白藜芦醇对乳腺癌分子机制的研究进展
Research Progress on the Molecular Mechanisms of Resveratrol in Breast Cancer
DOI: 10.12677/wjcr.2024.144023, PDF,    科研立项经费支持
作者: 李 平*, 邹 青, 吕 圆, 杜振芳#:湖南环境生物职业技术学院医药技术学院,湖南 衡阳;李景兴:衡阳市中心医院儿童康复科,湖南 衡阳;徐克前:中南大学湘雅医学院,湖南 长沙
关键词: 白藜芦醇乳腺癌分子机制耐药性Resveratrol Breast Cancer Molecular Mechanisms Drug Resistance
摘要: 白藜芦醇(Resveratrol)是一种天然存在于葡萄、浆果和花生中的多酚化合物,因其显著的抗氧化、抗炎和抗癌特性,近年来在乳腺癌研究中备受关注。文章综述了白藜芦醇在乳腺癌细胞中的分子机制及其在抗肿瘤过程中的作用。白藜芦醇通过靶向多种信号分子,抑制乳腺癌细胞的增殖,诱导细胞凋亡和自噬,抑制细胞迁移和侵袭,并重组细胞代谢。此外,白藜芦醇与化疗和放疗药物具有协同作用的潜力。尽管临床前研究结果令人鼓舞,但白藜芦醇的生物利用度和稳定性问题仍需解决。未来的研究应聚焦于优化白藜芦醇的递送系统,深入揭示其分子作用机制,并评估其长期使用的安全性和有效性,为乳腺癌患者提供更有效的治疗选择。
Abstract: Resveratrol, a polyphenolic compound naturally found in grapes, berries, and peanuts, has attracted significant attention in recent years due to its potent antioxidant, anti-inflammatory, and anti-cancer properties. This review summarizes the molecular mechanisms of resveratrol in breast cancer cells and its role in tumor suppression. Resveratrol exerts its effects by targeting multiple signaling molecules, thereby inhibiting the proliferation of breast cancer cells, inducing apoptosis and autophagy, suppressing cell migration and invasion, and reprogramming cellular metabolism. Additionally, resveratrol shows potential synergistic effects when combined with chemotherapeutic and radiotherapeutic agents. Despite promising preclinical results, issues related to the bioavailability and stability of resveratrol remain to be addressed. Future research should focus on optimizing resveratrol delivery systems, deeply elucidating its molecular mechanisms, and evaluating the safety and efficacy of long-term use, with the ultimate goal of providing more effective treatment options for breast cancer patients.
文章引用:李平, 李景兴, 邹青, 吕圆, 徐克前, 杜振芳. 白藜芦醇对乳腺癌分子机制的研究进展[J]. 世界肿瘤研究, 2024, 14(4): 155-165. https://doi.org/10.12677/wjcr.2024.144023

参考文献

[1] Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D.M., Piñeros, M., Znaor, A., et al. (2021) Cancer Statistics for the Year 2020: An Overview. International Journal of Cancer, 149, 778-789. [Google Scholar] [CrossRef] [PubMed]
[2] Waks, A.G. and Winer, E.P. (2019) Breast Cancer Treatment: A Review. JAMA, 321, 288-300. [Google Scholar] [CrossRef] [PubMed]
[3] Wuerstlein, R. and Harbeck, N. (2017) Neoadjuvant Therapy for HER2-Positive Breast Cancer. Reviews on Recent Clinical Trials, 12, 81-92. [Google Scholar] [CrossRef] [PubMed]
[4] Tao, J.J., Visvanathan, K. and Wolff, A.C. (2015) Long Term Side Effects of Adjuvant Chemotherapy in Patients with Early Breast Cancer. The Breast, 24, S149-S153. [Google Scholar] [CrossRef] [PubMed]
[5] Musyuni, P., Bai, J., Sheikh, A., Vasanthan, K.S., Jain, G.K., Abourehab, M.A.S., et al. (2022) Precision Medicine: Ray of Hope in Overcoming Cancer Multidrug Resistance. Drug Resistance Updates, 65, Article ID: 100889. [Google Scholar] [CrossRef] [PubMed]
[6] Zhu, X., Wong, I.L.K., Chan, K., Cui, J., Law, M.C., Chong, T.C., et al. (2019) Triazole Bridged Flavonoid Dimers as Potent, Nontoxic, and Highly Selective Breast Cancer Resistance Protein (BCRP/ABCG2) Inhibitors. Journal of Medicinal Chemistry, 62, 8578-8608. [Google Scholar] [CrossRef] [PubMed]
[7] Dias, D.A., Urban, S. and Roessner, U. (2012) A Historical Overview of Natural Products in Drug Discovery. Metabolites, 2, 303-336. [Google Scholar] [CrossRef] [PubMed]
[8] Xue, Y., Di, J., Luo, Y., Cheng, K., Wei, X. and Shi, Z. (2014) Resveratrol Oligomers for the Prevention and Treatment of Cancers. Oxidative Medicine and Cellular Longevity, 2014, Article ID: 765832. [Google Scholar] [CrossRef] [PubMed]
[9] Galiniak, S., Aebisher, D. and Bartusik-Aebisher, D. (2019) Health Benefits of Resveratrol Administration. Acta Biochimica Polonica, 66, 13-21. [Google Scholar] [CrossRef] [PubMed]
[10] Nawaz, W., Zhou, Z., Deng, S., Ma, X., Ma, X., Li, C., et al. (2017) Therapeutic Versatility of Resveratrol Derivatives. Nutrients, 9, Article No. 1188. [Google Scholar] [CrossRef] [PubMed]
[11] Mrkus, L., Batinić, J., Bjeliš, N. and Jakas, A. (2018) Synthesis and Biological Evaluation of Quercetin and Resveratrol Peptidyl Derivatives as Potential Anticancer and Antioxidant Agents. Amino Acids, 51, 319-329. [Google Scholar] [CrossRef] [PubMed]
[12] Oh, W.Y. and Shahidi, F. (2018) Antioxidant Activity of Resveratrol Ester Derivatives in Food and Biological Model Systems. Food Chemistry, 261, 267-273. [Google Scholar] [CrossRef] [PubMed]
[13] You, S., Qian, J., Sun, C., Zhang, H., Ye, S., Chen, T., et al. (2018) An Aza Resveratrol-Chalcone Derivative 6b Protects Mice against Diabetic Cardiomyopathy by Alleviating Inflammation and Oxidative Stress. Journal of Cellular and Molecular Medicine, 22, 1931-1943. [Google Scholar] [CrossRef] [PubMed]
[14] Tang, Y., Shi, C., Yang, H., Cai, P., Liu, Q., Yang, X., et al. (2019) Synthesis and Evaluation of Isoprenylation-Resveratrol Dimer Derivatives against Alzheimer’s Disease. European Journal of Medicinal Chemistry, 163, 307-319. [Google Scholar] [CrossRef] [PubMed]
[15] Yang, H.J., Ren, Y.J., Du, C., Jin, L., Li, R. and Xie, N. (2018) Synthesis and Anticoagulant Bioactivity of Heterocyclic Derivatives of Resveratrol. Chemistry of Natural Compounds, 54, 864-868. [Google Scholar] [CrossRef
[16] Wu, H., Chen, L., Zhu, F., Han, X., Sun, L. and Chen, K. (2019) The Cytotoxicity Effect of Resveratrol: Cell Cycle Arrest and Induced Apoptosis of Breast Cancer 4T1 Cells. Toxins, 11, Article No. 731. [Google Scholar] [CrossRef] [PubMed]
[17] Zhang, W., Jiang, H., Chen, Y. and Ren, F. (2019) Resveratrol Chemosensitizes Adriamycin-Resistant Breast Cancer Cells by Modulating Mir-122-5p. Journal of Cellular Biochemistry, 120, 16283-16292. [Google Scholar] [CrossRef] [PubMed]
[18] Hsieh, T., Wong, C., John Bennett, D. and Wu, J.M. (2011) Regulation of P53 and Cell Proliferation by Resveratrol and Its Derivatives in Breast Cancer Cells: An in Silico and Biochemical Approach Targeting Integrin Αvβ3. International Journal of Cancer, 129, 2732-2743. [Google Scholar] [CrossRef] [PubMed]
[19] Giménez‐Bastida, J.A., Ávila‐Gálvez, M.Á., Espín, J.C. and González‐Sarrías, A. (2019) Conjugated Physiological Resveratrol Metabolites Induce Senescence in Breast Cancer Cells: Role of p53/p21 and p16/Rb Pathways, and ABC Transporters. Molecular Nutrition & Food Research, 63, Article ID: 1900629. [Google Scholar] [CrossRef] [PubMed]
[20] Bartolacci, C., Andreani, C., Amici, A. and Marchini, C. (2018) Walking a Tightrope: A Perspective of Resveratrol Effects on Breast Cancer. Current Protein & Peptide Science, 19, 311-322. [Google Scholar] [CrossRef] [PubMed]
[21] He, X., Wang, Y., Zhu, J., Orloff, M. and Eng, C. (2011) Resveratrol Enhances the Anti-Tumor Activity of the mTOR Inhibitor Rapamycin in Multiple Breast Cancer Cell Lines Mainly by Suppressing Rapamycin-Induced AKT Signaling. Cancer Letters, 301, 168-176. [Google Scholar] [CrossRef] [PubMed]
[22] Khan, A., Aljarbou, A.N., Aldebasi, Y.H., Faisal, S.M. and Khan, M.A. (2014) Resveratrol Suppresses the Proliferation of Breast Cancer Cells by Inhibiting Fatty Acid Synthase Signaling Pathway. Cancer Epidemiology, 38, 765-772. [Google Scholar] [CrossRef] [PubMed]
[23] Mohapatra, P., Satapathy, S.R., Das, D., Siddharth, S., Choudhuri, T. and Kundu, C.N. (2014) Resveratrol Mediated Cell Death in Cigarette Smoke Transformed Breast Epithelial Cells Is through Induction of p21Waf1/Cip1 and Inhibition of Long Patch Base Excision Repair Pathway. Toxicology and Applied Pharmacology, 275, 221-231. [Google Scholar] [CrossRef] [PubMed]
[24] Zhang, X., Wu, F., Shi, S., Chen, P., Jin, M. and Zheng, N. (2024) Anti-Cancer Activity and Mechanism of Resveratrol against Triple-Negative Breast Cancer. Journal of Biobased Materials and Bioenergy, 18, 863-867. [Google Scholar] [CrossRef
[25] Vergara, D., Valente, C.M., Tinelli, A., Siciliano, C., Lorusso, V., Acierno, R., et al. (2011) Resveratrol Inhibits the Epidermal Growth Factor-Induced Epithelial Mesenchymal Transition in MCF-7 Cells. Cancer Letters, 310, 1-8. [Google Scholar] [CrossRef] [PubMed]
[26] Hu, C., Liu, Y., Teng, M., Jiao, K., Zhen, J., Wu, M., et al. (2019) Resveratrol Inhibits the Proliferation of Estrogen Receptor-Positive Breast Cancer Cells by Suppressing EZH2 through the Modulation of ERK1/2 Signaling. Cell Biology and Toxicology, 35, 445-456. [Google Scholar] [CrossRef] [PubMed]
[27] Vinod, B.S., Nair, H.H., Vijayakurup, V., Shabna, A., Shah, S., Krishna, A., et al. (2015) Resveratrol Chemosensitizes HER-2-Overexpressing Breast Cancer Cells to Docetaxel Chemoresistance by Inhibiting Docetaxel-Mediated Activation of Her-2-Akt Axis. Cell Death Discovery, 1, Article No. 15061. [Google Scholar] [CrossRef] [PubMed]
[28] Pozo‐Guisado, E., Merino, J.M., Mulero‐Navarro, S., Lorenzo‐Benayas, M.J., Centeno, F., Alvarez‐Barrientos, A., et al. (2005) Resveratrol‐Induced Apoptosis in MCF‐7 Human Breast Cancer Cells Involves a Caspase‐Independent Mechanism with Downregulation of Bcl-2 and NF‐κB. International Journal of Cancer, 115, 74-84. [Google Scholar] [CrossRef] [PubMed]
[29] Kohandel, Z., Farkhondeh, T., Aschner, M., Pourbagher-Shahri, A.M. and Samarghandian, S. (2021) STAT3 Pathway as a Molecular Target for Resveratrol in Breast Cancer Treatment. Cancer Cell International, 21, Article No. 468. [Google Scholar] [CrossRef] [PubMed]
[30] Dong, J., Yang, W., Han, J., Cheng, R. and Li, L. (2020) Effects of Notch Signaling Components from Breast Cancer Cells Treated in Culture with Resveratrol. Research in Veterinary Science, 132, 369-378. [Google Scholar] [CrossRef] [PubMed]
[31] Schmidt, B., Ferreira, C., Alves Passos, C.L., Silva, J.L. and Fialho, E. (2020) Resveratrol, Curcumin and Piperine Alter Human Glyoxalase 1 in MCF-7 Breast Cancer Cells. International Journal of Molecular Sciences, 21, Article No. 5244. [Google Scholar] [CrossRef] [PubMed]
[32] Amini, P. (2021) Resveratrol Induces Apoptosis and Attenuates Proliferation of MCF-7 Cells in Combination with Radiation and Hyperthermia. Current Molecular Medicine, 21, 142-150. [Google Scholar] [CrossRef
[33] Liang, Z., Wan, Y., Zhu, D., Wang, M., Jiang, H., Huang, D., et al. (2021) Resveratrol Mediates the Apoptosis of Triple Negative Breast Cancer Cells by Reducing POLD1 Expression. Frontiers in Oncology, 11, Article ID: 569295. [Google Scholar] [CrossRef] [PubMed]
[34] Alkhalaf, M., El-Mowafy, A., Renno, W., Rachid, O., Ali, A. and Al-Attyiah, R. (2008) Resveratrol-Induced Apoptosis in Human Breast Cancer Cells Is Mediated Primarily through the Caspase-3-Dependent Pathway. Archives of Medical Research, 39, 162-168. [Google Scholar] [CrossRef] [PubMed]
[35] Mirzapur, P., Khazaei, M.R., Moradi, M.T. and Khazaei, M. (2018) Apoptosis Induction in Human Breast Cancer Cell Lines by Synergic Effect of Raloxifene and Resveratrol through Increasing Proapoptotic Genes. Life Sciences, 205, 45-53. [Google Scholar] [CrossRef] [PubMed]
[36] Ferraz da Costa, D.C., Campos, N.P.C., Santos, R.A., Guedes-da-Silva, F.H., Martins-Dinis, M.M.D.C., Zanphorlin, L., et al. (2018) Resveratrol Prevents P53 Aggregation in Vitro and in Breast Cancer Cells. Oncotarget, 9, 29112-29122. [Google Scholar] [CrossRef] [PubMed]
[37] Costa, P.S.d., Ramos, P.S., Ferreira, C., Silva, J.L., El-Bacha, T. and Fialho, E. (2021) Pro-Oxidant Effect of Resveratrol on Human Breast Cancer MCF-7 Cells Is Associated with CK2 Inhibition. Nutrition and Cancer, 74, 2142-2151. [Google Scholar] [CrossRef] [PubMed]
[38] Cheng, T., Wang, C., Lu, Q., Cao, Y., Yu, W., Li, W., et al. (2022) Metformin Inhibits the Tumor-Promoting Effect of Low-Dose Resveratrol, and Enhances the Anti-Tumor Activity of High-Dose Resveratrol by Increasing Its Reducibility in Triple Negative Breast Cancer. Free Radical Biology and Medicine, 180, 108-120. [Google Scholar] [CrossRef] [PubMed]
[39] Kotha, A., Sekharam, M., Cilenti, L., Siddiquee, K., Khaled, A., Zervos, A.S., et al. (2006) Resveratrol Inhibits Src and Stat3 Signaling and Induces the Apoptosis of Malignant Cells Containing Activated Stat3 Protein. Molecular Cancer Therapeutics, 5, 621-629. [Google Scholar] [CrossRef] [PubMed]
[40] Singh, S.S., Vats, S., Chia, A.Y., Tan, T.Z., Deng, S., Ong, M.S., et al. (2017) Dual Role of Autophagy in Hallmarks of Cancer. Oncogene, 37, 1142-1158. [Google Scholar] [CrossRef] [PubMed]
[41] Eskelinen, E. (2011) The Dual Role of Autophagy in Cancer. Current Opinion in Pharmacology, 11, 294-300. [Google Scholar] [CrossRef] [PubMed]
[42] Wang, J., Huang, P., Pan, X., Xia, C., Zhang, H., Zhao, H., et al. (2022) Resveratrol Reverses TGF‐β1‐Mediated Invasion and Metastasis of Breast Cancer Cells via the SIRT3/AMPK/Autophagy Signal Axis. Phytotherapy Research, 37, 211-230. [Google Scholar] [CrossRef] [PubMed]
[43] Pai Bellare, G. and Sankar Patro, B. (2022) Resveratrol Sensitizes Breast Cancer to PARP Inhibitor, Talazoparib through Dual Inhibition of AKT and Autophagy Flux. Biochemical Pharmacology, 199, Article ID: 115024. [Google Scholar] [CrossRef] [PubMed]
[44] Fatehi, R., Rashedinia, M., Akbarizadeh, A.R., Zamani, M. and Firouzabadi, N. (2023) Metformin Enhances Anti-Cancer Properties of Resveratrol in MCF-7 Breast Cancer Cells via Induction of Apoptosis, Autophagy and Alteration in Cell Cycle Distribution. Biochemical and Biophysical Research Communications, 644, 130-139. [Google Scholar] [CrossRef] [PubMed]
[45] Zhang, J., Tian, X. and Xing, J. (2016) Signal Transduction Pathways of EMT Induced by TGF-β, SHH, and WNT and Their Crosstalks. Journal of Clinical Medicine, 5, Article No. 41. [Google Scholar] [CrossRef] [PubMed]
[46] Sun, Y., Zhou, Q., Lu, Y., Zhang, H., Chen, Q., Zhao, M., et al. (2019) Resveratrol Inhibits the Migration and Metastasis of MDA-MB-231 Human Breast Cancer by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition. Molecules, 24, Article No. 1131. [Google Scholar] [CrossRef] [PubMed]
[47] Yar Saglam, A.S., Kayhan, H., Alp, E. and Onen, H.I. (2021) Resveratrol Enhances the Sensitivity of FL118 in Triple-Negative Breast Cancer Cell Lines via Suppressing Epithelial to Mesenchymal Transition. Molecular Biology Reports, 48, 475-489. [Google Scholar] [CrossRef] [PubMed]
[48] Tang, F., Su, Y., Chen, N., Hsieh, H. and Chen, K. (2008) Resveratrol Inhibits Migration and Invasion of Human Breast‐cancer Cells. Molecular Nutrition & Food Research, 52, 683-691. [Google Scholar] [CrossRef] [PubMed]
[49] Tsai, J., Hsu, L., Lin, C., Hong, H., Pan, M., Way, T., et al. (2013) 3,5,4’-Trimethoxystilbene, a Natural Methoxylated Analog of Resveratrol, Inhibits Breast Cancer Cell Invasiveness by Downregulation of PI3K/Akt and Wnt/β-Catenin Signaling Cascades and Reversal of Epithelial-Mesenchymal Transition. Toxicology and Applied Pharmacology, 272, 746-756. [Google Scholar] [CrossRef] [PubMed]
[50] Lacerda-Abreu, M.A., Russo-Abrahão, T. and Meyer-Fernandes, J.R. (2021) Resveratrol Is an Inhibitor of Sodium-Dependent Inorganic Phosphate Transport in Triple-Negative MDA-MB-231 Breast Cancer Cells. Cell Biology International, 45, 1768-1775. [Google Scholar] [CrossRef] [PubMed]
[51] Gomez, L.S., Zancan, P., Marcondes, M.C., Ramos-Santos, L., Meyer-Fernandes, J.R., Sola-Penna, M., et al. (2013) Resveratrol Decreases Breast Cancer Cell Viability and Glucose Metabolism by Inhibiting 6-Phosphofructo-1-Kinase. Biochimie, 95, 1336-1343. [Google Scholar] [CrossRef] [PubMed]
[52] Gao, Y., Wang, Y., Wang, B., et al. (2024) Mechanism of Action of Resveratrol Affecting the Biological Function of Breast Cancer through the Glycolytic Pathway.
[53] Gomes, L., Viana, L., Silva, J.L., Mermelstein, C., Atella, G. and Fialho, E. (2020) Resveratrol Modifies Lipid Composition of Two Cancer Cell Lines. BioMed Research International, 2020, Article ID: 5393041. [Google Scholar] [CrossRef] [PubMed]
[54] Yang, M., Sun, Y., Zhou, W., Xie, X., Zhou, Q., Lu, Y., et al. (2021) Resveratrol Enhances Inhibition Effects of Cisplatin on Cell Migration and Invasion and Tumor Growth in Breast Cancer MDA-MB-231 Cell Models in Vivo and in Vitro. Molecules, 26, Article No. 2204. [Google Scholar] [CrossRef] [PubMed]
[55] Vargas, J.E., Puga, R., Lenz, G., Trindade, C. and Filippi-Chiela, E. (2020) Cellular Mechanisms Triggered by the Cotreatment of Resveratrol and Doxorubicin in Breast Cancer: A Translational in Vitro-in Silico Model. Oxidative Medicine and Cellular Longevity, 2020, Article ID: 5432651. [Google Scholar] [CrossRef] [PubMed]
[56] Al-jubori, A.A., Sulaiman, G.M., Tawfeeq, A.T., Mohammed, H.A., Khan, R.A. and Mohammed, S.A.A. (2021) Layer-by-Layer Nanoparticles of Tamoxifen and Resveratrol for Dual Drug Delivery System and Potential Triple-Negative Breast Cancer Treatment. Pharmaceutics, 13, Article No. 1098. [Google Scholar] [CrossRef] [PubMed]
[57] da Costa Araldi, I.C., Bordin, F.P.R., Cadoná, F.C., Barbisan, F., Azzolin, V.F., Teixeira, C.F., et al. (2018) The in Vitro Radiosensitizer Potential of Resveratrol on MCF-7 Breast Cancer Cells. Chemico-Biological Interactions, 282, 85-92. [Google Scholar] [CrossRef] [PubMed]
[58] Mondal, A. and Bennett, L.L. (2016) Resveratrol Enhances the Efficacy of Sorafenib Mediated Apoptosis in Human Breast Cancer MCF7 Cells through ROS, Cell Cycle Inhibition, Caspase 3 and PARP Cleavage. Biomedicine & Pharmacotherapy, 84, 1906-1914. [Google Scholar] [CrossRef] [PubMed]
[59] Gao, Y. and Tollefsbol, T.O. (2018) Combinational Proanthocyanidins and Resveratrol Synergistically Inhibit Human Breast Cancer Cells and Impact Epigenetic-Mediating Machinery. International Journal of Molecular Sciences, 19, Article No. 2204. [Google Scholar] [CrossRef] [PubMed]
[60] Deus, C.M., Serafim, T.L., Magalhães-Novais, S., Vilaça, A., Moreira, A.C., Sardão, V.A., et al. (2016) Sirtuin 1-Dependent Resveratrol Cytotoxicity and Pro-Differentiation Activity on Breast Cancer Cells. Archives of Toxicology, 91, 1261-1278. [Google Scholar] [CrossRef] [PubMed]
[61] Suh, J., Kim, D. and Surh, Y. (2018) Resveratrol Suppresses Migration, Invasion and Stemness of Human Breast Cancer Cells by Interfering with Tumor-Stromal Crosstalk. Archives of Biochemistry and Biophysics, 643, 62-71. [Google Scholar] [CrossRef] [PubMed]
[62] Kurzava Kendall, L., Ma, Y., Yang, T., Lubecka, K. and Stefanska, B. (2024) Epigenetic Effects of Resveratrol on Oncogenic Signaling in Breast Cancer. Nutrients, 16, Article No. 699. [Google Scholar] [CrossRef] [PubMed]
[63] Han, X., Zhao, N., Zhu, W., Wang, J., Liu, B. and Teng, Y. (2021) Resveratrol Attenuates TNBC Lung Metastasis by Down-Regulating PD-1 Expression on Pulmonary T Cells and Converting Macrophages to M1 Phenotype in a Murine Tumor Model. Cellular Immunology, 368, Article ID: 104423. [Google Scholar] [CrossRef] [PubMed]
[64] Chen, K., Chen, C., Chang, Y. and Chang, M. (2019) Resveratrol Induced Premature Senescence and Inhibited Epithelial-Mesenchymal Transition of Cancer Cells via Induction of Tumor Suppressor Rad9. PLOS ONE, 14, e0219317. [Google Scholar] [CrossRef] [PubMed]
[65] Chen, J., Bai, J. and Yang, K. (2018) Effect of Resveratrol on Doxorubicin Resistance in Breast Neoplasm Cells by Modulating Pi3k/Akt Signaling Pathway. IUBMB Life, 70, 491-500. [Google Scholar] [CrossRef] [PubMed]
[66] Lucas, J., Hsieh, T., Halicka, H.D., Darzynkiewicz, Z. and Wu, J. (2018) Upregulation of PD-L1 Expression by Resveratrol and Piceatannol in Breast and Colorectal Cancer Cells Occurs via HDAC3/p300-Mediated NF-κB Signaling. International Journal of Oncology, 53, 1469-1480. [Google Scholar] [CrossRef] [PubMed]
[67] Cheuk, I.W., Chen, J., Siu, M., Ho, J.C., Lam, S.S., Shin, V.Y., et al. (2021) Resveratrol Enhanced Chemosensitivity by Reversing Macrophage Polarization in Breast Cancer. Clinical and Translational Oncology, 24, 854-863. [Google Scholar] [CrossRef] [PubMed]
[68] Sinha, S., Chatterjee, S., Paul, S., Das, B., Dash, S.R., Das, C., et al. (2022) Olaparib Enhances the Resveratrol-Mediated Apoptosis in Breast Cancer Cells by Inhibiting the Homologous Recombination Repair Pathway. Experimental Cell Research, 420, Article ID: 113338. [Google Scholar] [CrossRef] [PubMed]
[69] Gadag, S., Narayan, R., Nayak, A.S., Catalina Ardila, D., Sant, S., Nayak, Y., et al. (2021) Development and Preclinical Evaluation of Microneedle-Assisted Resveratrol Loaded Nanostructured Lipid Carriers for Localized Delivery to Breast Cancer Therapy. International Journal of Pharmaceutics, 606, Article ID: 120877. [Google Scholar] [CrossRef] [PubMed]
[70] Palminteri, M., Dhakar, N.K., Ferraresi, A., Caldera, F., Vidoni, C., Trotta, F., et al. (2021) Cyclodextrin Nanosponge for the GSH-Mediated Delivery of Resveratrol in Human Cancer Cells. Nanotheranostics, 5, 197-212. [Google Scholar] [CrossRef] [PubMed]
[71] Metawea, O.R.M., Teleb, M., Haiba, N.S., Elzoghby, A.O., Khafaga, A.F., Noreldin, A.E., et al. (2023) Folic Acid-Poly(N-Isopropylacrylamide-Maltodextrin) Nanohydrogels as Novel Thermo-/pH-Responsive Polymer for Resveratrol Breast Cancer Targeted Therapy. European Polymer Journal, 182, Article ID: 111721. [Google Scholar] [CrossRef