Effect of African Leaves (Vernonia amygdalina Delile) on the Development of T47D Breast Cancer Cells
Article Sidebar
Main Article Content
Abstract
Cancer is still a health problem in the world. The number of sufferers and deaths from cancer
continues to increase from year to year, especially breast cancer. Cancer treatment is often
associated with high toxicity and low selectivity, and the emergence of resistance to
chemotherapeutic agents is a serious problem. Therefore, the development of new anticancer
agents is a priority. This research provides information regarding the potential of the Vernonia
amygdaline Delile plant for the development of breast cancer. Several studies show that this
plant has the potential to be used as an anticancer agent. The research was conducted by
extracting and fractionating this plant's leaves and then assessing the cytotoxic effect on T47D
cell viability using Microtetrazolium. Next, cell cycle inhibition, apoptosis, p53 and Akt
protein expression were analyzed using flow cytometry techniques. The results showed that
the dichloromethane fraction had the highest yield. The dichloromethane fraction had the best
IC50 value, 76.72 ± 1.79 μg/mL. Able to inhibit the cell cycle in the G2/M phase, stimulate
apoptosis, increase p53 protein expression and inhibit Akt protein expression in T47D cells.
The dichloromethane fraction can potentially be developed in treating breast cancer
development.
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
References
Ferlay J, Colombet M, Soerjomataram I, Parkin DM, Piñeros M,
Znaor A, F Bray. Cancer statistics for the year 2020: An
overview. Int J Cancer. 2021; 149:778–89. Doi:
1002/ijc.33588.
WHO (2024): News world cancer day
https://www.emro.who.int/media/news/world-cancer-day2024.html
Obafemi FA, Umahi-Ottah G. A review of global cancer
prevalence and therapy. J Cancer Res Treat Prev. 2023;
(3):128-147. Doi: 10.37191/Mapsci-JCRTP-1(3)-011
Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics
CA Cancer J Clin. 2023; 73:17–48. Doi:
3322/caac.21763.
Hunter N, English S, Nguyen V, Vinayak S, Linden HM, Specht
JM, Gwin WR, Yung RL, Achkar MA. Experiences of patients
with metastatic breast cancer: A qualitative study. JCO Oncol
Pract. 2023; 19:346–346. Doi:
1200/OP.2023.19.11_suppl.346.
Guité-Verret A, Vachon M. The incurable metastatic breast
cancer experience through metaphors: the fight and the
unveiling. Int J Qual Stud Health Well-Being. 2021; 16. Doi:
1080/17482631.2021.1971597.
Tapia M, Hernando C, Martínez MT, Burgués O, TebarSánchez C, Lameirinhas A, A Ágreda-Roca, S Torres-Ruiz, I
Garrido-Cano, A Lluch, B Bermejo, P Eroles. Clinical impact of
new treatment strategies for HER2-positive metastatic breast
cancer patients with resistance to classical anti-her therapies.
Cancers (Basel). 2023; 15:4522. Doi:
3390/cancers15184522.
AlNowak J, Wambebe C, Mukonzo J, Katuura E. Cytotoxic
activity of combining molecular iodine and dihydroartemisinin
with methanolextracts of Carica papaya Linn and Vernonia
amygdalina Delile leaves against MCF-7 and MDA-MB-231
breast cancer cell lines. Trop J Nat Prod Res. 2021; 5(3):485-
Doi: 10.26538/tjnpr/v5i3.12
Koual M, Tomkiewicz C, Cano-Sancho G, Antignac J-P, Bats
A-S, Coumoul X. Environmental chemicals, breast cancer
progression and drug resistance. Environmental Health. 2020;
:117. Doi: 10.1186/s12940-020-00670-2.
Dong X, Bai X, Ni J, Zhang H, Duan W, Graham P, Y Li.
Exosomes and breast cancer drug resistance. Cell death &
disease. 2020; 11:987. Doi: 10.1038/s41419-020-03189-z
Kinnel B, Singh SK, Oprea-Ilies G, Singh R. Targeted therapy
and mechanisms of drug resistance in breast cancer. Cancers
(Basel). 2023; 15:1320. Doi: 10.3390/cancers15041320.
Kang Y. Landscape of NcRNAs involved in drug resistance of
breast cancer. Clinical and Translational Oncology. 2023;
:1869–92. Doi: 10.1007/s12094-023-03189-3.
Singh NK, Yadav AK, Sirohi P, Rani M, Saraswat S, Singh MP,
Mani A, Srivastava S. Anticancer activity of herbal medicine:
mechanism of action. Anticancer plants: mechanisms and
molecular interactions. Springer Singapore. 2018; 165–96. Doi:
1007/978-981-10-8417-1_7.
Syahputra RA, Harahap U, Dalimunthe A, Pandapotan M, Satria
D. Protective effect of Vernonia amygdalina Delile against
doxorubicin-induced cardiotoxicity. Heliyon. 2021; 7:07434.
Doi: 10.1016/j.heliyon.2021.e07434.
Bihonegn T, Giday M, Yimer G, Animut A, Sisay M.
Antimalarial activity of hydromethanolic extract and its solvent
fractions of Vernonia amygdalina leaves in mice infected with
Plasmodium berghei. SAGE Open Med. 2019;
:205031211984976. Doi: 10.1177/2050312119849766.
Abosi AO, Raseroka BH. In vivo antimalarial activity of
Vernonia amygdalina. Br J Biomed Sci. 2003; 60:89–91. Doi:
1080/09674845.2003.11783680.
Nguyen TXT, Dang DL, Ngo VQ, Trinh TC, Trinh QN, Do TD,
Thanh TTT. Anti-inflammatory activity of a new compound
from Vernonia amygdalina. Natural Product Research. 2021;
:5160–5. Doi: 10.1080/14786419.2020.1788556.
Muhammad M, De Lux E, Satria D, Nasri. Variation of
extraction method of Vernonia amygdalina Delile leaves
ethanol extract as antibacterial against Streptococcus mutans
and Candida albicans. 2023; 030002. Doi: 10.1063/5.0136221.
Egedigwe CA, Ijeh II, Okafor PN, Ejike CECC. Aqueous and
methanol extracts of Vernonia amygdalina leaves exert their
anti-obesity effects through the modulation of appetiteregulatory hormones. Pharm Biol. 2016; 54:3232–6. Doi: 10.1080/13880209.2016.1216135.
Satria D. The effect of extraction method of Vernonia
amygdalina Delile. leaves on cardiotonic effect. Farmacia.
; 71:392–6. Doi: 10.31925/farmacia.2023.2.20.
Satria D, Harahap U, Dalimunthe A, Septama AW, Hertiani T,
Nasri N. Synergistic antibacterial effect of ethyl acetate fraction
of Vernonia amygdalina Delile leaves with tetracycline against
clinical isolate methicillin-resistant Staphylococcus aureus
(MRSA) and Pseudomonas aeruginosa. Adv Pharmacol Pharm
Sci. 2023; 1–11. Doi: 10.1155/2023/2259534.
Hasibuan PAZ, Sitorus RKUAB, Hermawan A, Huda F,
Waruwu SB, Satria D. Anticancer activity of the ethylacetate
fraction of Vernonia amygdalina Delile towards overexpression
of HER-2 breast cancer cell lines. Pharmacia. 2024; 71:1–8.
Doi: 10.3897/pharmacia.71.e125788
Anh HLT, Vinh LB, Lien LT, Cuong PV, Arai M, Ha TP, Lin
HN, Dat TTH, Cuong LCV, Kim YH. In vitro study on αamylase and α-glucosidase inhibitory activities of a new
stigmastane-type steroid saponin from the leaves of Vernonia
amygdalina. Nat Prod Res. 2021; 35:873–9. Doi:
1080/14786419.2019.1607853.
Van PcP, Ngo Van H, Quang MB, Duong Thanh N, Nguyen
Van D, Thanh T Do, Minh NT, Thu HNT, Quang TN, Do TT,
Thanh LP, Thu HDT, Tuan AHL. Stigmastane-type steroid
saponins from the leaves of Vernonia amygdalina and their α -
glucosidase and xanthine oxidase inhibitory activities. Nat Prod
Res. 2024; 38:601–6. Doi: 10.1080/14786419.2023.2188589.
Hasibuan PAZ, Harahap U, Sitorus P, Satria D. The anticancer
activities of Vernonia amygdalina Delile. leaves on 4T1 breast
cancer cells through phosphoinositide 3-kinase (PI3K) pathway.
Heliyon. 2020; 6:04449. Doi: 10.1016/j.heliyon.2020.e04449.
Nerdy N, Margata L, Meliala L, Purba MS, Sembiring BM,
Ginting S, Bakri TK. In silico evaluation of the
physicochemical, pharmacokinetics, and toxicity profiles of
sesquiterpene lactones of south african leaf (Vernonia amygdalina Delile). Trop J Nat Prod Res. 2021; 5(10):1835-1840. Doi: 10.26538/tjnpr/v5i10.21
Evbuomwan L, Chukwuka EP, Obazenu EI, Ilevbare L.
Antibacterial activity of Vernonia amygdalina leaf extracts
against multidrug resistant bacterial isolates. J. Appl. Sci.
Environ. Manag. 2018; 22(1):17–21.
Oladele JO, Oyeleke OM, Oladele OT, Oladiji AT. Covid-19
treatment: investigation on the phytochemical constituents of
Vernonia amygdalina as potential coronavirus-2 inhibitors.
Comput. Toxicol. 2021; 18.
Yusoff SF, Haron FF, Mohamed TMM, Asib N, Sakimin SZ,
Abu KF. Ismail SI. Antifungal activity and phytochemical
screening of Vernonia amygdalina extract against Botrytis
cinerea causing gray mold disease on tomato fruits. Biology.
; 9(9):286.
Hasibuan PAZ, Lubis MF, Keliat JM, Azizah N. Cytotoxic test
combination of ethyl acetate extract africant leaves (Vernonia
amygdalina Delile) and gemcitabine on PANC-1 cells. AIP
Conf. Proc. 2023; 2626:1:030004. Doi: 10.1063/5.0149754.
Xi X, Wang J, Qin Y, You Y, Huang W, Zhan J. The biphasic
effect of flavonoids on oxidative stress and cell proliferation in
breast cancer cells. Antioxidants. 2022; 11:622. Doi:
3390/antiox11040622.
Sugiura R, Satoh R, Takasaki T. ERK: A double-edged sword in
cancer. ERK-dependent apoptosis as a potential therapeutic
strategy for cancer. Cells. 2021; 10:2509. Doi:
3390/cells10102509.
Khongkaew P, Wattanaarsakit P, Papadopoulos KI,
Chaemsawang W. Antioxidant effects and in vitro cytotoxicity
on human cancer cell lines of flavonoid-rich flamboyant
(Delonix regia (Bojer) Raf.) flower extract. Curr Pharm
Biotechnol. 2021; 22:1821–31. Doi:
2174/1389201021666201029154746.
Hatono M, Ikeda H, Suzuki Y, Kajiwara Y, Kawada K,
Tsukioki T, Kochi M, Suzawa K, Iwamoto T, Yamamoto H,
Shien T, Yamane M, Taira N, Doihara H, Toyooka S. Effect of
isoflavones on breast cancer cell development and their impact
on breast cancer treatments. Breast cancer research and
treatment. 2021; 185:307–16. Doi: 10.1007/s10549-020-05957-
z.
Raina R, Hussain A, Sharma R. Molecular insight into apoptosis
mediated by flavones in cancer (review). World Acad Sci J.
; 2:3. Doi: 10.3892/wasj.2020.47.
Hou Y, Shang C, Meng T, Lou W. Anticancer potential of
cardiac glycosides and steroid-azole hybrids. Steroids. 2021;
:108852. Doi: 10.1016/j.steroids.2021.108852.
Reddy D, Kumavath R, Barh D, Azevedo V, Ghosh P.
Anticancer and antiviral properties of cardiac glycosides: a
review to explore the mechanism of actions. Molecules. 2020;
:3596. Doi: 10.3390/molecules25163596.
Liu M, Huang Q, A J, Li L, Li X, Zhang Z, Dong JT. The
cardiac glycoside deslanoside exerts anticancer activity in
prostate cancer cells by modulating multiple signaling
pathways. Cancers (Basel). 2021; 13:5809. Doi:
3390/cancers13225809.
Du J, Jiang L, Chen F, Hu H, Zhou M. Cardiac glycoside
ouabain exerts anticancer activity via downregulation of
STAT3. Front Oncol. 2021; 11. Doi:
3389/fonc.2021.684316.
Satria D, Silalahi J, Haro G, Ilyas S, Hasibuan ZPA. Chemical
analysis and cytotoxic activity of nhexane fraction of
Zanthoxylum acanthopodium DC. fruits. Rasayan Journal of
Chemistry. 2019; 12:803–8. Doi: 10.31788/RJC.2019.1225180.
Wang MM, Li YN, Ming WK, Wu PF, Yi P, Gong Z, Hao X,
Yuan C. Bioassay-guided isolation of human carboxylesterase 2
inhibitory and antioxidant constituents from Laportea bulbifera:
inhibition interactions and molecular mechanism. Arabian
Journal of Chemistry. 2022; 15:103723. Doi:
1016/j.arabjc.2022.103723.
Dalimunthe A, Hasibuan PAZ, Satria D. The PI3KCA and AKT
inhibitory activities of Litsea cubeba Lour. fruits and
heartwoods towards Hela cells. Open Access Maced J Med Sci.
; 7:1422–4. Doi: 10.3889/oamjms.2019.317.
Kathiresan K, Ramakrishnan M. Biosynthesis of iron oxide
nanoparticles from dates, characterization, and investigation of
anticarcinogenic and antimicrobial properties. Kuwait J Sci.
; 49(4):1-14. Doi: 10.48129/kjs.13181.
Gómez de Cedrón M, Navarro del Hierro J, Reguero M, Wagner
S, Bouzas A, Quijada-Freire A, Reglero G, Martín D, Ramírez
de Molina A. Saponin-Rich Extracts and Their Acid
Hydrolysates Differentially Target Colorectal Cancer
Metabolism in the Frame of Precision Nutrition. Cancers
(Basel) 2020;12:3399. https://doi.org/10.3390/cancers12113399.
Rollando R, Monica E, Aftoni MH. In vitro cytotoxic potential
of Sterculia quadrifida leaf extract against human breast cancer
cell lines. TropJ Nat Prod Res. 2022; 6(8):1228-1232. Doi:
26538/tjnpr/v6i8.12
Ho Y, Suphrom N, Daowtak K, Potup P, Thongsri Y,
Usuwanthim K. Anticancer effect of Citrus hystrix DC. leaf
extract and its bioactive constituents citronellol and, citronellal
on the triple negative breast cancer MDA-MB-231 cell line.
Pharmaceuticals. 2020; 13:476. Doi: 10.3390/ph13120476.
Rodríguez De Luna SL, Ramírez-Garza RE, Serna Saldívar SO.
Environmentally friendly methods for flavonoid extraction from
plant material: impact of their operating conditions on yield and
antioxidant properties. The Scientific World Journal. 2020; 1–
Doi: 10.1155/2020/6792069.
Lefebvre T, Destandau E, Lesellier E. Selective extraction of
bioactive compounds from plants using recent extraction
techniques: a review. J Chromatogr A. 2021; 1635:461770. Doi:
1016/j.chroma.2020.461770.
Dalimunthe A, Satria D, Sitorus P, Harahap U, Angela IFD,
Waruwu SB. Cardioprotective effect of hydroalcohol extract of
andaliman (Zanthoxylum acanthopodium DC.) fruits on
doxorubicin-induced rats. Pharmaceuticals. 2024; 17:359. Doi:
3390/ph17030359.
Marrelli M, Argentieri MP, Avato P, Conforti F. Lobularia
maritima (L.) Desv. aerial parts methanolic extract: in vitro
screening of biological activity. Plants. 2020; 9:89. Doi:
3390/plants9010089.
Hasibuan PAZ, Keliat JM, Lubis MF, Nasution A. The ethyl
acetate extract of Vernonia amygdalina leaf ameliorates
gemcitabine effect against migration and invasion of PANC-1
cells via down-regulation the VEGF, COX2, and RAS/MEK
pathways. Saudi Pharmaceutical Journal. 2024; 32:101872. Doi:
1016/j.jsps.2023.101872.
Sitorus P, Keliat JM, Asfianti V, Muhammad M, Satria D. A
literature review of Artocarpus lacucha focusing on the
phytochemical constituents and pharmacological properties of
the plant. Molecules. 2022; 27:6940. Doi:
3390/molecules27206940.
Hermawan A, Satria D, Hasibuan PAZ, Huda F, Tafrihan AS,
Fatimah N, Putri DDP. Identification of potential target genes of
cardiac glycosides from Vernonia amygdalina Delile in HER2+
breast cancer cells. South African Journal of Botany. 2024;
:401–18. Doi: 10.1016/j.sajb.2023.12.002.
Ghasemi M, Turnbull T, Sebastian S, Kempson I. The MTT
assay: utility, limitations, pitfalls, and interpretation in bulk and
single-cell analysis. Int J Mol Sci. 2021; 22:12827. Doi:
3390/ijms222312827.
Oktavia S, Wahyuni FS, Hasmiwati, Amir A. Piperine acts as an
anticancer agent by reducing cyclooxygenase-2 activity and
inducing apoptosis by activating p53 in HeLa cells. Trop J Nat
Prod Res. 2024; 8(2):6142-6146. Doi: 10.26538/tjnpr/v8i2.11
Hudan SH, Praticia VM. Examine the pharmacological effects
of African leaves (Vernonia amygdalina Del) and the active
compounds contained therein. Jurnal Riset Farmasi. 2022; 9–14.
Doi: 10.29313/jrf.v2i1.700.
Manohar SM, Shah P, Nair A. Flow cytometry: principles,
applications and recent advances. Bioanalysis. 2021; 13:181–98.
Doi: 10.4155/bio-2020-0267.
Cheung M, Campbell JJ, Whitby L, Thomas RJ, Braybrook J,
Petzing J. Current trends in flow cytometry automated data
analysis software. Cytometry Part A. 2021; 99:1007–21. Doi:
1002/cyto.a.24320.
Krętowski R, Jabłońska-Trypuć A, Cechowska-Pasko M. The
effect of silica nanoparticles (SiNPs) on cytotoxicity, induction
of oxidative stress and apoptosis in breast cancer cell lines. Int J
Mol Sci. 2023; 24:2037. Doi: 10.3390/ijms24032037.
Cummings BS, Schnellmann RG. Measurement of cell death in
mammalian cells. Curr Protoc Pharmacol. 2004; 25. Doi:
1002/0471141755.ph1208s25.
Micoud F, Mandrand B, Malcus‐Vocanson C. Comparison of
several techniques for the detection of apoptotic astrocytes in
vitro. Cell Prolif. 2001; 34:99–113. Doi: 10.1046/j.1365-
2001.00201x.
Hu XM, Li ZX, Lin RH, Shan JQ, Yu QW, Wang RX, Liao LS,
Yan WT, Wang Z, Shang L, Huang Y, Zhang Q, Xiong K.
Guidelines for regulated cell death assays: a systematic
summary, a categorical comparison, a prospective. Front Cell
Dev Biol. 2021; 9. Doi: 10.3389/fcell.2021.634690.
Istiqomah MA, Hasibuan PAZ, Sumaiyah S, Yusraini E, Oku H,
Basyuni M. Anticancer effects of polyisoprenoid from Nypa
fruticans leaves by controlling expression of p53, EGFR, PI3K,
AKT1, and mTOR genes in colon cancer (WiDr) cells. Nat Prod
Commun. 2020; 15:1934578X2091841. Doi:
1177/1934578X20918412.
Marvalim C, Datta A, Lee SC. Role of p53 in breast cancer
progression: an insight into p53 targeted therapy. Theranostics.
; 13:1421–42. Doi: 10.7150/thno.81847.
Hua H, Zhang H, Chen J, Wang J, Liu J, Jiang Y. Targeting Akt
in cancer for precision therapy. J Hematol Oncol. 2021; 14:128.
Doi: 10.1186/s13045-021-01137-8.
Tsai PJ, Lai YH, Manne RK, Tsai YS, Sarbassov D, Lin HK.
Akt: a key transducer in cancer. J Biomed Sci. 2022; 29:76. Doi:
1186/s12929-022-00860-9.
Parsons CM, Muilenburg D, Bowles TL, Virudachalam S, Bold
RJ. The role of Akt activation in the response to chemotherapy
in pancreatic cancer. Anticancer Res. 2010; 30:3279–89.
Mahmood MA, Abd AH, Kadhim EJ. Investigating the impact
of phenolic and terpene fractions extracted from Prunus
arabicaon p53 protein expression in AMJ13 and SK-GT-4
human cancer cell lines. Trop J Nat Prod Res. 2023; 7(11):5266-
Doi: 10.26538/tjnpr/v7i11.35