Login Register Cart 0
Generic placeholder image

Current Bioactive Compounds

Editor-in-Chief

ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Extracts of Anogeissus leiocarpus and Dillenia indica Inhibit the Growth of MCF-7 Breast Cancer and COV434 Granulosa Tumor Cells by Inducing Apoptosis and Autophagy

Author(s): Temitope O. Lawal*, Nishikant A. Raut, Shitalben R. Patel and Gail B. Mahady

Volume 17, Issue 10, 2021

Published on: 14 February, 2021

Article ID: e190721191390 Pages: 14

DOI: 10.2174/1573407217666210215092955

Price: $65

Abstract

Background: Dillenia indica L. (Dilleniaceae) and Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae) are used in traditional Nigerian medicine to treat various forms of cancer. This study investigated the cytotoxic effects of these plant extracts using COV434 granulosa tumor and MCF-7 breast cancer cells.

Methods: Samples of D. indica and A. leiocarpus were collected in Ibadan, Nigeria, air-dried, and extracted with methanol. Cell viability and cytotoxicity were determined using CellTiter-Glo® 2.0 assay at concentrations from 1 to 100 μg/mL. Caspase activity and apoptosis were determined using Caspase-Glo® 3/7, Caspase-Glo® 8, and ApoTox-Glo™ triplex assays, and qPCR. Autophagy was measured using a Cyto-ID Autophagy Detection Kit.

Results: In COV434, aqueous partitions of A. leiocarpus root (ALR-Aq) and stem bark (ALS-Aq) had IC50s of 23.5 and 26.7 μg/mL, respectively. In MCF-7 cells, the ALR MeOH extract had IC50 of 12.75 μg/mL, while the DIS-Aq had IC50 of 65.28 μg/mL. None of the extracts inhibited the growth of human osteoblasts or rat myoblasts at similar concentrations. Treatment with ALR-Aq and DIS-Aq induced mitochondrial apoptosis in MCF-7 and COV434. Both ALR-Aq and DIS-Aq induced autophagy in COV434 cells, while ALR-Aq induced autophagy in MCF-7 cells. Ellagic acid (IC50 of 3.27μg/mL in COV434 cells) was isolated from ALR-Aq using bioassay-guided fractionation.

Conclusion: DIS-Aq and ALR-Aq induced apoptosis in MCF-7 and COV434 cancer cells. Ellagic acid was isolated as the active constituent. Taken together, these data suggest that both plant extracts have strong anti-proliferative effects, and further investigation for their anticancer effects is warranted.

Keywords: Apoptosis, autophagy, ellagic acid, COV434 granulosa tumor cell, MCF-7 breast cancer cell, Bax, Bcl-2.

Graphical Abstract

[1]
Comşa, Ş.; Cîmpean, A.M.; Raica, M. The story of MCF-7 breast cancer cell line: 40 years of experience in research. Anticancer Res., 2015, 35(6), 3147-3154.
[PMID: 26026074]
[2]
Outwater, E.K.; Wagner, B.J.; Mannion, C.; McLarney, J.K.; Kim, B. Sex cord-stromal and steroid cell tumors of the ovary. Radiographics, 1998, 18(6), 1523-1546.
[http://dx.doi.org/10.1148/radiographics.18.6.9821198] [PMID: 9821198]
[3]
Inada, Y.; Nakai, G.; Yamamoto, K.; Yamada, T.; Hirose, Y.; Terai, Y.; Ohmichi, M.; Narumi, Y. Rapidly growing juvenile granulosa cell tumor of the ovary arising in adult: a case report and review of the literature. J. Ovarian Res., 2018, 11(1), 100.
[http://dx.doi.org/10.1186/s13048-018-0474-0] [PMID: 30547828]
[4]
Seagle, B.L.; Ann, P.; Butler, S.; Shahabi, S. Ovarian granulosa cell tumor: A National Cancer Database study. Gynecol. Oncol., 2017, 146(2), 285-291.
[http://dx.doi.org/10.1016/j.ygyno.2017.05.020] [PMID: 28532858]
[5]
Young, R.H. Sex cord-stromal tumors of the ovary and testis: their similarities and differences with consideration of selected problems. Mod. Pathol., 2005, 18(Suppl. 2), S81-S98.
[http://dx.doi.org/10.1038/modpathol.3800311] [PMID: 15502809]
[6]
Gurumurthy, M.; Bryant, A.; Shanbhag, S. Effectiveness of different treatment modalities for the management of adult-onset granulosa cell tumours of the ovary (primary and recurrent). Cochrane Database Syst. Rev., 2014, 21(4), CD006912.
[http://dx.doi.org/10.1002/14651858.CD006912.pub2] [PMID: 24753008]
[7]
Colombo, N.; Parma, G.; Zanagnolo, V.; Insinga, A. Management of ovarian stromal cell tumors. J. Clin. Oncol., 2007, 25(20), 2944-2951.
[http://dx.doi.org/10.1200/JCO.2007.11.1005] [PMID: 17617526]
[8]
Lawal, T.O.; Patel, S.; Mahady, G.B. Validation of the ethnomedical use of nigerian plants for the treatment of cancer. International Conference on the Science of Botanicals, Oxford MI2017. Abstract-434.
[9]
Lawal, T.O.; Bamiduro, T.B.; Ofonmbuk, J.O.; Elufioye, T.O.; Adeniyi, B.A.; Mahady, G.B. Antibacterial effects of Anogeissus leiocarpus (DC.) Guill. & Perr. and Terminalia glaucescens Planch. ex Benth. on rapidly growing Mycobacteria species. Afr. J. Microbiol. Res., 2017, 11, 495-503. b
[http://dx.doi.org/10.5897/AJMR2016.8397]
[10]
Doyle, B.J.; Lawal, T.O.; Locklear, T.D.; Hernandez, L.; Perez, A.L.; Patel, U.; Patel, S.; Mahady, G.B. Isolation and identification of three new chromones from the leaves of Pimenta dioica with cytotoxic, oestrogenic and anti-oestrogenic effects. Pharm. Biol., 2018, 56(1), 235-244.
[http://dx.doi.org/10.1080/13880209.2018.1448873] [PMID: 29564971]
[11]
Zhang, H.; Vollmer, M.; De Geyter, M.; Litzistorf, Y.; Ladewig, A.; Dürrenberger, M.; Guggenheim, R.; Miny, P.; Holzgreve, W.; De Geyter, C. Characterization of an immortalized human granulosa cell line (COV434). Mol. Hum. Reprod., 2000, 6(2), 146-153.
[http://dx.doi.org/10.1093/molehr/6.2.146] [PMID: 10655456]
[12]
Patel, S.; Lawal, T.O.; Salamon, I.; Raut, N.; Wicks, S.M.; Mahady, G.B. Ribes nigrum L. (Grossulariaceae) and Sambus nigra L. (Adoxaceae) extracts enhance growth and inhibit apoptosis in rat L6 muscle cells. J. Food Nutr. Disord., 2017, 6, 3.
[13]
Raut, N.; Wicks, S.M.; Lawal, T.O.; Mahady, G.B. Epigenetic regulation of bone remodeling by natural compounds. Pharmacol. Res., 2019, 147, 104350.
[http://dx.doi.org/10.1016/j.phrs.2019.104350] [PMID: 31315065]
[14]
Liu, L.L.; Zhao, H.; Ma, T.F.; Ge, F.; Chen, C.S.; Zhang, Y.P. Identification of valid reference genes for the normalization of RT-qPCR expression studies in human breast cancer cell lines treated with and without transient transfection. PLoS One, 2015, 10(1), e0117058.
[http://dx.doi.org/10.1371/journal.pone.0117058] [PMID: 25617865]
[15]
Chen, X.; Sun, K.; Jiao, S.; Cai, N.; Zhao, X.; Zou, H.; Xie, Y.; Wang, Z.; Zhong, M.; Wei, L. High levels of SIRT1 expression enhance tumorigenesis and associate with a poor prognosis of colorectal carcinoma patients. Sci. Rep., 2014, 4, 7481.
[http://dx.doi.org/10.1038/srep07481] [PMID: 25500546]
[16]
Hoshyar, R.; Bathaie, S.Z.; Sadeghizadeh, M. Crocin triggers the apoptosis through increasing the Bax/Bcl-2 ratio and caspase activation in human gastric adenocarcinoma, AGS, cells. DNA Cell Biol., 2013, 32(2), 50-57.
[http://dx.doi.org/10.1089/dna.2012.1866] [PMID: 23347444]
[17]
Assunta, P.I.D.; da Conceição, E.D.; Borges, L.L.; Marciano de Paula, J.A. Development and validation of a HPLC-UV method for the evaluation of ellagic acid in liquid extracts of Eugenia uniflora L. (Myrtaceae) leaves and its ultrasound-assisted extraction optimization. Evidence-Based Complement Alternat Med., 2017, 2017, Article ID 1501038.
[18]
Cui, Q.; Du, R.; Anantpadma, M.; Schafer, A.; Hou, L.; Tian, J.; Davey, R.A.; Cheng, H.; Rong, L. Identification of ellagic acid from plant Rhodiola rosea L. as an anti-ebola virus entry inhibitor. Viruses, 2018, 10(4), E152.
[http://dx.doi.org/10.3390/v10040152] [PMID: 29584652]
[19]
Neves, N.A.; Stringheta, P.C.; Gómez-Alonso, S.; Hermosín-Gutiérrez, I. Flavonols and ellagic acid derivatives in peels of different species of jabuticaba (Plinia sp.) identified by HPLC-DAD-ESI/MSn. Food Chem., 2018, 252, 61-71.
[http://dx.doi.org/10.1016/j.foodchem.2018.01.078] [PMID: 29478564]
[20]
Asuzu, C.C.; Akin-Odanye, E.O.; Asuzu, M.C.; Holland, J. A socio-cultural study of traditional healers role in African health care. Infect. Agent. Cancer, 2019, 14, 15.
[http://dx.doi.org/10.1186/s13027-019-0232-y] [PMID: 31249608]
[21]
Batta, H.E. Press coverage of traditional medical practice in Nigeria. J. Commun., 2012, 3(2), 75-89.
[http://dx.doi.org/10.1080/0976691X.2012.11884798]
[22]
Ezeome, E.R. Delays in presentation and treatment of breast cancer in Enugu, Nigeria. Niger. J. Clin. Pract., 2010, 13(3), 311-316.
[http://dx.doi.org/10.4103/1119-3077.86775] [PMID: 20857792]
[23]
Ukwenya, A.Y.; Yusufu, L.M.D.; Nmadu, P.T.; Garba, E.S.; Ahmed, A. Delayed treatment of symptomatic breast cancer: The experience from Kaduna, Nigeria. S. Afr. J. Surg., 2008, 46(4), 106-110.
[PMID: 19051953]
[24]
Bate-Smith, E.C.; Harborne, J.B. Differences in flavonoids content between fresh and herbarium leaf tissue in Dillenia. Phytochemistry, 1975, 10(5), 1055-1058.
[http://dx.doi.org/10.1016/S0031-9422(00)89938-0]
[25]
Barua, C.C.; Yasmin, N.; Buragohain, L. A review update on Dillenia indica, its morphology, phytochemistry and pharmacological activity with reference to its anticancer activity. MOJ Bioequiv Availab, 2018, 5(5), 244-254.
[26]
Gandhi, D.; Mehta, P. Dillenia indica Linn. and Dillenia pentagyna Roxb.: Pharmacognostic, phytochemical and therapeutic aspects. J. Appl. Pharm. Sci., 2013, 3, 134-142.
[27]
Saowakhon, S.; Manosroi, J.; Manosroi, A. Anti-proliferation activities of Thai Lanna medicinal plant recipes in cancer cell lines by SRB assay. J. Thai Tradit. Alternat. Med., 2008, 6(Suppl 2)
[28]
Dalziel, J.M. The useful plants of west tropical Africa; Crown Agents: London, 1937.
[29]
Salau, A.K.; Yakubu, M.T.; Oladiji, A.T. Cytotoxic activity of aqueous extracts of Anogeissus leiocarpus and Terminalia avicennioides root barks against Ehrlich ascites carcinoma cells. Indian J. Pharmacol., 2013, 45(4), 381-385.
[http://dx.doi.org/10.4103/0253-7613.115023] [PMID: 24014915]
[30]
Olugbami, J.O.; Damoiseaux, R.; France, B.; Onibiyo, E.M.; Gbadegesin, M.A.; Sharma, S.; Gimzewski, J.K.; Odunola, O.A. A comparative assessment of antiproliferative properties of resveratrol and ethanol leaf extract of Anogeissus leiocarpus (DC) Guill. & Perr. against HepG2 hepatocarcinoma cells. BMC Complement. Altern. Med., 2017, 17(1), 381.
[http://dx.doi.org/10.1186/s12906-017-1873-2] [PMID: 28768515]
[31]
Hassan, L.E.A.; Al-Suede, F.S.; Fadul, S.M.; Abdul Majid, A.M.S. Evaluation of antioxidant, antiangiogenic and antitumor properties of Anogeissus leiocarpus against colon cancer. Angiotherapy, 2018, 1(2), 56-66.
[http://dx.doi.org/10.25163/angiotherapy.1200021526100818]
[32]
Tilly, J.L.; Tilly, K.I.; Kenton, M.L.; Johnson, A.L. Expression of members of the bcl-2 gene family in the immature rat ovary: equine chorionic gonadotropin-mediated inhibition of granulosa cell apoptosis is associated with decreased bax and constitutive bcl-2 and bcl-xlong messenger ribonucleic acid levels. Endocrinology, 1995, 136(1), 232-241.
[http://dx.doi.org/10.1210/endo.136.1.7828536] [PMID: 7828536]
[33]
Campbell, K.J.; Tait, S.W.G. Targeting BCL-2 regulated apoptosis in cancer. Open Biol., 2018, 8(5), 180002.
[http://dx.doi.org/10.1098/rsob.180002] [PMID: 29769323]
[34]
Zhai, P.; Zeng, J.; Tan, N.; Wang, J.; Huang, L.; She, W. Effects of vitamin C on A549 cell proliferation, apoptosis and expressions of caspase, survivin. Zhongguo Fei Ai Za Zhi, 2010, 13(2), 89-93.
[PMID: 20673497]
[35]
Fenwick, M.A.; Hurst, P.R. Immunohistochemical localization of active caspase-3 in the mouse ovary: Growth and atresia of small follicles. Reproduction, 2002, 124(5), 659-665.
[http://dx.doi.org/10.1530/rep.0.1240659] [PMID: 12417004]
[36]
Choi, A.M.; Ryter, S.W.; Levine, B. Autophagy in human health and disease. N. Engl. J. Med., 2013, 368(7), 651-662.
[http://dx.doi.org/10.1056/NEJMra1205406] [PMID: 23406030]
[37]
Santana-Codina, N.; Mancias, J.D.; Kimmelman, A.C. The role of autophagy in cancer. Annu. Rev. Cancer Biol., 2017, 1, 19-39.
[http://dx.doi.org/10.1146/annurev-cancerbio-041816-122338] [PMID: 31119201]
[38]
White, E. The role for autophagy in cancer. J. Clin. Invest., 2015, 125(1), 42-46.
[http://dx.doi.org/10.1172/JCI73941] [PMID: 25654549]
[39]
Jung, C.H.; Ro, S.H.; Cao, J.; Otto, N.M.; Kim, D.H. mTOR regulation of autophagy. FEBS Lett., 2010, 584(7), 1287-1295.
[http://dx.doi.org/10.1016/j.febslet.2010.01.017] [PMID: 20083114]
[40]
Kimmelman, A.C. The dynamic nature of autophagy in cancer. Genes Dev., 2011, 25(19), 1999-2010.
[http://dx.doi.org/10.1101/gad.17558811] [PMID: 21979913]
[41]
Ceci, C.; Lacal, P.M.; Tentori, L.; De Martino, M.G.; Miano, R.; Graziani, G. Experimental evidence of the antitumor, antimetastatic and antiangiogenic activity of ellagic acid. Nutrients, 2018, 10(11), E1756.
[http://dx.doi.org/10.3390/nu10111756] [PMID: 30441769]
[42]
Chung, Y.C.; Lu, L.C.; Tsai, M.H.; Chen, Y.J.; Chen, Y.Y.; Yao, S.P.; Hsu, C.P. The inhibitory effects of ellagic acid on cell growth of ovarian cancer cells. Evid. Based Complement. Alt. Med., 2013. Article ID 306705
[43]
Eskra, J.N.; Schlicht, M.J.; Bosland, M.C. Effects of Black Raspberries and their ellagic acid and anthocyanin constituents on taxane chemotherapy of castration-resistant prostate cancer cells. Sci. Rep., 2019, 9(1), 4367.
[http://dx.doi.org/10.1038/s41598-019-39589-1] [PMID: 30867440]
[44]
Jaman, M.S.; Sayeed, M.A. Ellagic acid, sulforaphane, and ursolic acid in the prevention and therapy of breast cancer: Current evidence and future perspectives. Breast Cancer, 2018, 25(5), 517-528.
[http://dx.doi.org/10.1007/s12282-018-0866-4] [PMID: 29725861]
[45]
Liu, H.; Zeng, Z.; Wang, S.; Li, T.; Mastriani, E.; Li, Q.H.; Bao, H.X.; Zhou, Y.J.; Wang, X.; Liu, Y.; Liu, W.; Hu, S.; Gao, S.; Yu, M.; Qi, Y.; Shen, Z.; Wang, H.; Gao, T.; Dong, L.; Johnston, R.N.; Liu, S.L. Main components of pomegranate, ellagic acid and luteolin, inhibit metastasis of ovarian cancer by down-regulating MMP2 and MMP9. Cancer Biol. Ther., 2017, 18(12), 990-999.
[http://dx.doi.org/10.1080/15384047.2017.1394542] [PMID: 29173024]
[46]
Silva, J.S.; Moura, M.D.; Oliveira, R.A.G.; Diniz, M.F.F.; Barbosa-Filho, J.M. Natural product inhibitors of ovarian neoplasia. Phytomedicine, 2003, 10(2-3), 221-232.
[http://dx.doi.org/10.1078/094471103321659988] [PMID: 12725581]

Rights & Permissions Print Cite
Article Metrics
14
1
© 2024 Bentham Science Publishers | Privacy Policy