New Propargyloxy Derivatives of Galangin, Kaempferol and Fisetin-Synthesis, Spectroscopic Analysis and In Vitro Anticancer Activity on Head and Neck Cancer Cells.

Head and neck cancer (HNC) therapy is limited; therefore, new solutions are increasingly being sought among flavonoids, which exhibit numerous biological properties, including potential anticancer activity. However, because they are mostly insoluble in water, are unstable and have low bioavailability, they are subjected to chemical modification to obtain new derivatives with better properties. This study aimed to synthesize and analyze new propargyloxy derivatives of galangin, kaempferol and fisetin, and to evaluate their anticancer activity against selected HNC cell lines. The obtained derivatives were assessed by spectroscopic analysis; next, their anticancer activity was evaluated using a flow cytometer and real-time cell analysis. The results showed that only the fisetin derivative was suitable for further analysis, due to the lack of crystal formation of the compound. The fisetin derivative statistically significantly increases the number of cells in the G2/M phase (p < 0.05) and increases cyclin B1 levels. A statistically significant increase in the number of apoptotic cells after being exposed to the tested compound was also observed (p < 0.05). The data indicate that the obtained fisetin derivative exhibits anticancer activity by affecting the cell cycle and increasing apoptosis in selected HNC lines, which suggests its potential use as a new medicinal agent in the future.

Hybrids of 1,4-Naphthoquinone with Thymidine Derivatives: Synthesis, Anticancer Activity, and Molecular Docking Study.

One of the most essential health problems is cancer, the first or second cause of death worldwide. Head and neck cancers are hard to detect due to non-specific symptoms. The treatment often relies on a combination of radio and chemotherapy. For this reason, the research of new anticancer compounds is fundamental. The natural and synthetic compounds with 1,4-naphthoquinone scaffold is characterized by high anticancer activity. The study aimed to evaluate the synthesis and anticancer activity of hybrids 1,4-naphthoquinone with thymidine derivatives. The series of compounds allows us to check the influence of the substituent in the C3' position of the thymidine moiety on the cytotoxicity against squamous cancer cell lines (SCC-9 and SCC-25) and submandibular gland cancer (A-253). An annexin V/propidium iodide (PI) co-staining assay shows that derivatives cause the apoptotic in SCC-25 and A-253 cell lines. The molecular docking study examined the interaction between the active site of the BCL-2 protein and the hybrids.

Selected Flavonols in Breast and Gynecological Cancer: A Systematic Review.

The consumption of foods that are rich in phenolic compounds has chemopreventive effects on many cancers, including breast cancer, ovarian cancer, and endometrial cancer. A wide spectrum of their health-promoting properties such as antioxidant, anti-inflammatory, and anticancer activities, has been demonstrated. This paper analyzes the mechanisms of the anticancer action of selected common flavonols, including kemferol, myricetin, quercetin, fisetin, galangin, isorhamnetin, and morin, in preclinical studies, with particular emphasis on in vitro studies in gynecological cancers and breast cancer. In the future, these compounds may find applications in the prevention and treatment of gynecological cancers and breast cancer, but this requires further, more advanced research.

Kaempferol and Fisetin-Related Signaling Pathways Induce Apoptosis in Head and Neck Cancer Cells.

Despite the relative effectiveness of standard cancer treatment strategies, head and neck cancer (HNC) is still considered one of the leading causes of mortality and morbidity. While selected bioactive compounds of plant origin reveal a pro-apoptotic effect, kaempferol and fisetin flavonols have been reported as potential anti-cancer agents against malignant neoplasms. To date, their exact role in signaling pathways of head and neck cancer cells is largely unknown. Based on the various methods of cytotoxicity testing, we elucidated that kaempferol and fisetin inhibit proliferation, reduce the capacity of cell migration, and induce apoptosis in SCC-9, SCC-25, and A-253 HNC cells in a dose-dependent manner in vitro (p < 0.05, fisetin IC50 values of 38.85 µM, 62.34 µM, and 49.21 µM, and 45.03 µM, 49.90 µM, and 47.49 µM for kaempferol-SCC-9, SCC-25, and A-253, respectively). The obtained results showed that exposure to kaempferol and fisetin reduces Bcl-2 protein expression, simultaneously leading to the arrest in the G2/M and S phases of the cell cycle. Kaempferol and fisetin inhibit cell proliferation by interfering with the cell cycle, which is strongly associated with the induction of G2/M arrest, and induce apoptosis by activating caspase-3 and releasing cytochrome c in human HNC cells. In addition, investigating flavonols, by inhibiting anti-apoptotic proteins from the Bcl-2 family and damaging the mitochondrial transmembrane potential, increased the level of cytochrome c. While flavonols selectively induce apoptosis of head and neck cancer cells, they may support oncological therapy as promising agents. The discovery of new derivatives may be a breakthrough in the search for effective chemotherapeutic agents with less toxicity and thus fewer side effects.

Tissue Engineering Supporting Regenerative Strategies to Enhance Clinical Orthodontics and Dentofacial Orthopaedics: A Scoping, Perspective Review.

The personalized regenerative therapeutic strategies applicable in the structural and functional repair of maxillofacial/dental defects are expected to extend beyond the limits of what is currently possible in the management of dentofacial anomalies and treating malocclusions. The application of undifferentiated stem cells (SCs), including signaling molecule control and individualized tissue engineering based on targeted therapies, has been proposed to overcome therapeutic limitations and complications associated with treatments for craniofacial defects, including severe orthodontic discrepancies. This scoping, prospective review discusses comprehensively the current knowledge and prospects for improving clinical outcomes by the application of novel cell-required and cell-free regenerative strategies in biomedicine. The existing evidence, although scant, suggests that patients receiving an orthodontic treatment could benefit from precise tissue augmentation, allowing enhancement of tooth movement generated by orthognathic forces; faster, more predictable alignment of dental arches; optimal management of periodontal complications; and prevention of external root resorption. Ultimately, enriching orofacial tissues and "customizing" the repair of congenital/acquired defects in the craniofacial region can be vastly enhanced to provide a positive therapeutic outcome and improve patients' quality of life.

Evaluation of the biocompability and corrosion activity of resorbable CaMgZnYbBAu alloys.

Calcium-based alloys can be promising candidates for use as biodegradable implants because of attractive properties as mechanical, corrosive, and biocompatible. In the work, the biocompatibility authors discussed the results of the Ca32Mg12Zn38Yb18-xBx (x = 0, 1, 2, 3 at.%) and Ca32Mg12Zn38Yb18-2xBxAux (x = 1, 2 at.%) alloys. The tests were performed using a MTT assay. The corrosion behavior of such Ca-based alloys in PWE fluid at 37 °C was studied and compared with the results in Ringer's solution from previous works. Electrochemical tests were presented by open circuit potential and potentiodynamic curves. Different concentrations of boron and gold in the alloys caused changes in the corrosion results. The best corrosion resistance in PWE solution was observed for the Ca-based alloy with 2 at.% Au due to the lowest value of the corrosion current density (jcorr), equal to 10.6 µA·cm-2. A slightly higher value of jcorr was obtained for the Ca32Mg12Zn38Yb15B3 alloy with the lowest roughness values. The results of the cytotoxicity tests also showed that the alloy with 3 at.% boron was characterized by the highest cell viability. The investigation results discussed in the work allow us to suggest that the presented calcium alloys with 3 at.% of B, and 2 at.% of Au addition may be promising materials for the use in implantology.

COVID-19 vaccine booster hesitancy (VBH) of healthcare professionals and students in Poland: Cross-sectional survey-based study.

Since healthcare professionals (HCPs) play a critical role in shaping their local communities' attitudes toward vaccines, HCPs' beliefs and attitudes toward vaccination are of vital importance for primary prevention strategies. The present study was designed as a cross-sectional survey-based study utilizing a self-administered questionnaire to collect data about COVID-19 vaccine booster hesitancy (VBH) among Polish HCPs and students of medical universities (MUSs). Out of the 443 included participants, 76.3% were females, 52.6% were HCPs, 31.8% were previously infected by SARS-CoV-2, and 69.3% had already received COVID-19 vaccine booster doses (VBD). Overall, 74.5% of the participants were willing to receive COVID-19 VBD, while 7.9 and 17.6% exhibited their hesitance and rejection, respectively. The most commonly found promoter for acceptance was protection of one's health (95.2%), followed by protection of family's health (81.8%) and protection of community's health (63.3%). Inferential statistics did not show a significant association between COVID-19 VBH and demographic variables, e.g., age and gender; however, the participants who had been previously infected by SARS-CoV-2 were significantly more inclined to reject the VBD. Protection from severe infection, community transmission, good safety profile, and favorable risk-benefit ratio were the significant determinants of the COVID-19 VBD acceptance and uptake. Fear of post-vaccination side effects was one of the key barriers for accepting COVID-19 VBD, which is consistent with the pre-existing literature. Public health campaigns need to highlight the postulated benefits of vaccines and the expected harms of skipping VBD.

Fisetin, a Potent Anticancer Flavonol Exhibiting Cytotoxic Activity against Neoplastic Malignant Cells and Cancerous Conditions: A Scoping, Comprehensive Review.

Diet plays a crucial role in homeostasis maintenance. Plants and spices containing flavonoids have been widely used in traditional medicine for thousands of years. Flavonols present in our diet may prevent cancer initiation, promotion and progression by modulating important enzymes and receptors in signal transduction pathways related to proliferation, differentiation, apoptosis, inflammation, angiogenesis, metastasis and reversal of multidrug resistance. The anticancer activity of fisetin has been widely documented in numerous in vitro and in vivo studies. This review summarizes the worldwide, evidence-based research on the activity of fisetin toward various types of cancerous conditions, while describing the chemopreventive and therapeutic effects, molecular targets and mechanisms that contribute to the observed anticancer activity of fisetin. In addition, this review synthesized the results from preclinical studies on the use of fisetin as an anticancer agent. Based on the available literature, it might be suggested that fisetin has a bioactive potential to become a complementary drug in the prevention and treatment of cancerous conditions. However, more in-depth research is required to validate current data, so that this compound or its derivatives can enter the clinical trial phase.

Anticancer Potential of Selected Flavonols: Fisetin, Kaempferol, and Quercetin on Head and Neck Cancers.

Flavonols are ones of the most common phytochemicals found in diets rich in fruit and vegetables. Research suggests that molecular functions of flavonoids may bring a number of health benefits to people, including the following: decrease inflammation, change disease activity, and alleviate resistance to antibiotics as well as chemotherapeutics. Their antiproliferative, antioxidant, anti-inflammatory, and antineoplastic activity has been proved. They may act as antioxidants, while preventing DNA damage by scavenging reactive oxygen radicals, reinforcing DNA repair, disrupting chemical damages by induction of phase II enzymes, and modifying signal transduction pathways. One of such research areas is a potential effect of flavonoids on the risk of developing cancer. The aim of our paper is to present a systematic review of antineoplastic activity of flavonols in general. Special attention was paid to selected flavonols: fisetin, kaempferol, and quercetin in preclinical and in vitro studies. Study results prove antiproliferative and proapoptotic properties of flavonols with regard to head and neck cancer. However, few study papers evaluate specific activities during various processes associated with cancer progression. Moreover, an attempt was made to collect the majority of substantive studies on bioactive potential of the selected flavonols, especially with regard to modulation of a range of signal transduction pathways that participate in cancer development.

Caffeic Acid Phenethyl Ester (CAPE) Induced Apoptosis in Serous Ovarian Cancer OV7 Cells by Deregulation of BCL2/BAX Genes.

Ovarian cancer has the worst prognosis among all gynecological cancers. Therefore, it seems reasonable to seek new drugs that may improve the effectiveness of treatment or mitigate the adverse effects of chemotherapy. Caffeic acid phenethyl ester (CAPE) has many beneficial biological properties. The aim of the study was to assess the anticancer properties of CAPE against serum ovarian carcinoma cells. The morphology of the cells was evaluated in H-E staining and in transmission electron microscopy. The cytotoxic and proapoptotic activity of CAPE was investigated by using the XTT-NR-SRB assay, qRT-PCR analysis of BAX/BCL2 expression, and by cytometric evaluation. CAPE causes constriction in OV7 cells, numerous granulomas were observed in the cytoplasm, the cell nuclei were pyknotic. Autophagosomal vacuoles could suggest the occurrence of aponecrosis. CAPE significantly decreased the lysosomal activity and the total synthesis of cellular proteins. CAPE exhibited, dose and time dependent, cytotoxic activity against OV7 serum ovarian cancer cells. In OV7 cells CAPE induced apoptosis via dysregulation of BAX/BCL2 balance, while activated proapoptotic BAX gene expression level was 10 times higher than BCL2.

Molecular and Serological Tests for COVID-19 a Comparative Review of SARS-CoV-2 Coronavirus Laboratory and Point-of-Care Diagnostics.

Validated and accurate laboratory testing for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a crucial part of the timely management of Coronavirus Disease 2019 (COVID-19) disease, supporting the clinical decision-making process for infection control at the healthcare level and detecting asymptomatic cases. This would facilitate an appropriate treatment, a prompt isolation and consequently deceleration of the pandemic. Various laboratory tests can identify the genetic material of SARS-CoV-2 that causes COVID-19 in specimens, or specific anti-viral antibodies in blood/serum. Due to the current pandemic situation, a development of point-of-care diagnostics (POCD) allows us to substantially accelerate taking clinical decisions and implement strategic planning at the national level of preventative measures. This review summarizes and compares the available POCD and those currently under development, including quantitative reverse transcription PCR (RT-qPCR), serology immunoassays (SIAs) and protein microarray method (PMM) designed for standard and rapid COVID-19 diagnosis.

Caffeic Acid Versus Caffeic Acid Phenethyl Ester in the Treatment of Breast Cancer MCF-7 Cells: Migration Rate Inhibition.

Epithelium mammary carcinoma is a cancer with a high death rate among women. One factor having a significant impact on metastasis is cell migration. The aim of this study was to compare migration rate inhibition of caffeic acid (CA) and its phenethyl ester (CAPE) on MCF-7 breast cancer cells. Microscopic evaluation was used to determine the morphology of carcinoma cells, before and after 24-hour treatment with CA and CAPE using a dose of 50 µM. The cytotoxic effect was measured by XTT-NR-SRB assay (tetrazolium hydroxide-neutral red-Sulforhodamine B) for 24-hour and 48-hour periods, using CA and CAPE, with doses of 50 and 100 µM. These doses were used to determine cell migration inhibition using a wound closure assay for 0-hour, 8-hour, 16-hour, and 24-hour periods. Both CA and CAPE treatments displayed cytotoxic activity in a dose- and time-dependent trend. CAPE displayed IC50 values more than twice as low as CA. IC50 values for the XTT assay were as follows: CA was 102.98 µM for 24 hours and 59.12 µM for 48 hours, while CAPE was 56.39 µM for 24 hours and 28.10 µM for 48 hours. For the NR assay: CA was 84.87 µM at 24 hours and 65.05 µM at 48 hours, while CAPE was 69.05 µM at 24 hours and 29.05 µM at 48 hours. For the SRB assay: At 24 hours, CA was 83.47 µM and 53.46 µM at 48 hours, while CAPE was 38.53 µM at 24 hours and 20.15 µM at 48 hours. Both polyphenols induced migration inhibition, resulting in practically halting the wound closure. CAPE produced better results than CA with the same doses and experiment times, though both CA and CAPE displayed cytotoxic activity against MCF-7 cells, as well as inhibited migration.

Flavonoids, bioactive components of propolis, exhibit cytotoxic activity and induce cell cycle arrest and apoptosis in human breast cancer cells MDA-MB-231 and MCF-7 - a comparative study.

Breast cancer is one of the most common causes of mortality in women. Flavonoids, among other compounds, are bioactive constituents of propolis. In this comparative study, we investigated the effects of flavonoids apigenin (API), genistein (GEN), hesperidin (HES), naringin (NAR) and quercetin (QUE) on the proliferation, apoptosis, and cell cycle of two different human cancer cells - MDA-MB-231, estrogen-negative, and MCF-7, estrogen-positive receptor breast carcinoma cells. Many cytotoxic reports of flavonoids were performed by MTT assay. However, it's reported that MTT is reduced in metabolically active cells and yields an insoluble purple formazan, which indicates that obtained cytotoxic results of flavonoids could be inconsistent. Cell viability was measured by NR, neutral red assay, while the percentage of apoptotic cells and cell cycle arrest were determined by flow cytometry and Muse cell cycle assay, respectively. The results showed a high dose-dependent effect in cell viability tests. IC50 values were as follows (MCF-7/MDA-MB-231, for 48 h, in µM): 9.39/50.83 for HES, 25.19/88.17 for API, 40.26/333.51 for NAR, 49.49/47.50 for GEN and 95.12/130.10 for QUE. Flavonoid-induced apoptosis was dose- and time-dependent, for both cancer cell lines, though flavonoids were more active on MCF-7 cells. The flavonoids also induced cell cycle arrest in cancer cells.

Protective Effect of Polyphenol-Rich Extract from Bee Pollen in a High-Fat Diet.

We have studied a preventive effect of polyphenol-rich bee pollen ethanol extract (EEP) against histological changes in the liver and cardiac blood vessels, abnormalities of lipid profile, and the levels of oxidized low density lipoproteins (ox-LDL), asymmetric dimethylarginine (ADMA), angiotensin-converting enzyme (ACE), and angiotensin II (ANG II) caused by a high-fat diet in C57BL6 mice. Supplementing the diet with EEP in the doses of 0.1 g/kg body mass (BM) and 1 g/kg BM resulted in a decrease of total cholesterol by 31% and 35%, respectively. It also decreased the level of low density lipoproteins by 67% and 90%, respectively. No differences in the levels of high density lipoprotein and triacylglycerols were observed. EEP reduced the level of ox-LDL by 33% and 47%, ADMA by 13% and 51%, ACE by 17% and 30%, as well as ANG II by 11% and 15% in a dose-dependent manner, which proves a protective effect of EEP in a high-fat diet. EEP reduces and/or prevents hepatic steatosis and degenerative changes caused by a high-fat diet in C57BL6 mice, which indicates its hepatoprotective effect. EEP used with standard feed does not disturb a normal concentration of the assayed parameters.

Migration Rate Inhibition of Breast Cancer Cells Treated by Caffeic Acid and Caffeic Acid Phenethyl Ester: An In Vitro Comparison Study.

One of the deadliest cancers among women is a breast cancer. Research has shown that two natural substances occurring in propolis, caffeic acid (CA) and caffeic acid phenethyl ester (CAPE), have significant anticancer effects. The purpose of our in vitro study was to compare cytotoxic activity and migration rate inhibition using CA and CAPE (doses of 50 and 100 µm) against triple-negative, MDA-MB-231 breast adenocarcinoma line cells, drawn from Caucasian women. Viability was measured by XTT-NR-SRB assay (Tetrazolium hydroxide-Neutral Red-Sulforhodamine B) for 24 h and 48 h periods. Cell migration for wound healing assay was taken for 0 h, 8 h, 16 h, and 24 h periods. CAPE displayed more than two times higher cytotoxicity against MDA-MB-231 cells. IC50 values for the XTT assay were as follows: CA for 24 h and 48 h were 150.94 µM and 108.42 µM, respectively, while CAPE was 68.82 µM for 24 h and 55.79 µM for 48 h. For the NR assay: CA was 135.85 µM at 24 h and 103.23 µM at 48 h, while CAPE was 64.04 µM at 24 h and 53.25 µM at 48 h. For the SRB assay: CA at 24 h was 139.80 µM and at 48 h 103.98 µM, while CAPE was 66.86 µM at 24 h and 47.73 µM at 48 h. Both agents suspended the migration rate; however, CAPE displayed better activity. Notably, for the 100 µM CAPE dose, motility of the tested breast carcinoma cells was halted.

Comparison of Two Components of Propolis: Caffeic Acid (CA) and Caffeic Acid Phenethyl Ester (CAPE) Induce Apoptosis and Cell Cycle Arrest of Breast Cancer Cells MDA-MB-231.

Studies show that caffeic acid (CA) and caffeic acid phenethyl ester (CAPE) are compounds with potent chemopreventive effects. Breast cancer is a common form of aggressive cancer among women worldwide. This study shows a comparison of CA and CAPE activity on triple-negative human caucasian breast adenocarcinoma line cells (MDA-MB-231). MDA-MB-231 cells were treated by CA and CAPE with doses of from 10 to 100 µM, for periods of 24 h and 48 h. Cytotoxicity MTT tests, apoptosis by Annexin V, and cell cycle with Dead Cell Assays were performed. Cytotoxic activity was greater for CAPE compared to CA (both incubation times, same dosage). IC50 values for CAPE were 27.84 µM (24 h) and 15.83 µM (48 h) and for CA > 10,000 µM (24 h) and > 1000 µM (48 h). Polyphenols induced apoptosis, while CAPE (dose dependently), induced a higher apoptotic effect. CAPE also induced cell cycle arrest in S phase (time and dose dependently), CA did it only for 50 and 100 µM. A dose dependent decline was seen for the G0/G1 phase (CAPE, 48 h), as well as elimination of phase G2/M by 100 µM of CAPE (only mild effect for CA). Comparing CA and CAPE activity on MDA-MB-231, CAPE clearly showed better activity for the same dosages and experiment times.

Rutin, a Quercetin Glycoside, Restores Chemosensitivity in Human Breast Cancer Cells.

Several studies have documented the ability of flavonoids to sensitize cancer cells to chemotherapeutics and reverse multidrug resistance by inhibition of efflux pumps (adenosine triphosphate-binding cassette transporters), apoptosis activation, and cell cycle arrest. In this study, the flavonoid rutin (quercetin 3-O-ß-d-rutinoside) was investigated as chemosensitizer towards two different human epithelial breast cancer cell lines: (i) MB-MDA-231, selected as representative for triple-negative breast cancer and (ii) MCF-7 used as a well-characterized model of HER2-negative breast cancer. To assess the cytocompatibility of rutin against non-cancer cells, primary human mammary fibroblasts were used as control and non-target cells. In MDA-MB-231 cells, 20 µM rutin enhanced cytotoxicity related to cyclophosphamide and methotrexate. Rutin significantly (p < 0.05) increased the anticancer activity of both chemotherapeutics, at 24-48-72 h, and decreased the activity of the adenosine triphosphate-binding cassette transporters, namely, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Flow cytometry analysis showed 20 µM and 50 µM rutin arrested cell cycle at G2/M and G0/G1 phases, respectively, significantly promoting cell apoptosis. Rutin, via non-selective inhibition of P-gp and BCRP pumps, efficiently reverses multidrug resistance and restores chemosensitivity to cyclophosphamide and cyclophosphamide of human chemoresistant, triple-negative breast cancer cells, successfully arresting cell cycle progression. Copyright © 2017 John Wiley & Sons, Ltd.

Induction of Cell Cycle Arrest and Apoptotic Response of Head and Neck Squamous Carcinoma Cells (Detroit 562) by Caffeic Acid and Caffeic Acid Phenethyl Ester Derivative.

Natural polyphenols have been observed to possess antiproliferative properties. The effects, including apoptotic potential of bioactive phenolic compounds, caffeic acid (CA) and its derivative caffeic acid phenethyl ester (CAPE), on cell proliferation and apoptosis in human head and neck squamous carcinoma cells (HNSCC) line (Detroit 562) were investigated and compared. Cancer cells apoptosis rates and cell cycle arrests were analysed by flow cytometry. Exposure to CA and CAPE was found to result in a dose-dependent decrease in the viability of Detroit 562 cells at different levels. CA/CAPE treatment did significantly affect the viability of Detroit 562 cells (MTT results). CAPE-mediated loss of viability occurred at lower doses and was more pronounced, with the concentrations which inhibit the growth of cells by 50% estimated at 201.43 µM (CA) and 83.25 µM (CAPE). Dead Cell Assay with Annexin V labelling demonstrated that CA and CAPE treatment of Detroit 562 cells resulted in an induction of apoptosis at 50 µM and 100 µM doses. The rise of mainly late apoptosis was observed for 100 µM dose and CA/CAPE treatment did affect the distribution of cells in G0/G1 phase. A combination of different phenolic compounds, potentially with chemotherapeutics, could be considered as an anticancer drug.

Silver Nanoparticles Exhibit the Dose-Dependent Anti-Proliferative Effect against Human Squamous Carcinoma Cells Attenuated in the Presence of Berberine.

The biological activity of nanosize silver particles towards oral epithelium-derived carcinoma seems to be still underinvestigated. We evaluated the influence of low doses of nanosize scale silver particles on the proliferation and viability of malignant oral epithelial keratinocytes in vitro, alone and in conjunction with the plant alkaloid berberine. Cells of human tongue squamous carcinoma SCC-25 (ATCC CRL-1628), cultivated with the mixture of Dulbecco's modified Eagle's medium, were exposed to silver nanoparticles alone (AgNPs, concentrations from 0.31 to 10 µg/mL) and to a combination of AgNPs with berberine chloride (BER, 1/2 IC50 concentration) during 24 h and 48 h. The cytotoxic activity of AgNPs with diameters of 10 nm ± 4 nm was measured by 3-(4,5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Cell cycle analysis was performed by treating cells with propidium iodide followed by flow-activated cell sorting. RT-QPCR reaction was used to assess expression of anti-apoptotic proteins Bcl-2 and pro-apoptotic protein Bcl-2-associated X protein Bax genes expression. Monodisperse silver nanoparticles at a concentration of 10 µg/mL arrested SCC-25 cells cycle after 48 h at the G0/G1 phase in a dose- and time-dependent manner through disruption G0/G1 checkpoint, with increase of Bax/Bcl-2 ratio gene expression. AgNPs exhibit cytotoxic effects on SCC-25 malignant oral epithelial keratinocytes, which is diminished when combined with BER. The AgNPs concentration required to inhibit the growth of carcinoma cells by 50% (IC50) after 48 h was estimated at 5.19 µg/mL. AgNPs combined with BER increased the expression of Bcl-2 while decreasing the ratio of Bax/Bcl-2 in SCC-25 cells. Silver particles at low doses therefore reduce the proliferation and viability of oral squamous cell carcinoma cells. SCC-25 cells are susceptible to damage from AgNPs-induced stress, which can be regulated by the natural alkaloid berberine, suggesting that nanoparticles may be potentially used in a chemoprevention/chemotherapy by augmentation of action of standard anti-cancer drugs.