Curcumin piperidone derivatives induce caspase-dependent apoptosis and suppress miRNA-21 expression in LN-18 human glioblastoma cells.

BACKGROUND: Previously, we have reported on the two curcuminoid analogues with piperidone derivatives, namely FLDP-5 and FLDP-8 have more potent anti-proliferative and anti-migration effects than curcumin. In this study, we further investigated the mode of cell death and the mechanism involved in the cell death process induced by these analogues on human glioblastoma LN-18 cells. RESULTS: The FLDP-5 and FLDP-8 curcuminoid analogues induced LN-18 cell death through apoptosis in a concentration-dependent manner following 24 h of treatment. These analogues induced apoptosis in LN-18 cells through significant loss of mitochondrial mass and mitochondrial membrane potential (MMP) as early as 1-hour of treatment. Interestingly, N-acetyl-l-cysteine (NAC) pretreatment did not abolish the apoptosis induced by these analogues, further confirming the cell death process is independent of ROS. However, the apoptosis induced by the analogues is caspases-dependent, whereby pan-caspase pretreatment inhibited the curcuminoid analogues-induced apoptosis. The apoptotic cell death progressed with the activation of both caspase-8 and caspase-9, which eventually led to the activation of caspase-3, as confirmed by immunoblotting. Moreover, the existing over-expression of miRNA-21 in LN-18 cells was suppressed following treatment with both analogues, which suggested the down-regulation of the miRNA-21 facilitates the cell death process. CONCLUSION: The FLDP-5 and FLDP-8 curcuminoid analogues downregulate the miRNA-21 expression and induce extrinsic and intrinsic apoptotic pathways in LN-18 cells.

Cellular and DNA Toxicity Study of Triphenyltin Ethyl Phenyl Dithiocarbamate and Triphenyltin Butyl Phenyl Dithiocarbamate on K562, Leukemia Cell Line.

INTRODUCTION: Continuous research for new effective drugs to treat cancer has improved our understanding on the mechanism of action of these drugs and paved new potential for their application in cancer treatments. In this study, organotin compounds known as triphenyltin ethyl phenyl dithiocarbamate and triphenyltin butyl phenyl dithiocarbamate were investigated for their toxicity on leukemia cell line (K562) and non-cancerous cell line (Chang liver cell and lung fibroblast, V79 cell). METHODS: MTT assay was performed to evaluate the cytotoxic effects of both compounds toward the cells after 24, 48 and 72 hours of exposure or treatment. The alkaline comet assay was conducted to determine the DNA damage on K562 cells after been exposed to both compounds for 30, 60 and 90 minutes. RESULTS: The IC50 values obtained from K562 cells ranged from 0.01 to 0.30 µM, whereas for both Chang liver cell and lung fibroblast V79 cell, the values ranged from 0.10 to 0.40 µM. For genotoxicity evaluation, the percentage of damaged DNA is measured as an average of tail moment, and was found to be within 1.20 to 2.20 A.U while the percentage of DNA intensity ranging from 1.50 to 3.50% indicating no genotoxic effects. CONCLUSION: Both compounds are cytotoxic toward leukemia cells and non-cancerous cells but do not exert their genotoxic effects towards leukemia cell.

Genoprotective potential of Macaranga species phytochemical compounds on HT-29 human colorectal adenocarcinoma cell line.

BACKGROUND: The species of genus Macaranga are widely found in Malaysian secondary forests and has been used as an alternative for treating varieties of illness. Studies have shown that the medicinal properties of this genus contain anti-inflammatory, antioxidant, and anti-cancer effects. This study aimed to determine the cytotoxicity of six isolated phytochemicals from Macaranga heynei (M. heynei), Macaranga lowii and Shorea leprosula on HT-29 human colorectal adenocarcinoma cell lines. RESULTS: One out of six isolated phytochemical compounds, identified as "Laevifolin A", showed a cytotoxicity with an IC50 value of 21.2 µM following 48 h treatment as detected using Sulforhodamine B (SRB) assay. Additionally, no induction of apoptosis and oxidative stress were observed on Laevifolin A treated HT-29 cells as determined using Annexin V-FITC/PI assay and dihydroethidine (HE) staining, respectively. Additionally, no damage to the DNA were observed as measured using the Alkaline Comet assay. Further investigation on menadione-induced oxidative DNA damage showed the genoprotective potential of Laevifolin A on HT-29 cells. CONCLUSIONS: In conclusion, this study indicated that only one compound (Laevifolin A) that extracted from M. heynei has the cytotoxicity potential to be developed as an anticancer agent in human colorectal adenocarcinoma. However, besides exhibiting cytotoxic effect, the compound also exhibits genoprotective capability that warrant further investigation.

The Effects of 12 Weeks Colostrum Milk Supplementation on the Expression Levels of Pro-Inflammatory Mediators and Metabolic Changes among Older Adults: Findings from the Biomarkers and Untargeted Metabolomic Analysis.

Senescence is a normal biological process that is accompanied with a series of deteriorations in physiological function. This study aimed to investigate the effects of bovine colostrum milk supplementation on metabolic changes and the expression of various biomarkers on inflammation, antioxidant and oxidative damage, nutrient metabolism, and genomic stability among older adults. Older adults (50-69 years old) who participated in the 12-week randomized, double-blinded, placebo-controlled trial were instructed to consume the IgCo bovine colostrum-enriched skim milk or regular skim milk (placebo) twice daily. Following 12 weeks of intervention, participants in the intervention group had lower expression levels in pro-inflammatory mediators (CRP, IL-6, and TNF-α), with significant (p < 0.05) interaction effects of the group and time observed. However, no significant interaction effect was observed in the vitamin D, telomerase, 8-OHdG, MDA, and SOD activities. UPLC-MS-based untargeted metabolomics analysis revealed that 22 metabolites were upregulated and 11 were downregulated in the intervention group compared to the placebo group. Glycerophospholipid metabolism, along with cysteine and methionine metabolism were identified as the potential metabolic pathways that are associated with bovine colostrum milk consumption. In conclusion, consuming bovine colostrum milk may induce metabolic changes and reduce the expression of various pro-inflammatory mediators, thus improving the immune function in older adults.

The potential roles of lncRNA TINCR in triple negative breast cancer.

Triple negative breast cancer (TNBC) is the most aggressive intrinsic breast cancer subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and low levels of human epidermal growth factor receptor 2 (HER2). The complex nature of TNBC has resulted in little therapeutic progress for the past several decades. The standard of care remains the FEC cocktail (5-fluorouracil (5-FU), epirubicin and cyclophosphamide). However, early relapse and metastasis in TNBC patients persists in causing dismal clinical outcomes. Due to complex heterogeneity features of TNBC, identifying the biomarker associated to the chemoresistance remains a challenge. The emergence of the long non-coding RNA (lncRNA) as a potential signature may have proven to be a new deterrent to diagnostic and treatment options. Previous studies unveiled the associations of lncRNA in the development of TNBCs whereby the aggressiveness and response to therapies may be associated by the abrogation of the molecular mechanism lncRNA. Terminal differentiation induced ncRNA (TINCR) is a lncRNA which have been linked with many cancers including TNBC. The expression and behavior of TINCR may exert unfavorable outcome in TNBCs. Nevertheless, the underlying molecular mechanism of TINCR in driving chemoresistance in TNBC is not well understood. This review will highlight the potential molecular mechanisms of TINCR in TNBC chemoresistance and how it can serve as a future potential prognostic and therapeutic target for a better treatment intervention.

Antiproliferative Activities of Acetone Extract From Canarium Odontophyllum (Dabai) Stem Bark Against Human Colorectal Cancer Cells.

Colorectal cancer is the most common malignant cancer in developing countries. Canarium odontophyllum, also known as "Dabai" or "Borneo Olive" is among the natural plants that can potentially be used as an anticancer agent. This study aims to determine the antiproliferative activities and cytotoxicity effects of acetone extract from C. odontophyllum stem bark against human colorectal cancer cell lines HCT 116 and HT 29. Acetone extract of C. odontophyllum stem bark exerted a significant cytotoxic effect on HCT 116 and HT 29 cells determined by MTT assay at the concentration of 12.5 µg/mL to 200 µg/mL for 24, 48, and 72 hours treatment. It was found that acetone extract of C. odontophyllum stem bark inhibited proliferation of HCT 116 with an IC50 value of 184.93 ± .0 µg/mL, 61.24 ± .1 µg/mL, 79.98 ± .029 for 24, 48 and 72 hours respectively. The findings also showed that acetone extract of C. odontophyllum stem bark revealed a lower inhibitory effect against HT-29 with an IC50 value of more than 200 µg/mL for 24, 48 and 72 hours. However, acetone extract of C. odontophyllum stem bark at similar concentrations and time points did not show any cytotoxic effect to normal colorectal fibroblast cell CCD18-Co. In conclusion, the acetone extract of C. odontophyllum stem bark exhibited more sensitivity against HCT 116 than HT 29. Its antiproliferative ability towards HCT 116 and HT 29 cells provides insight that this extract may serve as an anticancer agent against colorectal cancer.

Genotoxicity and apoptotic effect of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine on malignant melanoma cells, SK-MEL-28.

Complexes of coinage metals can potentially be used as alternatives to platinum-based chemotherapeutic drugs. Silver is a coinage metal that can potentially improve the spectrum of efficacy in various cancers treatment, such as malignant melanoma. Melanoma is the most aggressive form of skin cancer that is often diagnosed in young and middle-aged adults. Silver has high reactivity with skin proteins and can be developed as a malignant melanoma treatment modality. Therefore, this study aims to identify the anti-proliferative and genotoxic effects of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine ligands in the human melanoma SK-MEL-28 cell line. The anti-proliferative effects of a series of silver(I) complex compounds labelled as OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were evaluated on SK-MEL-28 cells by using the Sulforhodamine B assay. Then, DNA damage analysis was performed in a time-dependent manner (30 min, 1 h and 4 h) by using alkaline comet assay to investigate the genotoxicity of OHBT and BrOHMBT at their respective IC50 values. The mode of cell death was studied using Annexin V-FITC/PI flow cytometry assay. Our current findings demonstrated that all silver(I) complex compounds showed good anti-proliferative activity. The IC50 values of OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were 2.38 ± 0.3 µM, 2.70 ± 0.17 µM, 1.34 ± 0.22 µM, 2.82 ± 0.45 µM, and 0.64 ± 0.04 µM respectively. Then, DNA damage analysis showed that OHBT and BrOHMBT could induce DNA strand breaks in a time-dependent manner, with OHBT being more prominent than BrOHMBT. This effect was accompanied by apoptosis induction in SK-MEL-28, as evaluated using Annexin V-FITC/PI assay. In conclusion, silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine exerted anti-proliferative activities by inhibiting cancer cell growth, inducing significant DNA damage and ultimately resulting in apoptosis.

Upregulation of APOC1 Promotes Colorectal Cancer Progression and Serves as a Potential Therapeutic Target Based on Bioinformatics Analysis.

Background: Approximately 10% of cancer patients worldwide have colorectal cancer (CRC), a prevalent gastrointestinal malignancy with substantial mortality and morbidity. The purpose of this work was to investigate the APOC1 gene's expression patterns in the CRC tumor microenvironment and, using the findings from bioinformatics, to assess the biological function of APOC1 in the development of CRC. Methods: The TCGA portal was employed in this investigation to find APOC1 expression in CRC. Its correlation with other genes and clinicopathological data was examined using the UALCAN database. To validate APOC1's cellular location, the Human Protein was employed. In order to forecast the relationship between APOC1 expression and prognosis in CRC patients, the Kaplan-Meier plotter database was used. TISIDB was also employed to evaluate the connection between immune responses and APOC1 expression in CRC. The interactions of APOC1 with other proteins were predicted using STRING. In order to understand the factors that contribute to liver metastasis from CRC, single-cell RNA sequencing (scRNA-seq) was done on one patient who had the disease. This procedure included sampling preoperative blood and the main colorectal cancer tissues, surrounding colorectal cancer normal tissues, liver metastatic cancer tissues, and normal liver tissues. Finally, an in vitro knockdown method was used to assess how APOC1 expression in tumor-associated macrophages (TAMs) affected CRC cancer cell growth and migration. Results: When compared to paracancerous tissues, APOC1 expression was considerably higher in CRC tissues. The clinicopathological stage and the prognosis of CRC patients had a positive correlation with APOC1 upregulation and a negative correlation, respectively. APOC1 proteins are mostly found in cell cytosols where they may interact with APOE, RAB42, and TREM2. APOC1 was also discovered to have a substantial relationship with immunoinhibitors (CD274, IDO1, and IL10) and immunostimulators (PVR, CD86, and ICOS). According to the results of scRNA-seq, we found that TAMs of CRC tissues had considerably more APOC1 than other cell groups. The proliferation and migration of CRC cells were impeded in vitro by APOC1 knockdown in TAMs. Conclusion: Based on scRNA-seq research, the current study shows that APOC1 was overexpressed in TAMs from CRC tissues. By inhibiting APOC1 in TAMs, CRC progression was reduced in vitro, offering a new tactic and giving CRC patients fresh hope.

Efficacy of zinc carnosine in the treatment of colorectal cancer and its potential in combination with immunotherapy in vivo.

BACKGROUND: A complex of Zn and carnosine, called Zinc-L-carnosine (ZnC), enjoys a wide application as part of a Zn supplement therapeutic method as well as in treating peptic ulcers. However, researches fail to confirm the biological functions possessed by ZnC as well as tumor immune microenvironment in colorectal cancer (CRC). METHODS: Cell counting kit 8(CCK8), 5-ethynyl-2'-deoxyuridine (EdU), transwell and wound healing assays were conducted to study the influence of ZnC in the proliferating, invading and migrating processes of CRC cell lines (HCT116, LOVO) in vitro. The antitumor activity ZnC as well as its effects on tumor immune microenvironment were then assessed using CRC subcutaneous tumors in the C57BL/6 mouse model. RESULTS: According to CCK8, EdU, transwell and wound healing assays, ZnC inhibited CRC cell lines in terms of proliferation, invasion and migration. ZnC could inhibit miR-570 for up-regulating PD-L1 expression. In vivo experiments showed that gavage (100 mg/kg, once every day) of ZnC inhibited the tumor growth of CRC, and the combination of ZnC and anti-PD1 therapy significantly improved the efficacy exhibited by anti-PD1 in treating CRC. In addition, mass cytometry results showed that immunosuppressive cells including regulatory T cells (tregs), bone marrow-derived suppressor cells (MDSC), and M2 macrophages decreased whereas CD8+ T cells elevated after adding ZnC. CONCLUSIONS: The present study reveals that ZnC slows the progression of CRC by inhibiting CRC cells in terms of proliferation, invasion and migration, meanwhile up-regulating PD-L1 expression via inhibiting miR-570. The ZnC-anti-PD1 co-treatment assists in synergically increasing anti-tumor efficacy in CRC therapy.

Tissue Rigidity Increased during Carcinogenesis of NTCU-Induced Lung Squamous Cell Carcinoma In Vivo.

Increased tissue rigidity is an emerging hallmark of cancer as it plays a critical role in promoting cancer growth. However, the field lacks a defined characterization of tissue rigidity in dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) in vivo. Pre-malignant and malignant lung SCC was developed in BALB/c mice using N-nitroso-tris-chloroethylurea (NTCU). Picro sirius red staining and atomic force microscopy were performed to measure collagen content and collagen (diameter and rigidity), respectively. Then, the expression of tenascin C (TNC) protein was determined using immunohistochemistry staining. Briefly, all tissue rigidity parameters were found to be increased in the Cancer group as compared with the Vehicle group. Importantly, collagen content (33.63 ± 2.39%) and TNC expression (7.97 ± 2.04%) were found to be significantly higher (p < 0.05) in the Malignant Cancer group, as compared with the collagen content (18.08 ± 1.75%) and TNC expression (0.45 ± 0.53%) in the Pre-malignant Cancer group, indicating increased tissue rigidity during carcinogenesis of lung SCC. Overall, tissue rigidity of lung SCC was suggested to be increased during carcinogenesis as indicated by the overexpression of collagen and TNC protein, which may warrant further research as novel therapeutic targets to treat lung SCC effectively.

Rigid Tissue Increases Cytoplasmic pYAP Expression in Pre-Malignant Stage of Lung Squamous Cell Carcinoma (SCC) In Vivo.

Increased tissue rigidity is able to activate the Hippo signaling pathway, leading to YAP inactivation by phosphorylation and translocation into the cytoplasm. Accumulating evidence suggests that cytoplasmic pYAP serves as a tumor suppressor and could be a prognostic biomarker for several solid cancers. However, the relationship between tissue rigidity and cytoplasmic pYAP expression in the early stage of lung squamous cell carcinoma (SCC) remains elusive; this was determined in this study by using a mouse model. Female BALB/c mice were assigned into two groups (n = 6; the vehicle (VC) and the pre-malignant (PM) group, which received 70% acetone and 0.04 M N-nitroso-tris-chloroethylurea (NTCU) for 15 weeks, respectively. In this study, the formation of hyperplasia and metaplasia lesions was found in the PM group, indicating the pre-malignant stage of lung SCC. The pre-malignant tissue appeared to be more rigid as characterized by significantly higher (p < 0.05) epithelium thickness, proliferative activity, and collagen content than the VC group. The PM group also had a significantly higher (p < 0.05) cytoplasmic pYAP protein expression than the VC group. In conclusion, increased tissue rigidity may contribute to the upregulation of cytoplasmic pYAP expression, which may act as a tumor suppressor in the early stage of lung SCC.

Incidence and Predictors of Mortality among Community-Dwelling Older Adults in Malaysia: A 5 Years Longitudinal Study.

With older adults accounting for 10.7% of the Malaysian population, determining the predictors of mortality has now become crucial. Thus, this community-based longitudinal study aimed to investigate the predictors for mortality among community-dwelling older adults using a wide range of factors, including clinical or subclinical. A total of 2322 older adults were interviewed and assessed by trained fieldworkers using validated structured questionnaires. The questionnaire consisted of information on socio-demographic characteristics, health status, neuropsychological and psychosocial functions, lifestyle, dietary intake and biophysical measures. The incidence rate of mortality was 2.9 per 100 person-years. Cox regression analysis indicated that advancing age (Adjusted Hazard Ratio, Adj HR = 1.044, 95% CI: 1.024-1.064), male (Adj HR = 1.937, 95% CI: 1.402-2.675), non-married status (Adj HR = 1.410, 95% CI: 1.078-1.843), smoking (Adj HR = 1.314, 95% CI: 1.004-1.721), a higher fasting blood sugar (Adj HR = 1.075, 95% CI: 1.029-1.166), a lower serum albumin (Adj HR = 0.947, 95% CI: 0.905-0.990), a longer time to complete the TUG test (Adj HR = 1.059, 95% CI: 1.022-1.098), and a lower intake of total dietary fibre (Adj HR = 0.911, 95% CI: 0.873-0.980) were the predictors of mortality in this study. These findings provide an estimated rate of multiethnic mortality in middle-income countries and diet is one of the predictors. These predictors of mortality could be a reference in identifying new public health strategies to ensure longer healthier life spans with lower disability rate among community-dwelling older adults in Malaysia.

A Cell-Based Systematic Review on the Role of Annexin A1 in Triple-Negative Breast Cancers.

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype that is often associated with a poorer prognosis and does not respond to hormonal therapy. Increasing evidence highlights the exploitability of Annexin A1 (AnxA1), a calcium dependent protein, as a precision medicine for TNBC. To systematically summarize the role of AnxA1 and its associated mechanisms in TNBC, we performed data mining using three main databases: PubMed, Scopus, and Ovid/Medline. The papers retrieved were based on two different sets of key words such as "Annexin A1" or "Lipocortin 1" and "Breast cancer" or "TNBC". A total of 388 articles were identified, with 210 chosen for comprehensive screening and 13 papers that met inclusion criteria were included. Current evidence from cell culture studies showed that AnxA1 expression is correlated with NF-κB, which promotes migration by activating ERK phosphorylation. AnxaA1 also activates TGF-ß signaling which upregulates MMP-9 and miR196a expression to enhance epithelial-mesenchymal transition and migratory capacity of TNBC cells. AnxA1 can steer the macrophage polarization toward the M2 phenotype to create a pro-tumor immune environment. Existing research suggests a potential role of AnxA1 in the metastasis and immune landscape of TNBC tumors. Preclinical and clinical experiments are warranted to investigate the feasibility and effectiveness of targeting AnxA1 in TNBC.

Curcumin piperidone derivatives induce anti-proliferative and anti-migratory effects in LN-18 human glioblastoma cells.

Curcumin has demonstrated potential cytotoxicity across various cell lines despite its poor bioavailability and rapid metabolism. Therefore, our group have synthesized curcuminoid analogues with piperidone derivatives, FLDP-5 and FLDP-8 to overcome these limitations. In this study, the analogues were assessed on LN-18 human glioblastoma cells in comparison to curcumin. Results from cytotoxicity assessment showed that FLDP-5 and FLDP-8 curcuminoid analogues caused death in LN-18 cells in a concentration-dependent manner after 24-h treatment with much lower IC50 values of 2.5 µM and 4 µM respectively, which were more potent compared to curcumin with IC50 of 31 µM. Moreover, a significant increase (p < 0.05) in the level of superoxide anion and hydrogen peroxide upon 2-h and 6-h treatment confirmed the oxidative stress involvement in the cell death process induced by these analogues. These analogues also showed potent anti-migratory effects through inhibition of LN-18 cells' migration and invasion. In addition, cell cycle analysis showed that these analogues are capable of inducing significant (p < 0.05) S-phase cell cycle arrest during the 24-h treatment as compared to untreated, which explained the reduced proliferation indicated by MTT assay. In conclusion, these curcuminoid analogues exhibit potent anti-cancer effects with anti-proliferative and anti-migratory properties towards LN-18 cells as compared to curcumin.

Zinc carnosine: Frontiers advances of supplement for cancer therapy.

Zinc (Zn) has an existence within large quantities in the human brain, while accumulating within synaptic vesicle. There is growing evidence that Zn metabolic equilibrium breaking participates into different diseases (e.g., vascular dementia, carcinoma, Alzheimer's disease). Carnosine refers to an endogenic dipeptide abundant in skeletal muscle and brains and exerts a variety of positive influences (e.g., carcinoma resistance, crosslinking resistance, metal chelation and oxidation limitation). A complex of Zn and carnosine, called Zinc-L-carnosine (ZnC), has been extensively employed within Zn supplement therapeutic method and the treating approach for ulcers. ZnC has been shown to play a variety of roles in the body, including inhibiting intracellular reactive oxygen species(ROS) and free radical levels, inhibiting inflammation, supplementing zinc enzymes and promoting wound healing and mucosal cell repair. The present study conducting a reviewing process for the advances of ZnC in tumor adjuvant therapy.

The effects of polyphenols-rich tropical fruit juice on cognitive function and metabolomics profile - a randomized controlled trial in middle-aged women.

Objectives: Polyphenols, particularly anthocyanins, have received attention in improving health issues during old age, including decline in cognitive function and other health parameters. We aimed to determine the effects of polyphenols-rich tropical fruit TP 3-in-1™ juice towards improving cognitive function, oxidative stress and metabolomics profiles among middle-aged women.Methods: This clinical trial involved 31 subjects with signs of poor cognitive function, as assessed using the Rey Auditory Verbal Learning Test (RAVLT). They were randomized to receive either TP 3-in-1™ juice (n = 16) or placebo (n = 15). Study subjects consumed 500 ml of beverages for three times per day, three days per week, for a period of ten weeks. Juice supplementation provided 9135 mg GAE of total phenolic content and 194.1 mg cyanidin-3-glucoside of total anthocyanin monomer.Results: There was a significant interaction effects on RAVLT immediate recall (p < 0.05) and Comprehensive Trail Making Test (CTMT) Trail 4 (p < 0.05). Metabolomics analysis showed the presence of metabolites related to polyphenols intake and cognitive functions with the intervention group showed increased urinary excretion of thyroxine and 3-methyladenine. Thyroxine and 3-methyladenine give stability to human transthyretin (TTR) and activate autophagy, respectively, which are associated with the pathogenesis of Alzheimer's disease.Conclusion: The result shows the potential of TP 3-in-1™ juice which is rich in anthocyanins in improving cognitive function, particularly learning, memory, processing speed, sequencing, mental flexibility and visual-motor skills domains, among middle-aged women.

Dietary Pattern, Genomic Stability and Relative Cancer Risk in Asian Food Landscape.

The incidence of cancer globally is increasing, partly due to lifestyle factors. Despite a better understanding of cancer biology and advancement in cancer management and therapies, current strategies in cancer treatment remain costly and cause socioeconomic burden especially in Asian countries. Hence, instead of putting more efforts in searches for new cancer cures, attention has now shifted to understanding how to mitigate cancer risk by modulating lifestyle factors. It has been established that carcinogenesis is multifactorial, and the important detrimental role of oxidative stress, chronic inflammation, and genomic instability is evident. To date, there is no study linking dietary pattern and genomic stability in cancer risk in the Asian food landscape. Thus, this present review article discusses recent literature on dietary pattern and genomic stability and its relationship with cancer risk in Asia.

NTCU induced pre-malignant and malignant stages of lung squamous cell carcinoma in mice model.

Mice have served as an excellent model to understand the etiology of lung cancer for years. However, data regarding dual-stage carcinogenesis of lung squamous cell carcinoma (SCC) remain elusive. Therefore, we aim to develop pre-malignant (PM) and malignant (M) lung SCC in vivo using N-nitroso-tris-chloroethylurea (NTCU). BALB/C mice were allotted into two main groups; PM and M groups which received treatment for 15 and 30 weeks, respectively. Then, the mice in each main group were allotted into three groups; control, vehicle, and cancer (n = 6), which received normal saline, 70% acetone, and 0.04 M NTCU by skin painting, respectively. Histopathologically, we discovered a mix of hyperplasia, metaplasia, and dysplasia lesions in the PM group and intracellular bridge; an SCC feature in the M group. The M group was positive for cytokeratin 5/6 protein which confirmed the lung SCC subtype. We also found significantly higher (P < 0.05) epithelium thickness in the cancer groups as compared to the vehicle and control groups at both the PM and M. Overall, this study discovered that NTCU is capable of developing PM and M lung SCC in mice model at appropriate weeks and the vehicle group was suggested to be adequate as control group for future research.

Combination Therapy of Navitoclax with Chemotherapeutic Agents in Solid Tumors and Blood Cancer: A Review of Current Evidence.

Combination therapy emerges as a fundamental scheme in cancer. Many targeted therapeutic agents are developed to be used with chemotherapy or radiation therapy to enhance drug efficacy and reduce toxicity effects. ABT-263, known as navitoclax, mimics the BH3-only proteins of the BCL-2 family and has a high affinity towards pro-survival BCL-2 family proteins (i.e., BCL-XL, BCL-2, BCL-W) to induce cell apoptosis effectively. A single navitoclax action potently ameliorates several tumor progressions, including blood and bone marrow cancer, as well as small cell lung carcinoma. Not only that, but navitoclax alone also therapeutically affects fibrotic disease. Nevertheless, outcomes from the clinical trial of a single navitoclax agent in patients with advanced and relapsed small cell lung cancer demonstrated a limited anti-cancer activity. This brings accumulating evidence of navitoclax to be used concomitantly with other chemotherapeutic agents in several solid and non-solid tumors that are therapeutically benefiting from navitoclax treatment in preclinical studies. Initially, we justify the anti-cancer role of navitoclax in combination therapy. Then, we evaluate the current evidence of navitoclax in combination with the chemotherapeutic agents comprehensively to indicate the primary regulator of this combination strategy in order to produce a therapeutic effect.

Immunomodulatory potential of Clinacanthus nutans extracts in the co-culture of triple-negative breast cancer cells, MDA-MB-231, and THP-1 macrophages.

Triple-negative breast cancer is the main type of breast carcinoma that causes mortality among women because of the limited treatment options and high recurrence. Chronic inflammation has been linked with the tumor microenvironment (TME) in breast cancer progression. Clinacanthus nutans (CN) has gained much attention because of its anticancer properties, but its mechanism remains unclear. We aimed to study the qualitative phytochemical content and elucidate the cytotoxicity effects of CN on human triple-negative breast cancer (TNBC), MDA-MB-231 and human macrophage-like cells such as THP-1 by using sulforhodamine B (SRB) assay. As highly metastatic cells, MDA-MB-231 cells can migrate to the distal position, the effect of CN on migration were also elucidated using the scratch assay. The CN effects on ameliorating chronic inflammation in TME were studied following the co-culture of MDA-MB-231/THP-1 macrophages. The cytokine expression levels of IL-6, IL-1ß and tumor necrosis factor-alpha (TNF-α) were determined using ELISA assays. The results showed that both ethanolic and aqueous CN extracts contained alkaloid, phenol and tannin, flavonoid, terpenoid, glycoside and steroid. However, saponin was only found in the aqueous extract of CN. CN was not cytotoxic to both MDA-MB-231 and THP-1 cells. The ability of MDA-MB-231 to migrate was also not halted by CN treatment. However, CN ethanol extract decreased IL-6 at 25 µg/mL (p = 0.02) and 100 µg/mL (p = 0.03) but CN aqueous extract increased IL-6 expression at 50 µg/mL (p = 0.08) and 100 µg/mL (p = 0.02). IL-1ß showed decreased expression after treated with CN ethanol and CN aqueous both at 25 µg/mL (p = 0.03). TNF-α were significantly decreased after CN ethanol treatment at concentration 25- (p = 0.001), 50- (p = 0.000) and 100 µg/mL (p = 0.000). CN aqueous extract slightly inhibited TNF-α at all 25-50- and 100 µg/mL (p = 0.001, p = 0.000, p = 0.000, respectively). Overall, CN acts by ameliorating the pro-inflammatory condition in the TME and may be a potential strategy for its anticancer mechanism on highly metastatic breast cancer condition. The major pathways that link both cancer and inflammation were NF-κB and STATs thus further study on the upstream and downstream pathways is needed to fully understand the mechanism of CN extracts in cooling the inflamed TME in breast cancer.