Cinnamaldehyde-Rich Cinnamon Extract Induces Cell Death in Colon Cancer Cell Lines HCT 116 and HT-29.

Cinnamon is a natural spice with a wide range of pharmacological functions, including anti-microbial, antioxidant, and anti-tumor activities. The aim of this study is to investigate the effects of cinnamaldehyde-rich cinnamon extract (CRCE) on the colorectal cancer cell lines HCT 116 and HT-29. The gas chromatography mass spectrometry analysis of a lipophilic extract of cinnamon revealed the dominance of trans-cinnamaldehyde. Cells treated with CRCE (10-60 µg/mL) showed significantly decreased cell viability in a time- and dose-dependent manner. We also observed that cell proliferation and migration capacity were inhibited in CRCE-treated cells. In addition, a remarkable increase in the number of sub-G1-phase cells was observed with arrest at the G2 phase by CRCE treatment. CRCE also induced mitochondrial stress, and finally, CRCE treatment resulted in activation of apoptotic proteins Caspase-3, -9, and PARP and decreased levels of mu-2-related death-inducing gene protein expression with BH3-interacting domain death agonist (BID) activation.

Nano-priming as emerging seed priming technology for sustainable agriculture-recent developments and future perspectives.

Nano-priming is an innovative seed priming technology that helps to improve seed germination, seed growth, and yield by providing resistance to various stresses in plants. Nano-priming is a considerably more effective method compared to all other seed priming methods. The salient features of nanoparticles (NPs) in seed priming are to develop electron exchange and enhanced surface reaction capabilities associated with various components of plant cells and tissues. Nano-priming induces the formation of nanopores in shoot and helps in the uptake of water absorption, activates reactive oxygen species (ROS)/antioxidant mechanisms in seeds, and forms hydroxyl radicals to loosen the walls of the cells and acts as an inducer for rapid hydrolysis of starch. It also induces the expression of aquaporin genes that are involved in the intake of water and also mediates H2O2, or ROS, dispersed over biological membranes. Nano-priming induces starch degradation via the stimulation of amylase, which results in the stimulation of seed germination. Nano-priming induces a mild ROS that acts as a primary signaling cue for various signaling cascade events that participate in secondary metabolite production and stress tolerance. This review provides details on the possible mechanisms by which nano-priming induces breaking seed dormancy, promotion of seed germination, and their impact on primary and secondary metabolite production. In addition, the use of nano-based fertilizer and pesticides as effective materials in nano-priming and plant growth development were also discussed, considering their recent status and future perspectives.

Astaxanthin Sensitizes Low SOD2-Expressing GBM Cell Lines to TRAIL Treatment via Pathway Involving Mitochondrial Membrane Depolarization.

Carotenoids have been suggested to have either anti- or pro-oxidative effects in several cancer cells, and those effects can trigger an unbalanced reactive oxygen species (ROS) production resulting in an apoptotic response. Our study aimed to evaluate the effect of the well-known carotenoid 3, 3'-dihydroxy-ß, ß'-carotene-4, 4-dione (astaxanthin, AXT) on glioblastoma multiforme (GBM) cells, especially as a pretreatment of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), that was previously shown to increase ROS and to induce apoptosis in cancer cells. We found that AXT by itself did not trigger apoptosis in four investigated GBM cell lines upon a 24 h treatment at various concentrations from 2.5 to 50 µM. However, in U251-MG and T98-MG GBM cells, pretreatment of 2.5 to 10 µM AXT sensitized cells to TRAIL treatment in a statistically significant manner (p < 0.05) while it did not affect CRT-MG and U87-MG GBM cells. We further compared AXT-sensitive U251-MG and -insensitive CRT-MG response to AXT and showed that 5 µM AXT treatment had a beneficial effect on both cell lines, as it enhanced mitochondrial potential and TRAIL treatment had the opposite effect, as it decreased mitochondrial potential. Interestingly, in U251-MG, 5 µM AXT pretreatment to TRAIL-treated cells mitochondrial potential further decreased compared to TRAIL alone cells. In addition, while 25 and 50 ng/mL TRAIL treatment increased ROS for both cell lines, pretreatment of 5 µM AXT induced a significant ROS decrease in CRT-MG (p < 0.05) while less effective in U251-MG. We found that in U251-MG, superoxide dismutase (SOD) 2 expression and enzymatic activity were lower compared to CRT-MG and that overexpression of SOD2 in U251-MG abolished AXT sensitization to TRAIL treatment. Taken together, these results suggest that while AXT acts as an ROS scavenger in GBM cell lines, it also has some role in decreasing mitochondrial potential together with TRAIL in a pathway that can be inhibited by SOD2.

Soybean Processing Wastes: Novel Insights on Their Production, Extraction of Isoflavones, and Their Therapeutic Properties.

Soybean processing waste (SPW) has potential as a sustainable source of phytochemicals and functional foods. A variety of phytochemicals, nutrients, and minerals have been characterized from SPW using various analytical methods. SPW utilization strategies may provide a new way to increase production of bioactive compounds, nutritional supplements, and cosmetic ingredients. SPW has the potential for value-added processing, to improve commercial use, and to lower environmental pollution through proper use. Okara, a byproduct generated during soybean processing of tofu and soy milk, is rich in dietary fiber, isoflavones, and saponins. Isoflavones, an important class of biologically active compounds owing to their multifunctional and therapeutic effects, are extracted from SPW. Further, studies have shown that okara has potential prebiotic and therapeutic value in lowering the risk of noncommunicable diseases. Therefore, in this review, we focus on several extraction methods and pharmacotherapeutic effects of different SPWs. Their effective uses in functional foods, nutraceuticals, and health applications, as biocatalysts, and as value-added resources have been discussed.

Quercetin-3-Glucoside Extracted from Apple Pomace Induces Cell Cycle Arrest and Apoptosis by Increasing Intracellular ROS Levels.

Cervical cancer is a life-threatening disease and the fourth most common cancer among women worldwide. Apple pomace is a multifunctional phenolic compound possessing effective biological activity against cervical cancer cells. This study aimed to investigate the anticancer effects of quercetin-3-glucoside (Q3G) extracted from apple pomace in HeLa cell lines and analyze its molecular mechanisms. High-performance liquid chromatography revealed that Q3G, coumaric acid, phloridzin, quercetin, and phloretin are the major polyphenolic compounds constituting apple pomace. Among them, Q3G possessed the greatest antioxidant and anti-inflammatory effects in vitro and exhibited significant cytotoxic effects in HeLa cells in a dose-and time-dependent manner. Flow cytometric analysis indicated that Q3G induced cell cycle arrest at the S phase in a time-dependent manner by altering cyclin-dependent kinase 2. Moreover, it induced apoptosis via chromosomal DNA degradation and increased reactive oxygen species generation. Furthermore, Q3G treatment altered the apoptosis-associated protein expression in the cells by activating caspase-9/-3, downregulating anti-apoptosis protein B-cell lymphoma (Bcl)-2 expressions and up regulating the pro-apoptotic Bcl-2-associated X protein. BH3-interacting domain death agonist cleavage occurred prior to the degradation of an anti-apoptotic Mu-2-related death-inducing gene involved in cell death signaling. Consequently, apple pomace Q3G holds promise as an anti-inflammatory and anticancer agent for treating cervical cancer.

Role of adaptin protein complexes in intracellular trafficking and their impact on diseases.

Adaptin proteins (APs) play a crucial role in intracellular cell trafficking. The 'classical' role of APs is carried out by AP1‒3, which bind to clathrin, cargo, and accessory proteins. Accordingly, AP1-3 are crucial for both vesicle formation and sorting. All APs consist of four subunits that are indispensable for their functions. In fact, based on studies using cells, model organism knockdown/knock-out, and human variants, each subunit plays crucial roles and contributes to the specificity of each AP. These studies also revealed that the sorting and intracellular trafficking function of AP can exert varying effects on pathology by controlling features such as cell development, signal transduction related to the apoptosis and proliferation pathways in cancer cells, organelle integrity, receptor presentation, and viral infection. Although the roles and functions of AP1‒3 are relatively well studied, the functions of the less abundant and more recently identified APs, AP4 and AP5, are still to be investigated. Further studies on these APs may enable a better understanding and targeting of specific diseases.APs known or suggested locations and functions.

Comparative analysis of metabolic variations, antioxidant potential and cytotoxic effects in different parts of Chelidonium majus L.

Metabolic variations, antioxidant potential and cytotoxic effects were investigated in the different plant parts like the leaf, stem, flower, pod, and root of C. majus L. using spectroscopic and chromatographic methods. Total phenolics and flavonoids were studied in the different parts of C. majus L., leaf showed higher flavonoid content (137.43 mg/g), while the pod showed the highest phenolic (23.67 mg/g) content, when compared with the stem, flower and root. In the ABTS antioxidant assay, the flower extract showed 57.94% effect, while the leaf, pod and root extract exhibited 39.10%, 36.08% and 28.88% activity, respectively. The pod and leaf extracts demonstrated the potential effect, exhibiting 45.46 and 41.61% activity, respectively, for the DPPH assay. Similar to the phosphomolybdenum assay, the flower revealed higher antioxidant activity (46.82%) than the other plant parts. The in vitro SRB assay facilitated evaluation of the cytotoxic effect against the HeLa and CaSki human cervical cancerous cells. The extract displayed dose-dependent inhibitory effect on both the cell lines. The highest cytotoxic effect was observed in the pod and flower extracts post 48 h of exposure at 1000 µg/mL. The results of C. majus L. offered new insights in the preliminary steps regarding the development of a high value product for phytomedicine applications though promising metabolic variations with antioxidant and anticancer potentials.

Spiraeoside extracted from red onion skin ameliorates apoptosis and exerts potent antitumor, antioxidant and enzyme inhibitory effects.

Red onion skin waste (ROSW) was analyzed for extraction of naturally occurring 4'-O-glucoside of quercetin, spiraeoside (SPI) with promising biological activities. Reversed-phase high-performance liquid chromatography was used to determine the SPI content in three different solvent extracts of ROSW: water (12.2 mg/g), methanol (27.6 mg/g), and ethanol (32.5 mg/g). The ethanol extract and SPI showed significant radical-scavenging and anti-inflammatory activities. In addition, the anti-cancer effects of SPI on a HeLa cells was investigated. The results indicated that SPI treatment significantly inhibited cell growth, and the dose of 50 µg/mL exhibited the highest anti-cancer activity. SPI inhibited the expression of B-cell lymphoma 2 and BH3-interacting domain-death agonist and promoted apoptosis by activating caspase-9/-3 expression. Notably, SPI inhibited the expression of mu-2-related death-inducing gene, a molecule involved in death receptor-mediated apoptotic signaling. Cyclin-dependent kinase 2-cyclin-E expression was also inhibited after SPI treatment, particularly at the G2/M checkpoint. Our findings provide novel insights into the apoptotic potential with promising anticancer and enzyme inhibitory effects of ROSW SPI.

Recent advances in potential drug therapies combating COVID-19 and related coronaviruses-A perspective.

Coronaviruses (CoVs) are a large family of viruses responsible for the severe pathophysiological effects on human health. The most severe outbreak includes Severe Acute Respiratory Syndrome (SARS-CoV), Middle East Respiratory Syndrome (MERS-CoV) and Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2). The COVID-19 poses major challenges to clinical management because no specific FDA-approved therapy yet to be available. Thus, the existing therapies are being used for the treatment of COVID-19, which are under clinical trials and compassionate use, based on in vitro and in silico studies. In this review, we summarize the potential therapies utilizing small molecules, bioactive compounds, nucleoside and nucleotide analogs, peptides, antibodies, natural products, and synthetic compounds targeting the complex molecular signaling network involved in COVID-19. In this review＞230 natural and chemically synthesized drug therapies are described with their recent advances in research and development being done in terms of their chemical, structural and functional properties. This review focuses on possible targets for viral cells, viral proteins, viral replication, and different molecular pathways for the discovery of novel viral- and host-based therapeutic targets against SARS-CoV-2.

Novel insights on the multi-functional properties of flavonol glucosides from red onion (Allium cepa L) solid waste - In vitro and in silico approach.

Flavonol glucosides was extracted from red onion solid waste (ROSW) and multi-functional properties were determined to develop alternative strategy for therapeutic beneficiation and utilisation as functional food. The major flavonol glucosides extracted from ROSW were confirmed as quercetin-3, 4'-O-diglucoside (QDG), quercetin-3-O-glucoside (isoquercetin), quercetin-4'-O-glucoside (spiraeoside), isorhamnetin- 4'-glucoside (IMG), quercetin glycoside (QG), and quercetin (Q) using a combination of chromatographic, spectroscopic and scientific literature data. The ROSW solvent fractions and extracted flavonol glucosides showed significant antioxidant effect with DPPH, ABTS, FRAP, and ORAC radical scavenging assays. The in vitro and in silico study revealed that the QG, QDG, isoquercetin, and spiraeoside from ROSW exhibited potent α-glucosidase, tyrosinase and xanthine oxidase enzyme inhibitory activity. In addition, QG, QDG, isoquercetin, and spiraeoside showed potent anticancer effect on HeLa cancer lines. Considering these results, the utilization of ROSW and their flavonol glucosides might be helpful for developing potential antioxidant, anticancer and enzyme inhibitory agents.

New insights into antiviral and cytotoxic potential of quercetin and its derivatives - A biochemical perspective.

Quercetin, a potential polyphenolic which possesses several biological effects. The influenza virus polymerase basic 2 (PB2) subunit of RNA polymerase responsible for replication, degree of virus conservation and active target site for designing specific antivirals. The quercetin derivatives downloaded from PubChem were screened using PyRX software configured with Vina Wizard, targeted on cap-binding site of the PB2 of influenza viral RNA polymerase. Among the PubChem library (total 97,585,747 compounds), 410 quercetin derivatives were screened using molecular docking (affinity: <-9.0 kcal) for their drug-likeness and in vitro cytopathic effect by Sulforhodamine B (SRB) assay. Among all quercetin derivatives, quercetin 3'-glucuronide (Q3G) showed strongest binding affinity towards cap-binding site of the PB2 subunit with -9.6 kcal of binding affinity and 0.00054 mM of Ki value, while quercetin 3'-glucuronide (Q7G) was presented highest anti-influenza activity with 2.10 ± 0.05 of IC50 on influenza A/PR/8/34 virus and non-cytotoxic effect as CC50 > 100 µg/mL.

The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?

Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.

COVID-19: Pathogenesis, cytokine storm and therapeutic potential of interferons.

The outbreak of the novel SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) responsible for coronavirus disease 2019 (COVID-19) has developed into an unprecedented global pandemic. Clinical investigations in patients with COVID-19 has shown a strong upregulation of cytokine and interferon production in SARS-CoV2- induced pneumonia, with an associated cytokine storm syndrome. Thus, the identification of existing approved therapies with proven safety profiles to treat hyperinflammation is a critical unmet need in order to reduce COVI-19 associated mortality. To date, no specific therapeutic drugs or vaccines are available to treat COVID-19 patients. This review evaluates several options that have been proposed to control SARS-CoV2 hyperinflammation and cytokine storm, eincluding antiviral drugs, vaccines, small-molecules, monoclonal antibodies, oligonucleotides, peptides, and interferons (IFNs).

Nanotechnologies in Food Science: Applications, Recent Trends, and Future Perspectives.

Nanotechnology is a key advanced technology enabling contribution, development, and sustainable impact on food, medicine, and agriculture sectors. Nanomaterials have potential to lead qualitative and quantitative production of healthier, safer, and high-quality functional foods which are perishable or semi-perishable in nature. Nanotechnologies are superior than conventional food processing technologies with increased shelf life of food products, preventing contamination, and production of enhanced food quality. This comprehensive review on nanotechnologies for functional food development describes the current trends and future perspectives of advanced nanomaterials in food sector considering processing, packaging, security, and storage. Applications of nanotechnologies enhance the food bioavailability, taste, texture, and consistency, achieved through modification of particle size, possible cluster formation, and surface charge of food nanomaterials. In addition, the nanodelivery-mediated nutraceuticals, synergistic action of nanomaterials in food protection, and the application of nanosensors in smart food packaging for monitoring the quality of the stored foods and the common methods employed for assessing the impact of nanomaterials in biological systems are also discussed.

Probing the effect of quercetin 3-glucoside from Dianthus superbus L against influenza virus infection- In vitro and in silico biochemical and toxicological screening.

Investigation of antiviral and cytotoxic effect of quercetin 3-glucoside (Q3G) from Dianthus superbus L over influenza virus infection and replication were studied. Moreover, anti-influenza mechanism was screened by time-dependent antiviral assay, virus-induced symptoms and related gene expressions. The blockade of cap-binding domain of polymerase basic protein subunit were analysed by molecular docking study. The Q3G demonstrated potent antiviral activity showing 4.93, 6.43, 9.94, 8.3, and 7.1 µg/mL of IC50 for A/PR/8/34, A/Victoria/3/75, A/WS/33, B/Maryland/1/59, and B/Lee/40, respectively. The cellular toxicity of Q3G and oseltamivir (control) were tested and >100 µg/mL of CC50 value considered as nontoxic. Influenza A virus infection induced a higher ROS production, however potentially reduced by Q3G treatment and significantly blocked virus infection induced acidic vesicular organelles (AVO). Moreover, Q3G has no inhibitory effect for neuraminidase activity but blocked virus replication through time dependent assay and showed more competitive binding affinity (-8.0 kcal/mal) than GTP (-7.0 kcal/mol) to block polymerase basic protein-2 subunit of influenza virus. Q3G from D. superbus showed potent antiviral activity against influenza A and B viruses with suppressive effect on virus-induced cellular ROS generation and AVO formation. Thus, this study provided a new line of research for Q3G to develop possible natural anti-influenza drug.

Subcritical water extraction of withanosides and withanolides from ashwagandha (Withania somnifera L) and their biological activities.

Subcritical water extraction (SWE) applied to analyses the bioactives from ashwagandha (W. somnifera) at varying temperature (100-200 °C) and extraction time (10-30 min). The effect of temperature and time has been investigated in terms of extraction yield (EY), total phenolic content (TPC), cytotoxicity, antioxidant, and enzyme inhibitory activities. The withanosides and withanolides responsible for various biological effects were quantified using high performance liquid chromatography (HPLC). The HPLC analysis revealed Withanoside V, Withanoside IV, 12-Deoxywithastramonolide, Withanolide A, and Withaferin A as a principle bioactive compounds in SWE, with high in concentration compared to microwave-assisted extraction (MAE), Soxhlet extraction (SE) and maceration (MC). For SWE the highest EY (65.6%; 200 °C for 30 min), TPC (82.5 mg GAE/g DE), antioxidant activity (DPPH: 80.3%, FRAP: 60.5% and ABTS: 78.9), and potent enzyme inhibitory effects were observed. The SWE and Withaferin A showed significant reduction in cell viability of cervical cancer (HeLa) cells, with IC50 values 10 mg/ml and 8.5 µM/ml, respectively but no cytotoxic effect for normal cells (MDCK). Thus, SWE can provide effective extraction for ashwagandha withanosides and withanolides compared MAE, SE and MC to conventional methods, which could be used for extraction of pharmacologically active fractions with therapeutic applications.

Exploitation of apple pomace towards extraction of triterpenic acids, antioxidant potential, cytotoxic effects, and inhibition of clinically important enzymes.

Apple pomace (AP) utilised for analysis of triterpenic acids (TTAs) using HPLC-MS/MS. The methanol, ethanol and ethyl acetate extracts showed high phenolic content with significant antioxidant activity compared to chloroform and n-hexane. AP TTAs; ursolic acid, betulinic acid and maslinic acid showed potent antioxidant and enzyme inhibitory effects. The IC50 values were 13.2-30.8 µg/mL (tyrosinase), 19.6-42.5 µg/mL (xanthine oxidase) and 16.6-38.6 µg/mL (urease) for AP extracts and 8.4-25.8 µg/mL (tyrosinase), 12.6-30.2 µg/mL (xanthine oxidase) and 10.1-28.6 µg/mL (urease) for TTAs, compared to the positive controls; kojic acid (10.4 ±â€¯0.06 µg/mL), allopurinol (9.6 ±â€¯0.04 µg/mL) and thiourea (8.9 ±â€¯0.02 µg/mL) towards respective enzymes. UA showed a competitive type of inhibition for tyrosinase, while BA showed a noncompetitive type of inhibition towards xanthine oxidase. In addition, the AP extracts and TTAs exerted significant cytotoxic effects towards the proliferation of cancer cell lines. AP methanol extract (IC50 of 38.5 ±â€¯4.1, 47.1 ±â€¯3.5, 70.6 ±â€¯2.3, and 50.5 ±â€¯3.9 µg/mL) and ursolic acid (IC50 of 6.5 ±â€¯0.7, 15.5 ±â€¯1.4, 20.8 ±â€¯1.3, and 5.6 ±â€¯0.8 µg/mL) showed prominent anticancer activity on Hela, Skov-3, Caski, and NCL cancer cell lines, respectively. Thus, this study shows that the AP & TTAs could be utilized for functional food development and as a potent antioxidant, anticancer, skin whitening, and anti-urolithic agents.

Horticultural oils: possible alternatives to chemical pesticides and insecticides.

The farmers and agrochemical industries lack science-based knowledge about sustainable utilization of pesticides and insecticides. The investigation on rising use of chemical pesticides and insecticides has remarkable issue related to environment pollution, soil fertility, and human health; as such, nowadays, many people prefer natural alternatives over synthetic chemicals. Natural products, like horticultural oils, play a significant role for sustainable and safe integrated pest management, providing natural alternatives to chemical pesticides and insecticides. For several decades, both plant- and petroleum-based spray oils have been always used to control various pests, mites, and insects. Currently, these horticultural oils are used as a part of the integrated pest management, which utilizes secure and non-chemical pesticides rather than conventional pesticides. Horticultural oil refers to a complex mixture of hydro-carbons with traces of sulfur- and nitrogen-based compounds, extracted from plants. The key components of horticultural oils include paraffin and olefin. The horticultural oils are considered suitable since they are non-toxic to both plants and animals, are applied easily, have low risk properties, cost-effective, and play significant role in pest control, but show little effects on the beneficial insects. As a result, these attributes make horticultural oils to be considered as secure and effective alternative for chemical insecticides and pesticides for both commercial and domestic agriculture.

Utilization of Dianthus superbus L and its bioactive compounds for antioxidant, anti-influenza and toxicological effects.

Dianthus superbus (DS) is a traditional medicinal herb well known for its medicinal and therapeutic potential and widely distributed in various Asian countries. The ethyl acetate (EA), butanol (Bu) and distilled water (DW) extracts of DS assessed for extraction of bioactive compounds and their biological activities. The chemical analysis was done using LC-MS/MS and antioxidant, anticancer and antiviral activities were determined. EA extracts showed strong anticancer activity with IC50 of 9.5, 13.8 and 69.9 µg/mL on SKOV, NCL-H1299 and Caski cancer cell lines, respectively. The Bu extracts exhibited strongest antiviral activity with respect to both influenza A and B viruses with IC50 values of 4.97 and 3.9 µg/mL, respectively. Also the metabolic profile for EA, Bu and DW extracts shows high variations and influence precisely the antioxidant, anticancer and antiviral properties. The quercetin 3- rutinoside and isorhamnetin 3- glucoside showed higher neuraminidase inhibition activity in dose dependent manner. Molecular docking study revealed that flavonol glycosides have higher binding activities towards influenza polymerase membrane glycoprotein. Correlation study showed that flavonol glycosides were linked to anti-influenza activity and cyclic peptides with anticancer activities. This study provides vital information for effective utilization of DS for medicinal, food and therapeutic purposes.

Chemopreventive Effect of ß-Cryptoxanthin on Human Cervical Carcinoma (HeLa) Cells Is Modulated through Oxidative Stress-Induced Apoptosis.

The present study was aimed to assess cellular and molecular events involved in the chemopreventive activities of ß-cryptoxanthin derived from mandarin oranges (Citrus unshiu Marc.) on human cervical carcinoma (HeLa) cells. In vitro experiments established that ß-cryptoxanthin significantly inhibited the proliferation of HeLa cells with the IC50 value of 4.5 and 3.7 µM after 24 and 48 h of treatments, respectively. ß-cryptoxanthin-treated HeLa cells exhibited enhanced levels of oxidative stress correlated with significant downregulation of anti-apoptotic Bcl-2, and upregulation of pro-apoptotic Bax mRNA expression. Moreover, ß-cryptoxanthin triggered nuclear condensation and disruption of the integrity of the mitochondrial membrane, upregulated caspase-3, -7, and -9 mRNA, and enhanced activation of caspase-3 proteins, resulting in nuclei DNA damage and apoptosis of HeLa cells. Remarkably, TUNEL assay carried out to detect nuclei DNA damage showed 52% TUNEL-positive cells after treatment with a physiological concentration of ß-cryptoxanthin (1.0 µM), which validates its potential as an anticancer drug of natural origin.