Preparation of Black pepper (Piper nigrum L.) essential oil nanoparticles and its antitumor activity on triple negative breast cancer in vitro
Mengying Zhang
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Search for more papers by this authorBeibei Qiu
Department of Pathology, Feicheng Hospital affiliated to Shandong First Medical University, Feicheng, China
Search for more papers by this authorMengjia Sun
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Search for more papers by this authorYunfei Wang
Quality Assurance Department, Shandong Xinhua Pharmaceutical Company Limited, Zibo, China
Search for more papers by this authorMeijiao Wei
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Search for more papers by this authorCorresponding Author
Yanling Gong
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Correspondence
Yanling Gong, Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao 266042, China.
Email: [email protected]
Meixing Yan, Qingdao Women and Children's Hospital, Qingdao 266011, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Meixing Yan
Department of Pharmacy, Qingdao Women and Children's Hospital, Qingdao, China
Correspondence
Yanling Gong, Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao 266042, China.
Email: [email protected]
Meixing Yan, Qingdao Women and Children's Hospital, Qingdao 266011, China.
Email: [email protected]
Search for more papers by this authorMengying Zhang
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Search for more papers by this authorBeibei Qiu
Department of Pathology, Feicheng Hospital affiliated to Shandong First Medical University, Feicheng, China
Search for more papers by this authorMengjia Sun
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Search for more papers by this authorYunfei Wang
Quality Assurance Department, Shandong Xinhua Pharmaceutical Company Limited, Zibo, China
Search for more papers by this authorMeijiao Wei
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Search for more papers by this authorCorresponding Author
Yanling Gong
Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao, China
Correspondence
Yanling Gong, Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao 266042, China.
Email: [email protected]
Meixing Yan, Qingdao Women and Children's Hospital, Qingdao 266011, China.
Email: [email protected]
Search for more papers by this authorCorresponding Author
Meixing Yan
Department of Pharmacy, Qingdao Women and Children's Hospital, Qingdao, China
Correspondence
Yanling Gong, Department of Pharmacy, College of Chemical Engineering, Qingdao University of Science and Technology, 53 Zhengzhou Road, Qingdao 266042, China.
Email: [email protected]
Meixing Yan, Qingdao Women and Children's Hospital, Qingdao 266011, China.
Email: [email protected]
Search for more papers by this authorAbstract
The active compounds isolated from Black pepper have anticancer effects, but the bioactivity of Black pepper essential oil (BP-EO) is rarely studied. BP-EO has poor stability and a suitable dose form should be prepared for in vivo delivery. Triple negative breast cancer (TNBC) has attracted more and more attention due to its high mitotic index, high metastasis rate and poor prognosis. In this study, the composition of BP-EO was analyzed by gas chromatography–mass spectrometry (GC–MS), and nanoparticles (NPs) loaded with BP-EO were prepared by nanoprecipitation method using Eudragit L100 as a carrier. We investigated the preparation, characterization, stability and in vitro release of nanoparticles. MTT assay, cell wound healing, Transwell invasion assay and Western blot were used to study the anti-tumor effect and mechanism of MDA-MB-231 cells. The GC–MS analysis identified a total of 33 compounds among which alkenes account for 63.55%. The prepared BP-EO NPs exhibited nanoscale morphology, good stability and pH-responsive and sustained release character which is suitable for in vivo delivery. BP-EO NPs significantly inhibited the proliferation, migration and invasion of MDA-MB-231 cells. Furthermore, BP-EO NPs significantly inhibited the expressions of Wnt and β-catenin and significantly activated the expression of GSK-3β in MDA-MB-231 cells. Therefore, BP-EO NPs prepared in this study provide a new effective strategy for the treatment of TNBC.
Practical applications
Black pepper is rich in essential oil and has excellent antioxidant and antibacterial activities. However, the anti-tumor activity of BP-EO has not been studied. In this study, we found that BP-EO has excellent anticancer activity. To achieve effective encapsulation of black pepper essential oil and an excellent anti-triple negative breast cancer activity, nanoparticles loaded with BP-EO were prepared using Eudragit L100 as the carrier by the nanoprecipitation method. The in vitro study revealed that BP-EO NPs inhibited proliferation, migration and invasion of MDA-MB-231 cells via inhibiting the Wnt/β-Catenin signaling pathway. This study provides new ideas and innovations for the treatment of invasive triple negative breast cancer in the future. At the same time, we will further reveal the application potential, pharmacokinetic characteristics and precise mechanism of BP-EO NPs in vivo in subsequent studies.
CONFLICT OF INTEREST
The authors declared that they have no conflict of interest.
Open Research
DATA AVAILABILITY STATEMENT
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
REFERENCES
- Akkoc, Y., & Gozuacik, D. (2021). Autophagy and hepatic tumor microenvironment associated dormancy. Journal of Gastrointestinal Cancer, 52, 1277–1293.
- Amado, N. G., Fonseca, B. F., Cerqueira, D. M., Neto, V. M., & Abreu, J. G. (2011). Flavonoids: Potential Wnt/beta-catenin signaling modulators in cancer. Life Sciences, 89, 545–554.
- Amado, N. G., Predes, D., Moreno, M. M., Carvalho, I. O., Mendes, F. A., & Abreu, J. G. (2014). Flavonoids and Wnt/beta-catenin signaling: potential role in colorectal cancer therapies. International Journal of Molecular Sciences, 15, 12094–12106.
- Bag, A., & Chattopadhyay, R. R. (2015). Evaluation of synergistic antibacterial and antioxidant efficacy of essential oils of spices and herbs in combination. PLoS One, 10, e0131321.
- Bagnyukova, T., Serebriiskii, I. G., Zhou, Y., Hopper-Borge, E. A., Golemis, E. A., & Astsaturov, I. (2010). Chemotherapy and signaling: How can targeted therapies supercharge cytotoxic agents? Cancer Biology & Therapy, 10, 843–857.
- Breuer, E. K., Fukushiro-Lopes, D., Dalheim, A., Burnette, M., Zartman, J., Kaja, S., Wells, C., Campo, L., Curtis, K. J., Romero-Moreno, R., Littlepage, L. E., Niebur, G. L., Hoskins, K., Nishimura, M. I., & Gentile, S. (2019). Potassium channel activity controls breast cancer metastasis by affecting beta-catenin signaling. Cell Death & Disease, 10, 180.
- Butt, M. S., Pasha, I., Sultan, M. T., Randhawa, M. A., Saeed, F., & Ahmed, W. (2013). Black pepper and health claims: A comprehensive treatise. Critical Reviews in Food Science and Nutrition, 53, 875–886.
- Camacho, S. A., Kobal, M. B., Moreira, L. G., Bistaffa, M. J., Roque, T. C., Pazin, W. M., Toledo, K. A., Oliveira, O. N., Jr., & Aoki, P. H. B. (2021). The efficiency of photothermal action of gold shell-isolated nanoparticles against tumor cells depends on membrane interactions. Colloids and Surfaces B: Biointerfaces, 211, 112301.
- Castellanos-Rubio, I., Arriortua, O., Marcano, L., Rodrigo, I., Iglesias-Rojas, D., Baron, A., Olazagoitia-Garmendia, A., Olivi, L., Plazaola, F., Fdez-Gubieda, M. L., Castellanos-Rubio, A., Garitaonandia, J. S., Orue, I., & Insausti, M. (2021). Shaping up Zn-doped magnetite nanoparticles from mono- and bimetallic oleates: The impact of Zn content, Fe vacancies, and morphology on magnetic hyperthermia performance. Chemistry of Materials, 33, 3139–3154.
- Chae, W. J., & Bothwell, A. L. M. (2018). Canonical and non-canonical Wnt signaling in immune cells. Trends in Immunology, 39, 830–847.
- Dai, B., Fan, M., Yu, R., Su, Q., Wang, B., Yang, T., Liu, F., & Zhang, Y. (2020). Novel diphenyl urea derivative serves as an inhibitor on human lung cancer cell migration by disrupting EMT via Wnt/beta-catenin and PI3K/Akt signaling. Toxicology in Vitro, 69, 105000.
- Damke, G., Souza, R. P., Montanha, M. C., Damke, E., Goncalves, R. S., Cesar, G. B., Kimura, E., Caetano, W., Hioka, N., & Consolaro, M. E. L. (2020). Selective photodynamic effects on breast cancer cells provided by p123 pluronic(R)- based nanoparticles modulating hypericin delivery. Anti-Cancer Agents in Medicinal Chemistry, 20, 1352–1367.
- de Almeida, G. C., Oliveira, L. F. S., Predes, D., Fokoue, H. H., Kuster, R. M., Oliveira, F. L., Mendes, F. A., & Abreu, J. G. (2020). Piperine suppresses the Wnt/beta-catenin pathway and has anti-cancer effects on colorectal cancer cells. Scientific Reports, 10, 11681.
- Dong, Y., & Feng, S. S. (2004). Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs. Biomaterials, 25, 2843–2849.
- Fan, Y., Zhao, X., Ma, J., & Yang, L. (2021). LncRNA GAS5 competitively combined with miR-21 regulates PTEN and influences EMT of peritoneal mesothelial cells via Wnt/beta-catenin signaling pathway. Frontiers in Physiology, 12, 654951.
- Froiio, F., Ginot, L., Paolino, D., Lebaz, N., Bentaher, A., Fessi, H., & Elaissari, A. (2019). Essential oils-loaded polymer particles: Preparation, characterization and antimicrobial property. Polymers, 11, 1017.
- Froiio, F., Mosaddik, A., Morshed, M. T., Paolino, D., Fessi, H., & Elaissari, A. (2019). Edible polymers for essential oils encapsulation: Application in food preservation. Industrial and Engineering Chemistry Research, 58, 20932–20945.
- Gao, Y., Bai, C., Zheng, D., Li, C., Zhang, W., Li, M., Guan, W., & Ma, Y. (2016). Combination of melatonin and Wnt-4 promotes neural cell differentiation in bovine amniotic epithelial cells and recovery from spinal cord injury. Journal of Pineal Research, 60, 303–312.
- Garrido-Castro, A. C., Lin, N. U., & Polyak, K. (2019). Insights into molecular classifications of triple-negative breast cancer: Improving patient selection for treatment. Cancer Discovery, 9, 176–198.
- Ghosh, S., Kumar, A., Sachan, N., & Chandra, P. (2021). Anxiolytic and antidepressant-like effects of essential oil from the fruits of Piper nigrum Linn. (Black pepper) in mice: Involvement of serotonergic but not GABAergic transmission system. Heliyon, 7, e06884.
- Guo, Y., Wei, L., Zhou, Y., Lu, N., Tang, X., Li, Z., & Wang, X. (2020). Flavonoid GL-V9 induces apoptosis and inhibits glycolysis of breast cancer via disrupting GSK-3beta-modulated mitochondrial binding of HKII. Free Radical Biology & Medicine, 146, 119–129.
- He, X., Li, J., An, S., & Jiang, C. (2013). pH-sensitive drug-delivery systems for tumor targeting. Therapeutic Delivery, 4, 1499–1510.
- Huang, M., Zhang, D., Wu, J. Y., Xing, K., Yeo, E., Li, C., Zhang, L., Holland, E., Yao, L., Qin, L., Binder, Z. A., O'Rourke, D. M., Brem, S., Koumenis, C., Gong, Y., & Fan, Y. (2020). Wnt-mediated endothelial transformation into mesenchymal stem cell-like cells induces chemoresistance in glioblastoma. Science Translational Medicine, 12, eaay7522.
- Huang, Z. Y., Song, Y. N., Pang, Z. Q., Zhang, B., Yang, H. B., Shi, H. T., Chen, J., Gong, U., Qian, J. Y., & Ge, J. B. (2017). Targeted delivery of thymosin beta 4 to the injured myocardium using CREKA-conjugated nanoparticles. International Journal of Nanomedicine, 12, 3023–3036.
- Jiang, Y., Krishnan, N., Zhou, J., Chekuri, S., Wei, X., Kroll, A. V., Yu, C. L., Duan, Y., Gao, W., Fang, R. H., & Zhang, L. (2020). Engineered cell-membrane-coated nanoparticles directly present tumor antigens to promote anticancer immunity. Advanced Materials, 32, e2001808.
- Kato, Y., Ozawa, S., Miyamoto, C., Maehata, Y., Suzuki, A., Maeda, T., & Baba, Y. (2013). Acidic extracellular microenvironment and cancer. Cancer Cell International, 13, 89.
- Kim, C., Cho, S. K., Kapoor, S., Kumar, A., Vali, S., Abbasi, T., Kim, S. H., Sethi, G., & Ahn, K. S. (2014). beta-Caryophyllene oxide inhibits constitutive and inducible STAT3 signaling pathway through induction of the SHP-1 protein tyrosine phosphatase. Molecular Carcinogenesis, 53, 793–806.
- Lammari, N., Demautis, T., Louaer, O., Meniai, A. H., Casabianca, H., Bensouici, C., Devouassoux, G., Fessi, H., Bentaher, A., & Elaissari, A. (2021). Nanocapsules containing Saussurea lappa essential oil: Formulation, characterization, antidiabetic, anti-cholinesterase and anti-inflammatory potentials. International Journal of Pharmaceutics, 593, 120138.
- Lammari, N., Froiio, F., Louaer, M., Cristiano, M. C., Bensouici, C., Paolino, D., Louaer, O., Meniai, A. H., & Elaissari, A. (2020). Poly(ethyl acrylate-co-methyl methacrylate-co-trimethylammoniethyl methacrylate chloride) (Eudragit RS100) nanocapsules as nanovector carriers for Phoenix dactylifera L. seeds oil: A versatile antidiabetic agent. Biomacromolecules, 21, 4442–4456.
- Leão, A. D., Alvarez-Lorenzo, C., & Soares-Sobrinho, J. L. (2020). One-pot synthesis of the organomodified layered double hydroxides - glibenclamide biocompatible nanoparticles. Colloids and Surfaces B: Biointerfaces, 193, 111055.
- Li, Y., Xiao, Y., Lin, H. P., Reichel, D., Bae, Y., Lee, E. Y., Jiang, Y., Huang, X., Yang, C., & Wang, Z. (2019). In vivo beta-catenin attenuation by the integrin alpha5-targeting nano-delivery strategy suppresses triple negative breast cancer stemness and metastasis. Biomaterials, 188, 160–172.
- Liao, W., Badri, W., Dumas, E., Ghnimi, S., Elaissari, A., Saurel, R., & Gharsallaoui, A. (2021). Nanoencapsulation of essential oils as natural food antimicrobial agents: An overview. Applied Sciences, 11, 5778.
- Liao, W., Dumas, E., Ghnimi, S., Elaissari, A., & Gharsallaoui, A. (2021). Effect of emulsifier and droplet size on the antibacterial properties of emulsions and emulsion-based films containing essential oil compounds. Journal of Food Processing and Preservation, 45, 0145–8892.
- Lin, Y., Lin, F., Anuchapreeda, S., Chaiwongsa, R., Duangmano, S., Ran, B., & Pornprasert, S. (2021). Effect of miR-133b on progression and cisplatin resistance of triple-negative breast cancer through FGFR1-Wnt-beta-catenin axis. American Journal of Translational Research, 13, 5969–5984.
- Liu, J., Huang, Y., Kumar, A., Tan, A., Jin, S., Mozhi, A., & Liang, X. J. (2014). pH-sensitive nano-systems for drug delivery in cancer therapy. Biotechnology Advances, 32, 693–710.
- Mi, Y., Chen, Y., Gu, G., Miao, Q., Tan, W., Li, Q., & Guo, Z. (2021). New synthetic adriamycin-incorporated chitosan nanoparticles with enhanced antioxidant, antitumor activities and pH-sensitive drug release. Carbohydrate Polymers, 273, 118623.
- Mohammadi, G., Mirzaeei, S., Taghe, S., & Mohammadi, P. (2019). Preparation and evaluation of Eudragit® L100 nanoparticles loaded impregnated with KT tromethamine loaded PVA -HEC insertions for ophthalmic drug delivery. Advanced Pharmaceutical Bulletin, 9, 593–600.
- Mora-Huertas, C. E., Fessi, H., & Elaissari, A. (2010). Polymer-based nanocapsules for drug delivery. International Journal of Pharmaceutics, 385, 113–142.
- Ovcaricek, T., Frkovic, S. G., Matos, E., Mozina, B., & Borstnar, S. (2011). Triple negative breast cancer - prognostic factors and survival. Radiology and Oncology, 45, 46–52.
- Peddi, P. F. (2022). Triple negative breast cancer: Any closer to cracking the code? Current Opinion in Obstetrics and Gynecology, 34, 52–55.
- Pereira, E. J., Burns, J. S., Lee, C. Y., Marohl, T., Calderon, D., Wang, L., Atkins, K. A., Wang, C. C., & Janes, K. A. (2020). Sporadic activation of an oxidative stress-dependent NRF2-p53 signaling network in breast epithelial spheroids and premalignancies. Science Signaling, 13, eaba4200.
- Pohl, S. G., Brook, N., Agostino, M., Arfuso, F., Kumar, A. P., & Dharmarajan, A. (2017). Wnt signaling in triple-negative breast cancer. Oncogene, 6, e310.
- Qiu, S., Sun, H., Zhang, A. H., Xu, H. Y., Yan, G. L., Han, Y., & Wang, X. J. (2014). Natural alkaloids: Basic aspects, biological roles, and future perspectives, Chin. Journal of Natural Medicines, 12, 401–406.
- Reya, T., & Clevers, H. (2005). Wnt signalling in stem cells and cancer. Nature, 434, 843–850.
- Riley, R. S., & Day, E. S. (2017). Frizzled7 antibody-functionalized nanoshells enable multivalent binding for Wnt signaling inhibition in triple negative breast cancer cells. Small, 13, 1700544.
- Takooree, H., Aumeeruddy, M. Z., Rengasamy, K. R. R., Venugopala, K. N., Jeewon, R., Zengin, G., & Mahomoodally, M. F. (2019). A systematic review on black pepper (Piper nigrum L.): From folk uses to pharmacological applications. Critical Reviews in Food Science and Nutrition, 59, S210–S243.
- Wang, Y., Wang, L., Tan, J., Li, R., Jiang, Z. T., & Tang, S. H. (2021). Comparative analysis of intracellular and in vitro antioxidant activities of essential oil from white and black pepper (Piper nigrum L.). Frontiers in Pharmacology, 12, 680754.
- Xu, M., Almasi, S., Yang, Y., Yan, C., Sterea, A. M., Rizvi Syeda, A. K., Shen, B., Richard Derek, C., Huang, P., Gujar, S., Wang, J., Zong, W. X., Trebak, M., El Hiani, Y., & Dong, X. P. (2019). The lysosomal TRPML1 channel regulates triple negative breast cancer development by promoting mTORC1 and purinergic signaling pathways. Cell Calcium, 79, 80–88.
- Yang, J., Hong, S., Zhang, X., Liu, J., Wang, Y., Wang, Z., Gao, L., & Hong, L. (2021). Tumor immune microenvironment related gene-based model to predict prognosis and response to compounds in ovarian cancer. Frontiers in Oncology, 11, 807410.
- Yang, M., Li, J., Gu, P., & Fan, X. (2021). The application of nanoparticles in cancer immunotherapy: Targeting tumor microenvironment. Bioactive Materials, 6, 1973–1987.
- Yin, X., Lu, Y., Zou, M., Wang, L., Zhou, X., Zhang, Y., & Su, M. (2021). Synthesis and characterization of salinomycin-loaded high-density lipoprotein and its effects on cervical cancer cells and cervical cancer stem cells. International Journal of Nanomedicine, 16, 6367–6382.
- Yu, X., Lin, H., Wang, Y., Lv, W., Zhang, S., Qian, Y., Deng, X., Feng, N., Yu, H., & Qian, B. (2018). d-limonene exhibits antitumor activity by inducing autophagy and apoptosis in lung cancer. Oncotargets and Therapy, 11, 1833–1847.
- Zhang, C., Zhao, J., Famous, E., Pan, S., Peng, X., & Tian, J. (2021). Antioxidant, hepatoprotective and antifungal activities of black pepper (Piper nigrum L.) essential oil. Food Chemistry, 346, 128845.
- Zhang, J., Ye, K. P., Zhang, X., Pan, D. D., Sun, Y. Y., & Cao, J. X. (2016). Antibacterial activity and mechanism of action of black pepper essential oil on meat-borne Escherichia coli. Frontiers in Microbiology, 7, 2094.
- Zheng, Q., Yao, D., Cai, Y., & Zhou, T. (2020). NLRP3 augmented resistance to gemcitabine in triple-negative breast cancer cells via EMT/IL-1beta/Wnt/beta-catenin signaling pathway. Bioscience Reports, 40, BSR20200730.
