovulation is a driver of oncogenesis. Consistent with this theory, nonsteroidal anti-inflammatory drugs (NSAIDs) exert promising chemopreventive activity for ovarian cancer. Unfortunately, toxicity is associated with long-term use of NSAIDs due to their cyclooxygenase (COX) inhibitory activity. Previous studies suggest the antineoplastic activity of NSAIDs is COX independent, and rather may be exerted through phosphodiesterase (PDE) inhibition. PDEs represent a unique chemopreventive target for ovarian cancer given that ovulation is regulated by cyclic nucleotide signaling. Here we evaluate PDE10A as a novel therapeutic target for ovarian cancer. Analysis of The Cancer Genome Atlas (TCGA) ovarian tumors revealed PDE10A overexpression was associated with significantly worse overall survival for patients. PDE10A expression also positively correlated with the upregulation of oncogenic and inflammatory signaling pathways. Using small molecule inhibitors, Pf-2545920 and a novel NSAID-derived PDE10A inhibitor, MCI-030, we show that PDE10A inhibition leads to decreased ovarian cancer cell growth and induces cell cycle arrest and apoptosis. We demonstrate these pro-apoptotic properties occur through PKA and PKG signaling by using specific inhibitors to block their activity. PDE10A genetic knockout in ovarian cancer cells through CRISP/Cas9 editing lead to decreased cell proliferation, colony formation, migration and invasion, and in vivo tumor growth. We also demonstrate that PDE10A inhibition leads to decreased Wnt-induced β-catenin nuclear translocation, as well as decreased EGF-mediated activation of RAS/MAPK and AKT pathways in ovarian cancer cells. These findings implicate PDE10A as novel target for ovarian cancer chemoprevention and treatment.

Identification of natural product 3, 5-diiodotyrosine as APOBEC3B inhibitor to prevent somatic mutation accumulation and cancer progression

BackgroundThe development of cancer is largely dependent on the accumulation of somatic mutations, indicating the potential to develop cancer chemoprevention agents targeting mutation drivers. However, ideal cancer chemoprevention agents that...

Conformationally Defined Rexinoids for the Prevention of Inflammation and Nonmelanoma Skin Cancers.

Compound 1 is a potent rexinoid that is highly effective in cancer chemoprevention but elevates serum triglycerides. In an effort to separate the lipid toxicity from the anticancer activity of 1, we synthesized four new analogs of rexinoid 1, of which three rexinoids did not elevate serum triglycerides. Rexinoids 3 and 4 are twice as potent as rexinoid 1 in binding to Retinoid X receptor (RXR). All-trans retinoic acid (ATRA) plays a key role in maintaining skin homeostasis, and rexinoids 3-6 are highly effective in upregulating the genes responsible for the biosynthesis of ATRA. Inflammation plays a key role in skin cancer, and rexinoids 3 and 4 are highly effective in diminishing LPS-induced inflammation. Rexinoids 3 and 4 are highly effective in preventing UVB-induced nonmelanoma skin cancer (NMSC) without displaying any overt toxicities. Biophysical studies of rexinoids 3 and 5 bound to hRXRα-ligand binding domain (LBD) reveal important conformational and dynamical differences in the ligand binding domain.

Development of Genistein Drug Delivery Systems Based on Bacterial Nanocellulose for Potential Colorectal Cancer Chemoprevention: Effect of Nanocellulose Surface Modification on Genistein Adsorption

Genistein is an isoflavone with antioxidant, anti-inflammatory, and anticancer properties. That said, its use in the industry is limited by its low solubility in aqueous systems. In this work, bacterial nanocellulose (BNC) and BNC modified with cetyltrimethylammonium (BNC-CTAB) were evaluated as genistein-encapsulating materials for their controlled release in cancer chemoprevention. Thin films were obtained and characterized by contact angle, AFM, TEM, UV-Vis spectroscopy FTIR, and TGA techniques to verify surface modification and genistein encapsulation. The results show a decrease in hydrophilization degree and an increase in diameter after BNC modification. Furthermore, the affinity of genistein with the encapsulating materials was determined in the context of monolayer and multilayer isotherms, thermodynamic parameters and adsorption kinetics. Spontaneous, endothermic and reversible adsorption processes were found for BNC-GEN and BNC-CTAB-GEN. After two hours, the maximum adsorption capacity corresponded to 4.59 mg GEN∙g-1 BNC and 6.10 mg GEN∙g-1 BNC-CTAB; the latter was a more stable system. Additionally, in vitro release assays performed with simulated gastrointestinal fluids indicated controlled and continuous desorption in gastric and colon fluids, with a release of around 5% and 85%, respectively, for either system. Finally, the IC50 tests made it possible to determine the amounts of films required to achieve therapeutic concentrations for SW480 and SW620 cell lines.

Evaluation of the Effects of Genistein In Vitro as a Chemopreventive Agent for Colorectal Cancer-Strategy to Improve Its Efficiency When Administered Orally.

Colorectal Cancer (CRC) ranks third in terms of incidence and second in terms of mortality and prevalence worldwide. In relation to chemotherapy treatment, the most used drug is 5-fluorouracil (5-FU); however, the use of this drug generates various toxic effects at the systemic level. For this reason, new therapeutic strategies are currently being sought that can be used as neoadjuvant or adjuvant treatments. Recent research has shown that natural compounds, such as genistein, have chemotherapeutic and anticancer effects, but the mechanisms of action of genistein and its molecular targets in human colon cells have not been fully elucidated. The results reported in relation to non-malignant cell lines are also unclear, which does not allow evidence of the selectivity that this compound may have. Therefore, in this work, genistein was evaluated in vitro in both cancer cell lines SW480 and SW620 and in the non-malignant cell line HaCaT. The results obtained show that genistein has selectivity for the SW480 and SW620 cell lines. In addition, it inhibits cell viability and has an antiproliferative effect in a dose-dependent manner. Increased production of reactive oxygen species (ROS) was also found, suggesting an association with the cell death process through various mechanisms. Finally, the encapsulation strategy that was proposed made it possible to demonstrate that bacterial nanocellulose (BNC) is capable of protecting genistein from the acidic conditions of gastric fluid and also allows the release of the compound in the colonic fluid. This would allow genistein to act locally in the mucosa of the colon where the first stages of CRC occur.

Multi-unit pellet drug delivery system of Danggui Decoction extracts for chemoprevention of IBD-associated colorectal cancer in rats

Anti-inflammation has become pivotal in chemoprevention of inflammatory bowel disease (IBD)-associated colorectal cancer (CRC). The chemopreventive effects of anti-inflammatory drugs currently used in IBD therapy are still not clear based on existing epidemiological studies. Therefore, novel chemopreventive candidates need to be investigated and natural products derived from food as well as complementary and alternative medicine have become attractive resources with advantages including multi-components and multi-targets. Danggui Decoction (DGD), composed of Angelicae Sinensis Radix, Zingiberis Recens Rhizoma and Jujubae Fructus, is a traditional Chinese medicinal formula for the treatment of IBD, and DGD supercritical fluid extracts (DGDSFE) as well as DGD polysaccharide extracts (DGDPE) are potential effective constituents for chemoprevention. This article constructed a multi-unit pellet drug delivery system (MUPDDS) containing two independent parts, DGDSFE colon-targeted pellets and DGDPE pellets, according to the different characteristics of extracts, by applying extrusion-spheronization and coating technology. The chemopreventive effect of this MUPDDS was evaluated in the rat model induced by 1,2-dimethylhydrazine and dextran sulfate sodium. The tumor incidence, tumor number and tumor volume were reduced after the administration of MUPDDS daily for 14 weeks, with serum levels of TNF-α, IL-1β and hepcidin decreased and levels of IFN-γ and IL-2 in splenocyte supernatant elevated, indicating anti-inflammation, iron metabolism regulation and immune regulation of DGDSFE and DGDPE in MUPDDS. Furthermore, the feasibility and advantage of MUPDDS in chemoprevention was displayed by compared with extracts, DGDSFE colon-targeted pellets or DGDPE pellets, providing an inspiring strategy to achieve better effect of traditional Chinese medicines in cancer prevention.

Part 4: Scientific sunburn & skin cancer

Part 4: Scientific sunburn & skin cancer Chanda Siddoo-Atwal, President and Primary Biochemist of Moondust Cosmetics Ltd, looks at resveratrol as a solution to skin cancer through sunburn and summer sun exposure. Analysing tumour formation and the apoptosis of cells, this plant compound, resveratrol can restrict abnormal tumour growth through a simple topical application. In this last of a four part series, Chanda Siddoo-Atwal, explores the potential of the plant compound, resveratrol, as a cancer chemopreventive agent in the context of sunburn & skin cancer.

An Aspirin a Day: New Pharmacological Developments and Cancer Chemoprevention.

Chemoprevention refers to the use of natural or synthetic agents to reverse, suppress, or prevent the progression or recurrence of cancer. A large body of preclinical and clinical data suggest the ability of aspirin to prevent precursor lesions and cancers, but much of the clinical data are inferential and based on descriptive epidemiology, case control, and cohort studies or studies designed to answer other questions (e.g., cardiovascular mortality). Multiple pharmacological, clinical, and epidemiologic studies suggest that aspirin can prevent certain cancers but may also cause other effects depending on the tissue or disease and organ site in question. The best-known biological targets of aspirin are cyclooxygenases, which drive a wide variety of functions, including hemostasis, inflammation, and immune modulation. Newly recognized molecular and cellular interactions suggest additional modifiable functional targets, and the existence of consensus molecular cancer subtypes suggests that aspirin may have differential effects based on tumor heterogeneity. This review focuses on new pharmacological developments and innovations in biopharmacology that clarify the potential role of aspirin in cancer chemoprevention.

Systemic and Anticancer Potential of Adaptogenic Constituents Isolated from Traditional Herbs - A Mini-Review.

Adaptogens were initially recognized as stress-resistance inducing compounds. Recent studies reveal that adaptogens are pleiotropically-acting chemical constituents that can be isolated from traditional herbs. They are gaining increasing attention in cancer chemotherapy. This review summarizes the physiological action of adaptogens isolated from the 9 most widely used traditional herbs implicated in cancer therapy viz., Withania somnifera, Tinospora cordifolia, Rhodiola rosea, Emblica officinalis, Glycyrrhiza glabra, Bacopa monnieri, Asparagus racemosus, Ocimum sanctum, and Panax notoginseng. The studies were identified through a systematic search of major computerized databases such as Pubmed, Embase, Medline, Inflibnet, Google Scholar, and Cochrane Library. Individual names of each herb and biological action were the search terms employed. In this review, we have enlisted the chemical constituents and their mechanism of action in a few organ systems as well as in cancer cells. Studies indicate that the adaptogens isolated from these herbs can be broadly arranged into 2 classes based on their chemical structure. These molecules exert a positive influence on several organ systems such as respiratory, nervous, cardiovascular, immune, and gastrointestinal tracts. It is also clear that adaptogens act as effective chemopreventive agents alone or in combination with chemo drugs in multiple cancers by targeting multiple intracellular target proteins. Therefore, we conclude that adaptogens are versatile ligands capable of eliciting many systemic effects. Their biological functions are complex, varied, and context-dependent in various cancers. This offers great scope for personalized treatment and cancer chemoprevention in the future.

Back Cover: Modification of Diet to Reduce the Stemness and Tumorigenicity of Murine and Human Intestinal Cells

Mol. Nutr. Food Res. 2022, 66, 202200234 DOI: 10.1002/mnfr.202200234 Black raspberries (BRBs) play a role in colorectal cancer chemoprevention. The number of intestinal stem cells, the cells of origin of colorectal cancer, are reduced following a BRB diet. This decreases the chance of a mutation occurring within these stem cells and subsequently reduces the risk of developing colorectal cancer. This is reported by Stephanie May, Lee Parry, and co-workers in article number 2200234.

EXPRESSION OF BCL-2 AND BAX GENES INDUCED BY AN OVARIAN EXTRACT OF SINGKARAK LAKE PUFFERFISH (Tetraodon leiurus) IN BREAST CANCER CELL

It is known that the ovarian extract of Singkarak Lake Pufferfish (Tetraodon leiurus) has the potential for chemoprevention in MCF-7 cells. However, the expression of Bcl-2 and Bax genes was associated with cancer. Therefore, this study aimed to analyze the Bcl-2 and Bax gene expression induced by the ovarian extract of Singkarak Lake Pufferfish (Tetraodon leiurus) in MCF-7. The method in this study was an in vitro experiment using MCF-7 control cells and MCF-7 cells induced by the ovarian extract of Singkarak Lake Pufferfish (Tetraodon leiurus), and Real-time PCR was used to examine the expression of Bcl-2 and Bax genes. The result showed that the expression of the Bcl-2 gene had an insignificant decrease (p>0.05) by 15%, and the expression of the Bax gene had a significant increase (p<0.05) by 489% compared to the control. These results support that ovarian extract Singkarak Lake Pufferfish (Tetraodon leiurus) can be alternative cancer chemoprevention.

Promising Phyto-Antioxidant Methanolic Extract from Canarium Odontophyllum Miq. (Dabai) Leaves against UVB Induced B164A5 Melanoma Cells as a Potential Skin Chemoprevention Agent

The high incidence and mortality of skin cancer along with the development of chemotherapy resistance have urged researchers to look into alternative strategies to combat cancer. Chemoprevention is one of the well-researched strategies using natural products. Canarium odontophyllum Miq. (dabai) is a local seasonal fruit that is mainly found in Sarawak, Malaysia. The leaves of the fruit harbor many medicinal useful phytochemicals that provide a new insight for chemoprevention. The present research has been planned to study the chemopreventive activity of methanolic extract of C. odontophyllum Miq. leaves on UVB induced B164A5 melanoma cells through its antioxidant profiles. The extract displayed statistically significant (p<0.05) antioxidant activity by enhancing superoxide dismutase, SOD (1023.02 ± 106.74 U/mg protein) and catalase (0.12 ± 0.003 U/mg protein) activities compared to negative control. Low oxidative damage was also observed whereby the protein carbonyl and malondialdehyde levels were significantly reduced (p<0.05), 1.69 ± 0.296 nmol/mg protein and 1.181 ± 0.03 nmol/mg protein respectively. In conclusion, the extract exhibited a promising skin cancer chemoprevention activity through its significant antioxidant activities. These findings evidently pave the path for further investigations in chemoprevention strategy.