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Phenothiazine derivatives are well-known anti-psychotic drugs that possess several biological activities including anticancer activity. Much research provides data about its anticancer activity against human glioblastoma cell lines. Unfortunately, to date in vitro studies analyzing the impact of phenothiazines on the viability of human astrocytes have not been performed. However, it is possible to find one study about the viability of neurons and neurons with glia after incubation with perphenazine. Thus, in this study we measured the viability of human astrocytes after 24-, 48-, and 72-hour incubation with perphenazine and prochlorperazine dimaleate using the WST-1 assay. The obtained results suggest that perphenazine is safer for human astrocytes than prochlorperazine dimaleate. Moreover, 24-hour incubation with perphenazine or prochlorperazine did not significantly reduce cellular viability. It is a very important finding since previously we proved that in similar concentrations both drugs reduce the viability of the human glioblastoma U-87 MG cell line by approximately 50%. Therefore, the results suggest that phenothiazines can be used in glioblastoma treatment in concentrations that do not impact human astrocyte viability.

Caffeic acid phenethyl ester (CAPE) belongs to the phenols found in propolis. It has already shown strong antiproliferative, cytotoxic and pro-apoptotic activities against head and neck cancers and against breast, colorectal, lung and leukemia cancer cells. Ovarian cancer is one of the most dangerous gynecological cancers. Its treatment involves intensive chemotherapy with platinum salts and paclitaxel (PTX). The purpose of this study was to evaluate whether the combined use of CAPE and paclitaxel increases the effectiveness of chemotherapeutic agents. The experiment was performed on three ovarian cancer lines: OV7, HTB78, and CRL1572. The effect of the tested compounds was assessed using H-E staining, a wound-healing test, MTT and the cell death detection ELISAPLUS test. The experiment proved that very low doses of PTX (10 nM) showed a cytotoxic effect against all the cell lines tested. Also, the selected doses of CAPE had a cytotoxic effect on the tested ovarian cancer cells. An increase in the cytotoxic effect was observed in the OV7 line after the simultaneous administration of 10 nM PTX and 100 µM CAPE. The increase in the cytotoxicity was dependent on the CAPE dosage (50 vs. 100 µM) and on the duration of the experiment. In the other cell lines tested, the cytotoxic effect of PTX did not increase after the CAPE administration. The administration of PTX together with CAPE increased the percentage of apoptotic cells in the tested ovarian cancer cell lines. Moreover, the simultaneous administration of PTX and CAPE enhanced the anti-migration activity of the chemotherapeutic used in this study.

Prostate cancer is a common cancer in men in older age groups. The WHO forecasts an increase in the incidence of prostate cancer in the coming years. Patients may not respond to treatment, and may not tolerate the side effects of chemotherapy. Compounds of natural origin have long been used in the prevention and treatment of cancer. Flavonoids obtained from natural products, e.g., propolis, are compounds with proven antibacterial and antiviral efficacy which modulate the immune response and may be useful as adjuvants in chemotherapy. The main aim of the present study was to evaluate the cytotoxic and pro-apoptotic properties of selected flavonoids on prostate cancer cells of the LNCaP line. The compounds used in this study were CAPE, curcumin (CUR), and quercetin (QUE). Mitochondrial and lysosome metabolism was assessed by the XTT-NR-SRB triple assay as well as by the fluorescent staining techniques. Staining for reactive oxygen species was performed as well. The experiment showed that each of the tested compounds has a cytotoxic effect on the LNCaP cell line. Different types of cell death were induced by the tested compounds. Apoptosis was induced by quercetin, while autophagy-specific changes were observed after using CAPE. Compounds obtained from other bee products have antiproliferative and cytotoxic activity against LNCaP prostate cancer cells.

Some NK cell subpopulations may be involved in the modulation of fibrogenesis in the liver. The aim of the study was to evaluate the relationship between the number and phenotype of NK cell subsets in peripheral blood (PB) and total NK cell percentage, population density and the degree of liver fibrosis of patients infected with hepatitis C virus (HCV+). The study group consisted of 56 HCV+ patients, divided into two subgroups: patients with mild or moderate fibrosis and patients with advanced liver fibrosis or cirrhosis (F ≥ 3 in METAVIR classification). The preparations were stained with H-E and AZAN staining. NK cells were targeted with anti-CD56 antibody and identified automatically in situ using the DakoVision system. Assessment of different NK cell subsets in PB was performed with the flow cytometry technique. In the PB of HCV+ patients with advanced liver fibrosis, there was a lower proportion of CD62L+; CD62L+/CD94++; CD27+; CD127+/CD27+ and CXCR3+/CD27+ NK subsets, as compared to patients with mild/moderate liver fibrosis. The results also showed no association between total PB NK cell level and total intrahepatic NK cell population density between patients with mild/moderate fibrosis and with advanced liver fibrosis. However, positive correlations between the PB levels of CD94+ and CD62L+ NK cell subsets and the intrahepatic total NK cell percentage and population density in the liver, irrespectively to the extent of fibrosis, were observed. Additionally, positive correlation was found between the PB CXCR3+/CD94+ NK cell percentages and intrahepatic NK cell percentages in patients with advanced hepatic fibrosis. Lower blood availability of specific NK subsets in patients with chronic type C hepatitis might be a cause of progression of liver fibrosis via insufficient control over hepatic stellate 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.

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.

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 IC 50 values more than twice as low as CA. IC 50 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.

Staphylococcus epidermidis is a bacterium that belongs to the human microbiota. It is most plentiful on the skin, in the respiratory system, and in the human digestive tract. Moreover, it is the most frequently isolated microorganism belonging to the group of Coagulase Negative Staphylococci (CoNS). In recent years, it has been recognized as an important etiological factor of mainly nosocomial infections and infections related to the cardiovascular system. On the other hand, Staphylococcus aureus, responsible for in-hospital and out-of-hospital infections, is posing an increasing problem for clinicians due to its growing resistance to antibiotics. Biofilm produced by both of these staphylococcal species in the course of infection significantly impedes therapy. The ability to produce biofilm hinders the activity of chemotherapeutic agents—the only currently available antimicrobial therapy. This also causes the observed significant increase in bacterial resistance. For this reason, we are constantly looking for new substances that can neutralize microbial cells. In the present review, 58 substances of plant origin with antimicrobial activity against staphylococcal biofilm were replaced. Variable antimicrobial efficacy of the substances was demonstrated, depending on the age of the biofilm. An increase in the activity of the compounds occurred in proportion to increasing their concentration. Appropriate use of the potential of plant-derived compounds as an alternative to antibiotics may represent an important direction of change in the support of antimicrobial therapy.

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.

Bee pollen constitutes a natural source of antioxidants such as phenolic acids and flavonoids, which are responsible for its biological activity. Research has indicated the correlation between dietary polyphenols and cardioprotective, hepatoprotective, anti-inflammatory, antibacterial, anticancerogenic, immunostimulating, antianaemic effects, as well as their beneficial influence on osseous tissue. The beneficial effects of bee pollen on health result from the presence of phenolic acids and flavonoids which possess anti-inflammatory properties, phytosterol and linolenic acid which play an anticancerogenic role, and polysaccharides which stimulate immunological activity. Polyphenols are absorbed in the alimentary tract, metabolised by CYP450 enzymes, and excreted with urine and faeces. Flavonoids and phenolic acids are characterised by high antioxidative potential, which is closely related to their chemical structure. The high antioxidant potential of phenolic acids is due to the presence and location of hydroxyl groups, a carboxyl group in the immediate vicinity of ortho-diphenolic substituents, and the ethylene group between the phenyl ring and the carboxyl group. As regards flavonoids, essential structural elements are hydroxyl groups at the C5 and C7 positions in the A ring, and at the C3′ and C4′ positions in the B ring, and a hydroxyl group at the C3 position in the C ring. Furthermore, both, the double bond between C2 and C3, and a ketone group at the C4 position in the C ring enhance the antioxidative potential of these compounds. Polyphenols have an ideal chemical structure for scavenging free radicals and for creating chelates with metal ions, which makes them effective antioxidants in vivo.

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.

Among many infectious diseases, infections caused by pathogens of Staphylococcus species exert a substantial influence upon human health, mainly due to their continuous presence on human skin and mucous membranes. For that reason, an intensive search for new, effective anistaphyloccocal agents can currently be observed worldwide. In recent years, there has been growing interest in nanoparticles, as compounds with potential antibacterial effect. The antibacterial activity of silver containing substances has been well recognized, but thoughtful studies focused on the effect of silver nanoparticles on bacterial biofilm are scarce. The aim of this study was to assess the influence of silver nanoparticles (AgNPs) with particle sizes in the range between 10 and 100 nm, and a concentration range from 1 to 10 µg/mL, upon Staphylococcus epidermidis strains with different biofilm-forming abilities (BFAs). The studies revealed the highest level of antimicrobial activity for AgNPs in relation to S. epidermidis strains with BFA, and what is more, the observed effect was proportional to the increasing particles’ size, and strains not forming biofilm were more susceptible to silver nanoparticles with the smallest examined size, which was 10 nm.

Chemotherapy of breast cancer could be improved by bioactive natural substances, which may potentially sensitize the carcinoma cells’ susceptibility to drugs. Numerous phytochemicals, including propolis, have been reported to interfere with the viability of carcinoma cells. We evaluated the in vitro cytotoxic activity of ethanol extract of propolis (EEP) and its derivative caffeic acid phenethyl ester (CAPE) towards two triple-negative breast cancer (TNBC) cell lines, MDA-MB-231 and Hs578T, by implementation of the MTT and lactate dehydrogenase (LDH) assays. The morphological changes of breast carcinoma cells were observed following exposure to EEP and CAPE. The IC50 of EEP was 48.35 µg∙mL−1 for MDA-MB-23 cells and 33.68 µg∙mL−1 for Hs578T cells, whereas the CAPE IC50 was 14.08 µM and 8.01 µM for the MDA-MB-231 and Hs578T cell line, respectively. Here, we report that propolis and CAPE inhibited the growth of the MDA-MB-231 and Hs578T lines in a dose-dependent and exposure time-dependent manner. EEP showed less cytotoxic activity against both types of TNBC cells. EEP and, particularly, CAPE may markedly affect the viability of breast cancer cells, suggesting the potential role of bioactive compounds in chemoprevention/chemotherapy by potentiating the action of standard anti-cancer drugs.

Alcohol increases the risk of carcinoma originated from oral epithelium, but the biological effects of ultra-low doses of ethanol on existing carcinoma cells in combination with natural substances are still unclear. A role for ethanol (EtOH), taken in small amounts as an ingredient of some beverages or mouthwashes to change the growth behavior of established squamous cell carcinoma, has still not been examined sufficiently. We designed an in vitro study to determine the effect of caffeic acid (CFA) on viability and migration ability of malignant oral epithelial keratinocytes, exposed to ultra-low concentrations (maximum 100 mmol/L) EtOH. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-dimethyltetrazolium bromide) and LDH (lactate dehydrogenase) assays were used to assess the cytotoxic effect of EtOH/CFA and the viability of squamous carcinoma SCC-25 cells (ATCC CRL-1628, mobile part of the tongue). Tested EtOH concentrations were: 2.5, 5, 10, 25, 50, and 100 mmol/L, along with an equal CFA concentration of 50 μmol/L. Carcinoma cells’ migration was investigated by monolayer “wound” healing assay. We demonstrated that very low concentrations of EtOH ranging between 2.5 and 10 mmol/L may induce the viability of oral squamous cell carcinoma cells, while the results following addition of CFA reveal an antagonistic effect, attenuating pro-proliferative EtOH activity. The migration rate of oral squamous carcinoma cells can be significantly inhibited by the biological activity of caffeic acid.

Synergistic interactions between commonly used antibiotics and natural bioactive compounds may exhibit therapeutic benefits in a clinical setting. Berberine, an isoquinoline-type alkaloid isolated from many kinds of medicinal plants, has proven efficacy against a broad spectrum of microorganisms. The aim of the presented work was to assess the antibacterial activity of berberine chloride in light of the effect exerted by common antibiotics on fourteen reference strains of Staphylococccus spp., and to evaluate the magnitude of interactions of berberine with these antistaphylococcal antibiotics. In our study minimum inhibitory concentrations (MIC) of berberine chloride against CoNS ranged from 16 to 512 µg/mL. The most noticeable effects were observed for S. haemolyticus ATCC 29970, S. epidermidis ATCC 12228, S. capitis subsp. capitis ATCC 35661, S. galinarium ATCC 700401, S. hominis subsp. hominis ATCC 27844, S. intermedius ATCC 29663 and S. lugdunensis ATCC 49576. The most significant synergistic effect was noticed for berberine in combination with linezolid, cefoxitin and erythromycin. The synergy between berberine and antibiotics demonstrates the potential application of compound combinations as an efficient, novel therapeutic tool for antibiotic-resistant bacterial infections.

Medicines of biogenic origin with micro-organic, regenerative and analgesic properties are becoming more and more significant in the treatment of burn wounds. These properties are found in apitherapeutics such as propolis and honey—products collected and processed by a honey bee. Their effect on the course of the healing processes is multidirectional. The aim of the study was a histopathological and biochemical analysis of the processes of scar formation in experimentally evoked burn wounds in white pigs treated with the 1% and 3% Sepropol balms containing standardized extracts of propolis and honey. The results were compared with the therapeutic effects obtained with dermazin cream (1% silver sulfadiazine). The level of collagen was determined in the wounds treated with 1% and 3% Sepropol and compared with the collagen level in healthy skin and wounds treated with dermazin. Granulation and regenerated epithelium formation times were compared, with the 3% Sepropol being by far the most effective. The 3% Sepropol also increased the collagen level to 116% with the control sub-groups scoring between 80% and 98%. The results show the healing process of burn wounds in pigs treated with the Sepropol balm starts earlier and has a faster course than the standard dermazin therapy.

The objective of this study was to assess in vitro the antimicrobial activity of ethanolic extract of Polish propolis (EEPP) against methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA) clinical isolates. The combined effect of EEPP and 10 selected antistaphylococcal drugs on S. aureus clinical cultures was also investigated. EEPP composition was analyzed by a High Performance Liquid Chromatography (HPLC) method. The flavonoid compounds identified in Polish Propolis included flavones, flavonones, flavonolols, flavonols and phenolic acids. EEPP displayed varying effectiveness against twelve S. aureus strains, with minimal inhibitory concentration (MIC) within the range from 0.39 to 0.78 mg/mL, determined by broth microdilution method. The average MIC was 0.54 ± 0.22 mg/mL, while calculated MIC50 and MIC90 were 0.39 mg/mL and 0.78 mg/mL, respectively. The minimum bactericidal concentration (MBC) of the EEPP ranged from 0.78 to 3.13 mg/mL. The in vitro combined effect of EEPP and 10 antibacterial drugs was investigated using disk diffusion method-based assay. Addition of EEPP to cefoxitin (FOX), clindamycin (DA), tetracycline (TE), tobramycin (TOB), linezolid (LIN), trimethoprim+sulfamethoxazole (SXT), penicillin (P), erythromycin (E) regimen, yielded stronger, cumulative antimicrobial effect, against all tested S. aureus strains than EEPP and chemotherapeutics alone. In the case of ciprofloxacin (CIP) and chloramphenicol (C) no synergism with EEPP was observed.

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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.

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.

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.

The authors wish to make the following corrections to this paper: [...]