Search JIM Advanced Search

Journal of Integrative Medicine ›› 2019, Vol. 17 ›› Issue (2): 132-140.doi: 10.1016/j.joim.2019.02.001

• Original Experimental Research • Previous Articles     Next Articles

Medicinal properties of Angelica archangelica root extract: Cytotoxicity in breast cancer cells and its protective effects against in vivo tumor development

Carlos R. Oliveira a, b, 1(), Daniel G. Spindola a, b, Daniel M. Garcia a, Adolfo Erustes a, Alexandre Bechara a, Caroline Palmeira-dos-Santos a, Soraya S. Smaili a, Gustavo J.S. Pereira a, André Hinsberger b, Ezequiel P. Viriato c, Maria Cristina Marcucci d, Alexandra C.H.F. Sawaya e, Samantha L. Tomaz f, Elaine G. Rodrigues f, Claudia Bincoletto a,1()   

  1. a Departamento de Farmacologia, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04044-020, Brazil
    b Grupo de Fitocomplexos e Sinalização Celular, Escola de Ciências da Saúde, Universidade Anhembi Morumbi, São Paulo, SP 03164-000, Brazil
    c Faculdade de Ciências Farmacêuticas e Bioquímicas Oswaldo Cruz, São Paulo, SP 01151-000, Brazil
    d Laboratório de Produtos Naturais e Quimiometria, Programa de pós-graduação em Farmácia e Biotecnologia, Universidade Anhanguera de São Paulo, São Paulo, SP 05145-200, Brazil
    e Faculdade de Ciências Farmacêuticas, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-871, Brazil
    f Unidade de Oncologia Experimental, EPM, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP 04023-901, Brazil
  • Received:2018-05-16 Accepted:2018-11-02 Online:2019-03-06 Published:2019-05-18

Although Angelica archangelica is a medicinal and aromatic plant with a long history of use for both medicinal and food purposes, there are no studies regarding the antineoplastic activity of its root. This study aimed to evaluate the cytotoxicity and antitumor effects of the crude extract of A. archangelica root (CEAA) on breast cancer.
The cytotoxicity of CEAA against breast adenocarcinoma cells (4T1 and MCF-7) was evaluated by a 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. Morphological and biochemical changes were detected by Hoechst 33342/propidium iodide (PI) and annexin V/PI staining. Cytosolic calcium mobilization was evaluated in cells staining with FURA-4NW. Immunoblotting was used to determine the effect of CEAA on anti- and pro-apoptotic proteins (Bcl-2 and Bax, respectively). The 4T1 cell-challenged mice were used for in vivo assay.
Using ultra-high-performance liquid chromatography–mass spectrometry analysis, angelicin, a constituent of the roots and leaves of A. archangelica, was found to be the major constituent of the CEAA evaluated in this study (73?μg/mL). The CEAA was cytotoxic for both breast cancer cell lines studied but not for human fibroblasts. Treatment of 4T1 cells with the CEAA increased Bax protein levels accompanied by decreased Bcl-2 expression, in the presence of cleaved caspase-3 and cytosolic calcium mobilization, suggesting mitochondrial involvement in breast cancer cell death induced by the CEAA in this cell line. No changes on the Bcl-2/Bax ratio were observed in CEAA-treated MCF7 cells. Gavage administration of the CEAA (500?mg/kg) to 4T1 cell-challenged mice significantly decreased tumor growth when compared with untreated animals.
Altogether, our data show the antitumor potential of the CEAA against breast cancer cells in vitro and in vivo. Further research is necessary to better elucidate the pharmacological application of the CEAA in breast cancer therapy.

Key words: Angelica archangelica, Umbelliferae, Apoptosis, Cell death, Breast cancer, Angelicin

[1] Cai-lian Fana, Wan-jun Caib, Meng-nan Ye, Miao Chen, Yi Dai. Qili Qiangxin, a compound herbal medicine formula, alleviates hypoxia-reoxygenation-induced apoptotic and autophagic cell death via suppression of ROS/AMPK/mTOR pathway in vitro. Journal of Integrative Medicine, 2022, 20(4): 365-375.
[2] Hong-xiao Li, Ling Shi, Shang-jie Liang Chen-chen Fang, Qian-qian Xu, Ge Lu, Qian Wang, Jie Cheng, Jie Shen, Mei-hong Shen. Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway. Journal of Integrative Medicine, 2022, 20(2): 163-172.
[3] Ofer Baranovitch, Meirav Wolff-Bar, Meora Feinmesser, Chen Sade-Zaltz, Ilan Tsarfaty, Victoria Neiman. Searching for the emotional roots of breast cancer: A cross-disciplinary analysis integrating psychology, Chinese medicine, and oncology biomarkers. Journal of Integrative Medicine, 2022, 20(1): 57-64.
[4] Mohamed S. Othman, Sofian T. Obeidat, Amal H. Al-Bagawi, Mohamed A. Fareid, Alaa Fehaid, Ahmed E. Abdel Moneim. Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent#br#
. Journal of Integrative Medicine, 2022, 20(1): 65-72.
[5] Hyongjun Jeon, Hee-Young Kim, Chang-Hwan Bae, Yukyung Lee, Sungtae Koo, Seungtae Kim. Korean red ginseng decreases 1-methyl-4-phenylpyridinium-induced mitophagy in SH-SY5Y cells. Journal of Integrative Medicine, 2021, 19(6): 537-544.
[6] Porwornwisit Tritripmongkol, Tullayakorn Plengsuriyakarn, Mayuri Tarasuk, Kesara Na-Bangchang. In vitro cytotoxic and toxicological activities of ethanolic extract of Kaempferia galanga Linn. and its active component, ethyl-p-methoxycinnamate, against cholangiocarcinoma. Journal of Integrative Medicine, 2020, 18(4): 326-333.
[7] Varuni Colamba Pathiranage, Ira Thabrew, Sameera R. Samarakoon, Kamani H. Tennekoon, Umapriyatharshini Rajagopalan, Meran K. Ediriweera. Evaluation of anticancer effects of a pharmaceutically viable extract of a traditional polyherbal mixture against non-small-cell lung cancer cells. Journal of Integrative Medicine, 2020, 18(3): 242-252.
[8] Fatemeh Sadat Hasheminas, Seyed Mehdi Hashemi, Azizallah Dehghan, Fariba Sharififar, Mohammad Setayesh, Pegah Sasanpour, Mojtaba Tasbandi, Mahboobeh Raeiszadeh. Effects of a Plantago ovata-based herbal compound in prevention and treatment of oral mucositis in patients with breast cancer receiving chemotherapy: A double-blind, randomized, controlled crossover trial. Journal of Integrative Medicine, 2020, 18(3): 214-221.
[9] Maged Mohamed Maher Abou-Hashem, Dina Mohamed Abo-elmatty, Noha Mostafa Mesbah, Ahmed Mohamed Abd EL-Mawgoud. Induction of sub-G0 arrest and apoptosis by seed extract of Moringa peregrina (Forssk.) Fiori in cervical and prostate cancer cell lines. Journal of Integrative Medicine, 2019, 17(6): 410-422.
[10] Supakanya Kumkarnjana, Rutt Suttisri, Ubonthip Nimmannit, Apirada Sucontphunt, Mattaka Khongkow, Thongchai Koobkokkruad, Nontima Vardhanabhuti. Flavonoids kaempferide and 4,2′-dihydroxy-4′,5′,6′-trimethoxychalcone inhibit mitotic clonal expansion and induce apoptosis during the early phase of adipogenesis in 3T3-L1 cells. Journal of Integrative Medicine, 2019, 17(4): 288-295.
[11] Shriniwas S. Basaiyye, Sanjay Kashyap, Kannan Krishnamurthi, Saravanadevi Sivanesan. Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.). Journal of Integrative Medicine, 2019, 17(3): 221-228.
[12] Bruno José Martins Da Silva, Sandro Wilson Gomes Pereira, Ana Paula Drummond Rodrigues, José Luiz Martins Do Nascimento, Edilene Oliveira Silva. In vitro antileishmanial effects of Physalis angulata root extract on Leishmania infantum. Journal of Integrative Medicine, 2018, 16(6): 404-410.
[13] Eric Wei Chiang Chan, Siu Kuin Wong, Hung Tuck Chan . Casticin from Vitex species: A short review on its anticancer and anti-inflammatory properties. Journal of Integrative Medicine, 2018, 16(3): 147-152.
[14] Lizhou Liu, Simone Petrich, Blair McLaren, Lyndell Kelly, G. David Baxter. An integrative Tai Chi program for patients with breast cancer undergoing cancer therapy: Study protocol for a randomized controlled feasibility study. Journal of Integrative Medicine, 2018, 16(2): 99-105.
[15] Gloria Gronowicz, Eric R. Secor Jr., John R. Flynn, Liisa T. Kuhn. Human biofield therapy does not affect tumor size but modulates immune responses in a mouse model for breast cancer. Journal of Integrative Medicine, 2016, 14(5): 389-399.
Full text



[1] Wei-xiong Liang. Problems-solving strategies in clinical treatment guideline for traditional Chinese medicine and integrative medicine. Journal of Chinese Integrative Medicine, 2008, 6(1): 1-4
[2] Zhao-guo Li. Discussion on English translation of commonly used sentences in traditional Chinese medicine: part one. Journal of Chinese Integrative Medicine, 2008, 6(1): 107-110
[3] Jun Hu, Jian-ping Liu. Non-invasive physical treatments for chronic/recurrent headache. Journal of Chinese Integrative Medicine, 2008, 6(1): 31
[4] Xue-mei Liu, Qi-fu Huang, Yun-ling Zhang, Jin-li Lou, Hong-sheng Liu, Hong Zheng. Effects of Tribulus terrestris L. saponion on apoptosis of cortical neurons induced by hypoxia-reoxygenation in rats. Journal of Chinese Integrative Medicine, 2008, 6(1): 45-50
[5] . Uniform requirements for manuscripts submitted to biomedical journals: Writing and editing for biomedical publication (Chinese version, part two). Journal of Chinese Integrative Medicine, 2010, 8(11): 1001-1005
[6] Daniel Weber, Janelle M Wheat, Geoffrey M Currie. Inflammation and cancer: Tumor initiation, progression and metastasis,and Chinese botanical medicines. Journal of Chinese Integrative Medicine, 2010, 8(11): 1006-1013
[7] Hong Liu , Guo-liang Zhang, Li Shen , Zhen Zeng, Bao-luo Zhou, Cheng-hai Liu, Guang Nie . Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5Nl avian influenza virus. Journal of Chinese Integrative Medicine, 2010, 8(11): 1036-1040
[8] Zhao-guo Li . A discussion of English translation of 1995 and 1997 Chinese National Standards of Traditional Chinese Medical Terminologies for Clinical Diagnosis and Treatment. Journal of Chinese Integrative Medicine, 2010, 8(11): 1090-1096
[9] Rui Jin, Bing Zhang. A complexity analysis of Chinese herbal property theory: the multiple formations of herbal property (Part 1). Journal of Chinese Integrative Medicine, 2012, 10(11): 1198-1205
[10] Hui-min Liu, Xian-bo Wang, Yu-juan Chang, Li-li Gu. Systematic review and meta-analysis of randomized controlled trials of integrative medicine therapy for treatment of chronic severe hepatitis. Journal of Chinese Integrative Medicine, 2012, 10(11): 1211-1228