Hedyotis corymbosa nanoliposomes anticancer activity

Excerpt:


J. Pharm. Pharmacogn. Res., vol. 12, no. 2, pp. 303-322, Mar-Apr 2024. DOI: https://doi.org/10.56499/jppres23.1783_12.2.303 Original Article Anticancer activity of Hedyotis corymbosa nanoliposomes targeting estrogen receptor-alpha in breast cancer cells: In silico and in vitro studies [Actividad anticancerígena de nanoliposomas de Hedyotis corymbosa dirigidos al receptor alfa de estrógeno en células de cáncer de mama: Estudios … Continue reading Hedyotis corymbosa nanoliposomes anticancer activity

J. Pharm. Pharmacogn. Res., vol. 12, no. 2, pp. 303-322, Mar-Apr 2024.

DOI: https://doi.org/10.56499/jppres23.1783_12.2.303

Original Article

Anticancer activity of Hedyotis corymbosa nanoliposomes targeting estrogen receptor-alpha in breast cancer cells: In silico and in vitro studies

[Actividad anticancerígena de nanoliposomas de Hedyotis corymbosa dirigidos al receptor alfa de estrógeno en células de cáncer de mama: Estudios in silico e in vitro]

Sofy Permana1*, Laili Nurzaidah2, Edwin Widodo3, Kenty W. Anita4, Raditya W. Nugraheni5, Yoshiyuki Kawamoto6, Heni Endrawati7, Agustina T. Endharti7,8

1Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Brawijaya, Indonesia.

2Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Brawijaya, Indonesia.

3Department of Physiology, Faculty of Medicine, Universitas Brawijaya, Indonesia.

4Department of Pathology Anatomy, Faculty of Medicine, Universitas Brawijaya, Indonesia.

5Department of Pharmacy, Faculty of Health Sciences, Universitas Muhammadiyah Malang, Indonesia.

6Department of Biomedical Sciences, Graduate School of Life and Health Sciences, Chubu University Japan.

7Department of Parasitology, Faculty of Medicine, Universitas Brawijaya, Indonesia.

8Biomedical Central Laboratory, Faculty of Medicine, Universitas Brawijaya, Indonesia.

*E-mail: sofy-bio@ub.ac.id

Abstract

Context: Breast cancer expresses high levels of the estrogen receptor alpha (ER-α).

Aims: To investigate the potential anticancer activity of nanoliposome Hedyotis corymbosa in breast cancer cells by specifically targeting the ER-α through a combination of in silico and in vitro studies.

Methods: This study used molecular docking to analyze the interaction between ER-α and active compounds from H. corymbosa. In vitro studies, the H. corymbosa extract was converted into nanoliposomes. The nanoliposomes' characteristics were examined, combined with tamoxifen, and applied to breast cancer cell cultures. Viability, proliferation, and ER-α expression were assessed, and statistical analysis was performed (p<0.05).

Results: The findings show that H. corymbosa compounds, especially rutin, inhibit ER -α binding and act as a substrate for P-glycoprotein. Extract H. corymbosa selectively decreases viability in breast cancer cells (T47D) compared to non-cancerous cells (NIH3T3). Combining extracts with tamoxifen at 10 mg/mL enhances treatment efficacy. The combined treatment is effective for up to 72 h, reducing T47D breast cancer cell proliferation. Nanoliposomes derived from extract exhibit favorable characteristics, including a spherical shape, uniform size distribution, and stability. Using these nanoliposomes at 100 μg/mL with tamoxifen significantly reduces ER-α expression (p<0.05) without affecting cell viability.

Conclusions: Compounds from H. corymbosa, especially rutin, inhibit ER-α binding. H. corymbosa nanoliposomes are stable for drug delivery. Combining tamoxifen with nanoliposomes at 100 μg/mL reduces ER-alpha expression. This shows potential for breast cancer treatment, but validation through further research and clinical trials is necessary.

Keywords: breast cancer; estrogen receptor alpha; Hedyotis; liposomes; rutin.

jppres_pdf_free

Resumen

Contexto: El cáncer de mama expresa altos niveles del receptor alfa de estrógenos (ER-α).

Objetivos: Investigar la potencial actividad anticancerígena del nanoliposoma Hedyotis corymbosa en células de cáncer de mama dirigiéndose específicamente al ER-α mediante una combinación de estudios in silico e in vitro.

Métodos: Este estudio utilizó el acoplamiento molecular para analizar la interacción entre el ER-α y los compuestos activos de H. corymbosa. En estudios in vitro, el extracto de H. corymbosa se convirtió en nanoliposomas. Se examinaron las características de los nanoliposomas, se combinaron con tamoxifeno y se aplicaron a cultivos de células de cáncer de mama. Se evaluaron la viabilidad, la proliferación y la expresión de ER-α, y se realizó un análisis estadístico (p<0,05).

Resultados: Los resultados muestran que los compuestos de H. corymbosa, especialmente la rutina, inhiben la unión a ER-α y actúan como sustrato de la glicoproteína P. El extracto H. corymbosa disminuye selectivamente la viabilidad en células de cáncer de mama (T47D) en comparación con células no cancerosas (NIH3T3). La combinación de los extractos con tamoxifeno a 10 mg/mL aumenta la eficacia del tratamiento. El tratamiento combinado es eficaz hasta 72 h, reduciendo la proliferación de células de cáncer de mama T47D. Los nanoliposomas derivados del extracto presentan características favorables, como forma esférica, distribución uniforme del tamaño y estabilidad. El uso de estos nanoliposomas a 100 μg/mL con tamoxifeno reduce significativamente la expresión de ER-α (p<0,05) sin afectar a la viabilidad celular.

Conclusiones: Los compuestos de H. corymbosa, especialmente la rutina, inhiben la unión de ER-α. Los nanoliposomas de H. corymbosa son estables para la administración de fármacos. La combinación de tamoxifeno con nanoliposomas a 100 μg/mL reduce la expresión de ER-alfa. Esto demuestra su potencial para el tratamiento del cáncer de mama, pero es necesario validarlo mediante nuevas investigaciones y ensayos clínicos.

Palabras Clave: cáncer de mama; Hedyotis; liposomas; receptor de estrógenos alfa; rutina.

jppres_pdf_free
 
Citation Format: Permana S, Nurzaidah L, Widodo E, Anita KW, Nugraheni RW, Kawamoto Y, Endrawati H, Endharti AT (2024) Anticancer activity of Hedyotis corymbosa nanoliposomes targeting estrogen receptor-alpha in breast cancer cells: In silico and in vitro studies. J Pharm Pharmacogn Res 12(2): 303–322. https://doi.org/10.56499/jppres23.1783_12.2.303
References

Akbari B, Tavandashti MP, Zandrahimi M (2011) Particle size characterization of nanoparticles – A practical approach. Iran J Mater Sci Eng 8(2): 48-56.

Arao Y, Korach KS (2019) Transactivation function-1-mediated partial agonist activity of selective estrogen receptor modulator requires homo-dimerization of the estrogen receptor α ligand binding domain. Int J Mol Scie 20(15): 3718. https://doi.org/10.3390/ijms20153718

Arnott JA, Planey SL (2012) The influence of lipophilicity in drug discovery and design. Expert Opin Drug Discov 7(10): 863–875. https://doi.org/10.1517/17460441.2012.714363

Artanti N, Hanafi M, Andriyani R, Saraswaty V, Zalinar Udin L, D Lotulung P, Ichi Fujita K, Usuki Y (2015) Isolation of an anti-cancer asperuloside from Hedyotis corymbosa L. J Trop Life Scie 5(2): 88–91. https://doi.org/10.11594/jtls.05.02.06

Bafna D, Ban F, Rennie PS, Singh K, Cherkasov A (2020) Computer-aided ligand discovery for estrogen receptor alpha. Int J Mol Scie 21(12): 4193. https://doi.org/10.3390/ijms21124193

Bahmani A, Saaidpour S, Rostami A (2017) A simple, robust and efficient computational method for n-octanol/water partition coefficients of substituted aromatic drugs. Sci Rep 7(1): 5760. https://doi.org/10.1038/s41598-017-05964-z

Benet LZ, Hosey CM, Ursu O, Oprea TI (2016) BDDCS, the Rule of 5 and drugability. Adv Drug Deliv Rev 101: 89–98. https://doi.org/10.1016/j.addr.2016.05.007

Chen R, He J, Tong X, Tang L, Liu M (2016) The Hedyotis diffusa Willd. (Rubiaceae): A review on phytochemistry, pharmacology, quality control and pharmacokinetics. Molecules 21(6): 710. https://doi.org/10.3390/molecules21060710

Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y (2012) admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 52(11): 3099–3105. https://doi.org/10.1021/ci300367a

Chothiphirat A, Nittayaboon K, Kanokwiroon K, Srisawat T, Navakanitworakul R (2019) Anticancer potential of fruit extracts from Vatica diospyroides Symington yype SS and their effect on program cell death of cervical cancer cell lines. Scie World J 2019: 5491904 . https://doi.org/10.1155/2019/5491904

Chotphruethipong L, Battino M, Benjakul S (2020) Effect of stabilizing agents on characteristics, antioxidant activities and stability of liposome loaded with hydrolyzed collagen from defatted Asian sea bass skin. Food Chem 328: 127127. https://doi.org/10.1016/j.foodchem.2020.127127

Daina A, Michielin O, Zoete V (2017) SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 7(1): 42717. https://doi.org/10.1038/srep42717

Deng H, Zhang XT, Wang ML, Zheng HY, Liu LJ, Wang ZY (2014) ER-α36-mediated rapid estrogen signaling positively regulates ER-positive breast cancer stem/progenitor cells. PLoS One 9(2): e88034. https://doi.org/10.1371/journal.pone.0088034

Fatunde OA, Brown S-A (2020) The role of CYP450 drug metabolism in precision cardio-oncology. Int J Mol Sci 21(2): 604. https://doi.org/10.3390/ijms21020604

Feng A, Yang S, Sun Y, Zhang L, Bo F, Li L (2020) Development and evaluation of oleanolic acid dosage forms and its derivatives. BioMed Res Int 2020: 1308749. https://doi.org/10.1155/2020/1308749

Foo BJ-A, Eu JQ, Hirpara JL, Pervaiz S (2021) Interplay between mitochondrial metabolism and cellular redox state dictates cancer cell survival. Oxid Med Cell Longev 2021: 1341604. https://doi.org/10.1155/2021/1341604

Fu Z, Lin Z, Yang M, Li C (2022) Cardiac toxicity from adjuvant targeting treatment for breast cancer post-surgery. Front Oncol 12: 706861. https://doi.org/10.3389/fonc.2022.706861

Gibellini L, Pinti M, Nasi M, De Biasi S, Roat E, Bertoncelli L, Cossarizza A (2010) Interfering with ROS metabolism in cancer cells: The potential role of quercetin. Cancers 2(2): 1288–1311. https://doi.org/10.3390/cancers2021288

Globocan (2020) Global Cancer Observatory: Populations 360 Indonesia Fact Sheets. https://gco.iarc.fr/today/data/factsheets/populations/360-indonesia-fact-sheets.pdf [Accessed 23 January 2023].

Haidinger R, Bauerfeind I (2019) Long-term side effects of adjuvant therapy in primary breast cancer patients: Results of a web-based survey. Breast Care 14(2): 111–116. https://doi.org/10.1159/000497233

Harbeck N, Penault-Llorca F, Cortes J, Gnant M, Houssami N, Poortmans P, Ruddy K, Tsang J, Cardoso F (2019) Breast cancer. Nat Rev Dis Primers 5(1): 66. https://doi.org/1038/s41572-019-0111-2

Honary S, Zahir F (2013) Effect of Zeta potential on the properties of nano-drug delivery systems - A review (Part 2). Trop J Pharm Res 12(2): 265–273. http://dx.doi.org/10.4314/tjpr.v12i2.20

Ji D, Xu M, Udenigwe CC, Agyei D (2020) Physicochemical characterisation, molecular docking, and drug-likeness evaluation of hypotensive peptides encrypted in flaxseed proteome. Curr Res Food Sci 3: 41–50. https://doi.org/10.1016/j.crfs.2020.03.001

Khosrow-Khavar F, Filion KB, Al-Qurashi S, Torabi N, Bouganim N, Suissa S, Azoulay L (2017) Cardiotoxicity of aromatase inhibitors and tamoxifen in postmenopausal women with breast cancer: A systematic review and meta-analysis of randomized controlled trials. Ann Oncol 28(3): 487–496. https://doi.org/10.1093/annonc/mdw673

Larsson P, Engqvist H, Biermann J, Werner Rönnerman E, Forssell-Aronsson E, Kovács A, Karlsson P, Helou K, Parris TZ (2020) Optimization of cell viability assays to improve replicability and reproducibility of cancer drug sensitivity screens. Sci Rep 10(1): 5798. https://doi.org/10.1038/s41598-020-62848-5

Li Y, Zhang H, Jiang T, Li P (2022) Role of estrogen receptor-positive/negative ratios in regulating breast cancer. Evid Based Complement Alternat Med 2022: 7833389. https://doi.org/10.1155/2022/7833389

Lin H-J, Tseng C-P, Lin C-F, Liao M-H, Chen C-M, Kao S-T, Cheng J-C (2011) A Chinese herbal decoction, modified Yi Guan Jian, induces apoptosis in hepatic stellate cells through an ROS-mediated mitochondrial/caspase pathway. Evid Based Complement Alternat Med 2011: 459531. https://doi.org/10.1155/2011/459531

Matsson P, Kihlberg J (2017) How big is too big for cell permeability? J Med Chem 60(5): 1662–1664. https://doi.org/10.1021/acs.jmedchem.7b00237

Mohana S, Ganesan M, Agilan B, Karthikeyan R, Srithar G, Beaulah Mary R, Ananthakrishnan D, Velmurugan D, Rajendra Prasad N, Ambudkar SV (2016) Screening dietary flavonoids for the reversal of P-glycoprotein-mediated multidrug resistance in cancer. Mol BioSyst 12(8): 2458–2470. https://doi.org/10.1039/c6mb00187d

Nafisah W, Wahyuningsih N, Maulana MF, Azmi SZK, Rifa’i M, Widodo N, Djati MS (2023) Cyperus rotundus L. rhizome extract modulates immune system and induces apoptotic in 4T1-tumor bearing mice. J Pharm Pharmacogn Res 11(4): 674–682. https://doi.org/10.56499/jppres23.1604_11.4.674

Novitasari D, Handayani S, Jenie RI (2018) Ethanolic extract of Hedyotis corymbosa L. inhibits migration and MMP-9 activity on metastatic breast cancer cells. Indones J Cancer Chemoprevent 9(1): 16. http://dx.doi.org/10.14499/indonesianjcanchemoprev9iss1pp16-22

Pace CN, Fu H, Lee Fryar K, Landua J, Trevino SR, Schell D, Thurlkill RL, Imura S, Scholtz JM, Gajiwala K, Sevcik J, Urbanikova L, Myers JK, Takano K, Hebert EJ, Shirley BA, Grimsley GR (2014) Contribution of hydrogen bonds to protein stability. Protein Sci 23(5): 652–661. https://doi.org/10.1002/pro.2449

Pantsar T, Poso A (2018) Binding affinity via docking: fact and fiction. Molecules 23(8): 1899. https://doi.org/10.3390/molecules23081899

Pattni BS, Jhaveri A, Dutta I, Baleja JD, Degterev A, Torchilin V (2017) Targeting energy metabolism of cancer cells: Combined administration of NCL-240 and 2-DG. Int J Pharm 532(1): 149–156. https://doi.org/10.1016/j.ijpharm.2017.08.095

Phatak RS (2015) Phytochemistry, pharmacological activities and intellectual property landscape of Gardenia jasminoides Ellis: A review. Phcog J 7(5): 254–265. https://doi.org/10.5530/pj.2015.5.1

Prasad S, Yadav VR, Kannappan R, Aggarwal BB (2011) Ursolic acid, a pentacyclin triterpene, potentiates TRAIL-induced apoptosis through p53-independent up-regulation of death receptors. J Biol Chem 286(7): 5546–5557. https://doi.org/10.1074/jbc.M110.183699

Rachmawati H, Winarsih S, Prawiro SR, Barlianto W, Santoso S, Djunaedi D, Endharti AT, Sardjono TW, Khotimah H, Prihanti GS, Nugraheni RW, Sumadi FAN, Yusuf H (2020) AdhO36 liposomes from Salmonella typhi in combination with β-glucan immuno-adjuvant from Candida albicans cell wall as oral vaccine against typhoid fever in mice model. Open Access Maced J Med Sci 8(A): 441–448. https://doi.org/10.3889/oamjms.2020.4422

Rollando R (2018) Hedyotis corymbosa L. and Sterculia quadrifida R.Br ethanolic extract enhances cisplatin’s cytotoxicity on t47d breast cancer cells through cell cycle modulation. J Pure App Chem Res 7(2): 159–171. http://dx.doi.org/10.22159/ajpcr.2018.v11i7.25607

Rusidzé M, Adlanmérini M, Chantalat E, Raymond-Letron I, Cayre S, Arnal J-F, Deugnier M-A, Lenfant F (2021) Estrogen receptor-α signaling in post-natal mammary development and breast cancers. Cell Mol Life Sci 78(15): 5681–5705. https://doi.org/10.1007/s00018-021-03860-4

Sandhiya V, Ubaidulla U (2020) A review on herbal drug loaded into pharmaceutical carrier techniques and its evaluation process. Futur J Pharm Sci 6(1): 51. https://doi.org/10.1186/s43094-020-00050-0

Satari A, Ghasemi S, Habtemariam S, Asgharian S, Lorigooini Z (2021) Rutin: A flavonoid as an effective sensitizer for anticancer therapy; insights into multifaceted mechanisms and applicability for combination therapy. Evid Based Complement Alternat Med 2021: 9913179. https://doi.org/10.1155/2021/9913179

Seetharaman M, Krishnan G, Schneider RH (2021) The future of medicine: Frontiers in integrative health and medicine. Medicina 57(12): 1303. https://doi.org/10.3390/medicina57121303

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA A Cancer J Clinicians 71(3): 209–249. https://doi.org/10.3322/caac.21660

The Ministry of Health of the Republic of Indonesia (2022) Kanker Payudara Paling Banyak di Indonesia, Kemenkes Targetkan Pemerataan Layanan Kesehatan. https://www.kemkes.go.id/id/rilis-kesehatan/kanker-payudaya-paling-banyak-di-indonesia-kemenkes-targetkan-pemerataan-layanan-kesehatan [Accessed 23 January 2023].

Waghdhare SS (2021) Phytochemical and pharmacological profile of Oldenandia corymbosa plant: A review. Int Res J Modern Eng Technol Sci 3(12): 995–1004.

Wang Z, Chen Y, Liang H, Bender A, Glen RC, Yan A (2011) P-glycoprotein substrate models using support vector machines based on a comprehensive data set. J Chem Inf Model 51(6): 1447–1456. https://doi.org/10.1021/ci2001583

Yaşar P, Ayaz G, User SD, Güpür G, Muyan M (2017) Molecular mechanism of estrogen–estrogen receptor signaling. Reprod Med Biol 16(1): 4–20. https://doi.org/10.1002/rmb2.12006

Youssef SSM, Ibrahim NK, El-Sonbaty SM, El-Din Ezz MK (2022) Rutin suppresses DMBA carcinogenesis in the breast through modulating IL-6/NF-κB, SRC1/HSP90 and ER-α. Nat Prod Comm 17(9): 1–11. https://doi.org/10.1177/1934578X221118213

Yusuf H, Nugraheni R, Setyawan D (2019) Effect of cellulose derivative matrix and oligosaccharide on the solid state and physical characteristics of dimethyldioctadecylammonium-liposomes for vaccine. Res Pharma Sci 14(1): 1–11. https://doi.org/10.4103/1735-5362.251847

Zhang L, Zhang J, Qi B, Jiang G, Liu J, Zhang P, Ma Y, Li W (2016) The anti-tumor effect and bioactive phytochemicals of Hedyotis diffusa Willd on ovarian cancer cells. J Ethnopharmacol 192: 132–139. https://doi.org/10.1016/j.jep.2016.07.027

Zheng J (2012) Energy metabolism of cancer: Glycolysis versus oxidative phosphorylation (Review). Oncol Lett 4(6): 1151–1157. https://doi.org/10.3892/ol.2012.928

Zhu Y, Liu Y, Zhang C, Chu J, Wu Y, Li Y, Liu J, Li Q, Li S, Shi Q, Jin L, Zhao J, Yin D, Efroni S, Su F, Yao H, Song E, Liu Q (2018) Tamoxifen-resistant breast cancer cells are resistant to DNA-damaging chemotherapy because of upregulated BARD1 and BRCA1. Nat Commun 9(1): 1595. https://doi.org/10.1038/s41467-018-03951-0

© 2024 Journal of Pharmacy & Pharmacognosy Research

Anti-dormant mycobacterial of marine-derived fungi
J. Pharm. Pharmacogn. Res., vol. 13, no. 1, pp. 16-26, Jan-Feb 2025. DOI: https://doi.org/10.56499/jppres24.1953_13.1.16 Original Article Activity of ethyl acetate extracts of marine-derived fungi against active and hypoxia-induced dormant Mycobacterium [Actividad de extractos de acetato de etilo de hongos de origen marino contra Mycobacterium latente activa e inducida por hipoxia] Muhammad Azhari1, Atik Pereztia Litanjuasari1, … Continue reading Anti-dormant mycobacterial of marine-derived fungi
Rift Valley fever virus RdRp inhibition by RNA polymerase inhibitors
J. Pharm. Pharmacogn. Res., vol. 13, no. 1, pp. 1-15, Jan-Feb 2025. DOI: https://doi.org/10.56499/jppres24.1967_13.1.1 Original Article In silico study of RNA polymerase inhibitor drugs for Rift Valley fever virus using RdRp protein as the target [Estudio in silico de fármacos inhibidores de la ARN polimerasa para el virus de la fiebre del valle del Rift … Continue reading Rift Valley fever virus RdRp inhibition by RNA polymerase inhibitors
Probable interaction between levothyroxine and Thymus vulgaris
J. Pharm. Pharmacogn. Res., vol. 12, no. 6, pp. 1196-1198, Nov-Dec 2024. DOI: https://doi.org/10.56499/jppres24.2008_12.6.1196 Case Report Probable interaction between levothyroxine sodium and thyme (Thymus vulgaris), about a case report [Interacción probable entre levotiroxina sódica y tomillo (Thymus vulgaris), sobre un reporte de caso] Nassima Elyebdri1,2*, Sihem Baba Ahmed1, Nessrine Abourejal1, Lotfi Loudjedi3, Assia Bououden3, Nour … Continue reading Probable interaction between levothyroxine and Thymus vulgaris

© 2013-2020 by the authors; licensee JPPRes, Antofagasta, Chile. This journal is an open-access journal distributed under the terms and conditions of the Creative Commons Attribution license-Non Commercial 4.0 international. The content on this site is intended for health professionals. If you are not a health professional, please talk to your doctor about any doubts or concerns regarding your health

Made with ♥ by AVAGAX Studio