Antiproliferative Potential of Pomegranate Peel Extract in MDA-MB Breast Cancer Cell Lines

Adenoviral vectors with E1A regulated by tumor-specific promoters are selectively cytolytic for breast cancer and melanoma.

The current study focuses on Punica granatum L. (pomegranate) peel and peel extract and their use as functional foods, food additives, or physiologically active constituents in nutraceutical formulations. The pomegranate peel extract is a good source of bioactive substances needed for the biological activity of the fruit, including phenolic acids, minerals, flavonoids (anthocyanins), and hydrolyzable tannins (gallic acid). The macromolecules found in pomegranate peel and peel extract have been recommended as substitutes for synthetic nutraceuticals, food additives, and chemo-preventive agents because of their well-known ethno-medical significance and chemical properties. Moreover, considering the promises for both their health-promoting activities and chemical properties, the dietary and nutraceutical significance of pomegranate peel and pomegranate peel extract appears to be underestimated. The present review article details their nutritional composition, phytochemical profile, food applications, nutraceutical action, and health benefits.

Background: Denture stomatitis, caused primarily by Candida albicans overgrowth, is a common oral health issue among denture wearers. Maintaining denture hygiene is crucial for prevention. This study investigated the efficacy of red pomegranate (Punica granatum L.) peel and fruit extracts as natural denture cleansers compared to sodium bicarbonate, a standard denture cleansing agent. Methods: Heat-cured acrylic resin plates were fabricated and contaminated with C. albicans. Samples were divided into four groups and soaked for 8 hours in: 75% pomegranate peel extract, 75% pomegranate fruit extract, 5% sodium bicarbonate solution (positive control), and aquadest (negative control). C. albicans colony counts were performed using the spread plate technique and colony counter. Data were analyzed using Kruskal-Wallis and Mann-Whitney tests. Results: Both pomegranate peel and fruit extracts significantly reduced C. albicans growth compared to the negative control (p<0.05). The peel extract showed comparable efficacy to sodium bicarbonate (p>0.05), while the fruit extract demonstrated slightly lower but still substantial antifungal activity. Conclusion: Red pomegranate peel and fruit extracts hold promise as natural denture cleansers for inhibiting C. albicans and potentially preventing denture stomatitis. Further research is warranted to evaluate their long-term effects on denture materials and clinical efficacy.

Breast cancer (BCa) and prostate cancer (PCa) are both hormone driven cancers with similar etiology and tumor microenvironment inflammation promotes BCa and PCa progression. Interleukin-1 (IL-1) is an inflammatory cytokine present in the tumor microenvironment and IL-1 is elevated in BCa and PCa patient tumor and/or blood serum and correlates with poor prognosis. We have shown that IL-1 represses the BCa and PCa therapeutic targets, Estrogen Receptor Alpha (ERa) and Androgen Receptor (AR), respectively, in PCa and BCa cell lines; yet the cells remain viable. Thus, IL-1 may promote treatment resistance and disease progression. The pro-survival protein Sequestome-1 (SQSMT1/p62) is also upregulated in both BCa and PCa cell lines exposed to IL-1, suggesting that BCa and PCa cells have evolved a shared response to IL-1 and hormone receptor loss. RNA sequencing of an IL-1-treated PCa cell line revealed an IL-1-modulated gene suite predicted to confer AR-independent tumorigenicity. We performed RT-qPCR in PCa cell lines for several select genes to confirm the RNA sequencing results and given the similar etiology and IL-1 regulation of ERa, AR, and p62 expression in BCa and PCa cell lines, we presumed that our select genes would be similarly regulated by IL-1 in BCa cells. However, outside of ERa, AR, and p62 expression, our select genes did not show similar IL-1 regulation in BCa cell lines, suggesting that IL-1 regulates a unique set of genes that could contribute to ERa-independent tumorigenicity in BCa cells. Therefore, to identify a BCa-specific IL-1-modulated gene suite, we performed RNA sequencing on an IL-1-treated ERα+ BCa cell line and compared gene expression changes with 1) basal gene expression in an ERa- BCa cell line and 2) our IL-1-modulated PCa-specific gene suite. Our bioinformatics analysis revealed pathways that are predicted to promote ERa-independent tumorigenicity in BCa cells and investigations are underway to demonstrate the functional significance of our gene expression data. Taken together, our studies provide insight into the mechanistic function of IL-1 in PCa and BCa resistance to hormone receptor-targeted therapies and tumor progression. Citation Format: Afshan Fathima Nawas, Mohammed Kanchwala, Shayna Thomas-Jardin, Vanessa Anunobi, Ally Wong, Chao Xing, Nikki Delk. Identification of Interleukin-1 (IL-1) induced gene expression pattern in breast cancer (BCa) cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3444.

Pomegranate peel is food waste unfit to eat parts obtained during the production of pomegranate juice. The aim of this work is to study the effect of four different solvents (ethanol, isopropanol, hot and cold water) on phytochemicals screening, total phenolics content, total flavonoid content and antioxidants activity in pomegranate peels, as well as identification of phenolic compounds in extracts by HPLC. Phenolics, flavonoids, alkaloids, saponins, tannins, steroids and terpenoids were detected in all extracts. The highest total phenolics and total flavonoids were observed in ethanol extract of pomegranate peels (161.5 mg GAE/g and 70.65 mg Rutin/g), respectively. Furthermore, the ethanol extract of pomegranate peels showed the highest DPPH scavenging activity with the lowest IC50 value 14.6 μg/ml compared to other extracts. The high antioxidant activities may be due to the high contents of phenolics and flavonoids in pomegranate peel ethanol extract. HPLC analysis was used for the identification and quantitative determination of phenolic compounds in pomegranate peels extracts. The results revealed nine polyphenolic compounds including protocatechuic acid, p-coumaric acid, caffeic acid, ellagic acid, cinnamic acid, quinic acid, benzoic acid, syringic acid and iso-ferulic acid in pomegranate peels extracts. The obtained results confirmed that ethanol extract was the most abundant of phenolics compounds as compared to the other extracts. Finally, it can be concluded that pomegranate peel extracts can be used in various fields for being rich in natural antioxidants that have a medicinal and therapeutic impact.

The experiment was undertaken to evaluate the effect of pomegranate (Punica granatum) juice and peel extract on antioxidant status in streptozotocin induced diabetic rats. The study included seven treatment groups comprising of ten albino Wistar rats each. The various groups in this study included normal control Group I (NC), diabetic control (Group II (DC), diabetic rats treated with metformin at the rate of 500 mg/kg bw Group III (MF), diabetic rats treated with pomegranate fresh juice at 1mL/day Group IV(PJ), diabetic rats treated with pomegranate peel extracts at 100mg/day Group V (PPE), diabetic rats treated with pomegranate fresh juice 1mL + pomegranate peel extracts (100mg) at 50 per-cent dosage and metformin (half dose) Group-VI (PJ+PPE+MF 50%), diabetic rats treated with pomegranate fresh juice (0.5mL) + pomegranate peel extracts extract (50mg) at 50 per-cent dosage and metformin (half dose) (Group-VII (PJ+PPE @ 50% +MF 50%). Antioxidant status of rats was evaluated by estimating product of oxidative injury (MDA) and endogenous antioxidant enzymes (CAT, SOD and GPx) in the liver on 3rd, 15th, 30th and 45th day. All the antioxidant enzymes (CAT, SOD and GPx) markedly reduced in diabetic control (DC) rats. However, treatment groups treated with pomegranate juice or pomegranate peel extract (Group IV to VII) individually or in combination showed a significant improvement in all the antioxidant enzymes (CAT, SOD and GPx) compared to the diabetic control rats. It was observed that metformin substantially alleviated the effects of STZ in diabetic rats compared to all the treatment groups. Pomegranate peel extract was observed to have marginally improve antidiabetic effects compared to pomegranate juice. Combination of pomegranate juice and pomegranate peel extract with metformin at half dose and full dose also alleviated STZ induced diabetic effects significantly. However, there was no dose dependent and synergistic effect. It could be inferred that bioactive compounds of pomegranate juice and pomegranate peel extract have antiperoxidative effect due to their ability to scavenge free radicals or chelate metal ions in STZ induced rats.

The pro-proliferative effect of interferon-γ in breast cancer cell lines is dependent on stimulation of ASCT2-mediated glutamine cellular uptake

Spontaneous Formation of Tumorigenic Hybrids between Breast Cancer and Multipotent Stromal Cells Is a Source of Tumor Heterogeneity

The medicinal and commercial value of pomegranate peel is attributed to its rich content of phenolic compounds, yet little is known about their concentrations and biological activity across different ripening stages. Pomegranate peels at different growth stages 1–3 (40, 80, and 120 days after fruit appearance respectively) were collected, dried, and macerated with 90% methanol. Stage 2 and stage 3 extract showed significant antimicrobial activity against S. aureus, and L. monocytogenes. Further, stage 2 extract showed highest efficacy against lung, breast, and liver cancer cells with IC50 values of 19.76 ± 1.3, 24.28 ± 6.99, and 16.04 ± 2.78 µg/mL, respectively. Molecular docking, and simulation further confirmed the antimicrobial and cytotoxic activity of the most prominent stage 2 phytoconstituent (γ-Sitosterol). The study indicates that stage 2 pomegranate peel extract has potential as a safe and natural antimicrobial and cytotoxic agent. However, additional in vitro and in vivo testing is needed to validate these results.

In vivo study of pomegranate (Punica granatum) peel extract efficacy against Giardia lamblia in infected experimental mice

Summary Nowadays, uncontrolled and frequent use of antibiotics may cause emergence of microbial resistance among pathogenic agents. Therefore, the use of new synthetic and natural antimicrobial compounds is inevitable. One source of natural compounds in this respect comes from plants. The purpose of this study was to examine the antibacterial effects of peel extracts from sour and sweet pomegranate. Methanolic extracts of sour and sweet pomegranate peels and aqueous solutions of tetracycline and chloramphenicol were prepared. Antibiogram tests using disk diffusion technique and serial dilution method were performed against ten pathogenic bacteria isolated from animals, and relative minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values were also determined for the above compounds. The greatest zone of inhibition induced by the action of pomegranate peel extracts was obtained for Staphylococcus aureus (about 25 mm) and the smallest zone of inhibition was obtained for Pasteurella multocida (about 9 mm). In addition, the lowest MIC and MBC values of pomegranate peel extract were obtained for Staphylococcus aureus (7.8 and 62.5 mg/ml, respectively). Results of serial dilution tests indicate that bactericidal effect of sour pomegranate peel extract was more than that for sweet pomegranate peel extract; and sweet pomegranate peel extract exerts a bacteriostatic action against bacteria. The antibacterial effect was greater against Gram-positive bacteria compared to that for the Gram-negative bacteria. Effects of these extracts were considerably lower than those for tetracycline and chloramphenicol. In conclusion, methanolic extracts of pomegranate peels exhibit relatively good bacteriostatic and bactericidal effects.

Background and objectives Indoles derivatives are natural products, which are well known for their anticancer activity due to its ability to induce cell death for many cancer cell lines. The aim of this study is to synthesize some new heterocyclic compounds derived from 1H-indole-3-carbaldehyde, malononitrile, and different reagents namely: active methylene derivatives, amine derivatives, and resorcinol. The newly synthesized derivatives were prepared and confirmed by their IR, Mass, and 1NMR spectra; and were also tested for their antiproliferative potency towards human breast cancer (MCF-7) and normal murine fibroblast (BALB/3T3) cell lines. Materials and methods The synthesis of new indole derivatives (3a-e) was achieved by the three-component reactions of 1H-indole-3-carbaldehyde (1), ethyl 3-oxobutanoate, 5,5-dimethyl cyclohexane-1,3-dione (Dimidone), barbituric, thiobarbituric acid, and cyclohexanone (2a-e), respectively; and malononitrile in the presence of triethylamine. Compound (4) was afforded by fusing of compound (3a) with thiourea. Also, compounds (5a, b) were yielded by the grinding of compounds (3c, d) with formic acid. On the other side, one-pot synthesis of 7a-d has been achieved via three-component of 1H-indole-3-carbaldehyde (1), and malononitrile in the presence of amine derivatives (namely, 2,4-dinitroaniline, 3-nitroaniline, 3-bromoaniline, and 4-methoxyaniline) (6a-d), respectively, by condensation. Also, compounds (8, 9) were obtained by refluxing of compounds (7a, b) with formic acid. Compound (10) was afforded by condensing the mixture of 1H-indole-3-carbaldehyde (1) with resorcinol in the presence of malononitrile and triethylamine. The newly synthesized derivatives were tested for their antiproliferative potency towards human breast cancer (MCF-7) and normal murine fibroblast (BALB/3T3) cell lines. Results indicated that they showed significant in-vitro antiproliferative activity. Results and conclusion A novel protocol for the preparation of indole derivatives (3a-e) using the three-component reactions of 1H-indole-3-carbaldehyde (1) with active methylene compounds namely: ethyl 3-oxobutanoate, 5, 5-dimethy cyclohexane-1, 3-dione (Dimidone), barbituric acid, thiobarbituric acid, and cyclohexanone (2a-e); and malononitrile in ethanol and triethylamine as catalyst were proceeded in one step. Also, compounds (3a, 3c, d) were reacted with thiourea/and formic acid, respectively, to give compounds (4 and 5a, b). The 3-indole derivatives (7a-d) were formed via condensation of the amine derivatives (6a-d) with indole aldehydes (1) and malononitrile. Compounds (8 and 9) were afforded by condensation of compounds (7b, c) with formic acid, 2-amino-chromene (10) was produced by reaction of resorcinol, 1H-indole-3-carbaldehyde (1), and malononitrile. The in-vitro study showed that most of the prepared compounds gave similar activity towards breast cancer cell line MCF-7 but did not reveal the cytotoxic potency against normal cell line. This means that most of these compounds kill cancer cells but have no or slight effects on normal cells. The newly synthesized derivatives were tested for their antiproliferative potency towards human breast cancer (MCF-7) and normal murine fibroblast (BALB/3T3) cell lines. The results showed that the in-vitro antiproliferative activity of the prepared compounds was significant and could thus be investigated for further in vivo and pharmacokinetic studies.

Effects of pomegranate peel and artichoke leaf aqueous extracts on biochemical, microbiological and sensorial quality of sardine fillets was investigated during marination and storage for 90days. Sardine fillets were marinated with 4% acetic acid, 10% NaCl and either 5% pomegranate peel extracts or 5% artichoke leaf extracts. The control sample was marinated with only 4% acetic acid and 10% NaCl. The antimicrobial activity of pomegranate peel and artichoke leaf extracts led to reduce total viable counts and total coliform during marination and storage. Samples marinated with pomegranate peel and artichoke leaves showed better oxidative stability and higher content of polyunsaturated fatty acids. Higher values of free fatty acids and histamine were found in control samples, whereas adding extracts of pomegranate peel or artichoke leaves significantly decreased total volatile basic nitrogen and trimethylamine during storage. Greater color and appearance scores were found for samples marinated with pomegranate peel and artichoke leaf extracts than the control samples.

In recent years, the increase in cancer morbidity and mortality has presented scientists with a major challenge in developing new therapeutic agents against cancer cells. This study aims to characterize the anticancer effects of copper oxide nanoparticles (NPs) conjugated with Lapatinib (CuO@Lapatinib) on breast and lung cancer cell lines. The physicochemical properties of the NPs were characterized by fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), and zeta potential analyses. The antiproliferative potential of the NPs in the breast (MDA-MB-231) and lung (A549) cancer cell lines and a normal cell line (MRC5) was investigated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Flow cytometry and Hoechst staining were used to evaluate cell apoptosis and cell cycle analysis. The reactive oxygen species (ROS) levels in the treated and control cells were also determined. The NPs were spherical, with a size range of 20-59nm, a DLS size of 338nm, and a zeta potential of -42.9 mV. The half maximal inhibitory concentration (IC50) of CuO@Lapatinib NPs for the normal, breast cancer, and lung cancer cell lines was 105, 98, and 87 µg/ml, respectively. Treatment with CuO@Lapatinib NPs caused considerable apoptosis induction in breast cancer (from 0.65% to 68.96%) and lung cancer cell lines (from 1.11% to 44.11%). Also, an increased level of cell cycle arrest at the S phase was observed in both cancer cell lines. The ROS level in the breast and lung cancer cell lines after treatment with CuO@Lapatinib NPs increased by 3.45 and 21.04 folds, respectively. Nuclear morphological alterations, including chromatin condensation and fragmentation, were observed in both cancer cell lines. This study indicates CuO@Lapatinib is a potent antiproliferative compound with more efficient inhibitory effects on lung cancer than breast cancer cells, which can be related to the higher ROS generation in the A549 cell line.

Regulators of Mitotic Arrest and Ceramide Metabolism Are Determinants of Sensitivity to Paclitaxel and Other Chemotherapeutic Drugs