Document Type : Original Research Article
Authors
- Muhammad Fauzan Lubis 1
- Sumaiyah Sumaiyah 2
- Embun Suci Nasution 3
- Ririn Astyka 1
- Masfria Masfria 4
- Hafid Syahputra 4
- Carlos Nofanolo Lase 1
1 Department of Pharmaceutical Biology, Universitas Sumatera Utara, Medan, 20222, Indonesia
2 Department of Pharmaceutical Technology, Universitas Sumatera Utara, Medan, 20222, Indonesia
3 Department of Pharmacology, Universitas Sumatera Utara, Medan, 20222, Indonesia
4 Department of Pharmaceutical Chemistry, Universitas Sumatera Utara, Medan, 20222, Indonesia
10.48309/ecc.2023.417046.1684
Abstract
One of the plants that potential to develop as an anticancer agent is Duku leaf (Lansium domesticum Corr.). From previous studies, Duku leaf extract had cytotoxic activity against several cancerous cell lines. The aim of this study was to determine the cytotoxic activity of crude and purified extracts of Duku leaf against MCF-7 and HTB-183 cell lines. The crude extract of Duku leaf was obtained using maceration in ethanol absolute. The vacuum liquid chromatography with a gradient mobile phase was performed to obtain the purified extracts. The crude and purified extracts were observed to inhibit MCF-7 and HTB-183 cells using 3-(4,5- dimethyl thiazol 2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. The antioxidant properties of samples were determined using radical DPPH scavenging activity. The data was collected and analyzed to provide the inhibitory concentration 50 (IC50) and Pearson’s correlation was analyzed to describe the correlation between cytotoxic and antioxidant properties. Five purified extracts were obtained and tested against MCF-7 and HTB-183. The purified extract D has stronger anticancer and antioxidant activities than other samples with IC50 of 56.26 ± 3.11 µg/mL, 70.94 ± 2.92 µg/mL, and 53.65 ± 1.55 µg/mL, respectively (p < 0.05). We confirmed that cytotoxic activity has a strong correlation with antioxidant properties. Furthermore, the active compounds of purified extract D needed to be investigated and tested against MCF-7 and HTB-183 to explore the possible anticancer mechanisms.
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[1] J. Ferlay, M. Colombet, I. Soerjomataram, D.M. Parkin, M. Pineros, A. Znaor, F. Bray, Cancer statistics for the year 2020: An overview, Int. J. Cancer, 2021, 149, 778-789. [Crossref], [Google Scholar], [Publisher]
[2] R.L. Siegel, K.D. Miller, N.S. Wagle, A. Jemal, Cancer statistics, 2023, CA Cancer J Clin, 2022, 73, 17-48,. [Crossref], [Google Scholar], [Publisher]
[3] A. Leiter, R.R. Veluswamy, J.P. Wisnivesky, The global burden of lung cancer: current status and future trends, Nat Rev Clin Oncol, 2023, 20, 624-639. [Crossref], [Google Scholar], [Publisher]
[4] W. Ju, R. Zheng, S. Zhang, H. Zeng, K. Sun, S. Wang, R. Chen, L. Li, W. Wei, J. He, Cancer statistics in Chinese older people, 2022: current burden, time trends, and comparisons with the US, Japan, and the Republic of Korea, China Life Sci, 2023, 66, 1079-1091. [Crossref], [Google Scholar], [Publisher]
[5] B. Ng, H. Puspitaningtyas, J.A. Wiranata, S.H. Hutajulu, I. Widodo, N. Anggorowati, G.Y. Sanjaya, L. Lazuardi, P. Sripan, Breast cancer incidence in Yogyakarta, Indonesia from 2008–2019: A cross-sectional study using trend analysis and geographical information system, PloS one, 2023, 18, e0288073. [Crossref], [Google Scholar], [Publisher]
[6] O.D. Asmara, E.D. Tenda, G. Singh, C.W. Pitoyo, C.M. Rumende, W. Rajabto, N.R. Ananda, I. Trisnawati, E. Budiyono, H.F. Thahadian, E.C. Boerma, A. Faisal, D. Hutagaol, W. Soeharto, F. Radityamurti, E. Marfiani, P.Z. Romadhon, F.N. Kholis, H. Suryadinata, A.Y. Soeroto, S.A. Gondhowiardjo, W.H. van Geffen, Lung cancer in Indonesia, J. Thorac Oncol., 2023, 18, 1134-1145. [Crossref], [Google Scholar], [Publisher]
[7] S. Hashem, T.A. Ali, S. Akhtar, S. Nisar, G. Sageena, S. Ali, S. Al-Mannai, L. Therachiyil, R. Mir, I. Elfaki, M.M. Mir, F. Jamal, T. Masoodi, S. Uddin, M. Singh, M. Haris, M. Macha, A.A. Bhat, Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents, Biomed. Pharmacother., 2022, 150, 113054. [Crossref], [Google Scholar], [Publisher]
[8] S.M. Kasim, N.T. Abdulaziz, Y.F. Mustafa, Synthesis and biomedical activities of coumarins derived from natural phenolic acids, J. Med. Chem. Sci., 2022, 5, 546-560. [Crossref], [Google Scholar], [Publisher]
[9] Y.F. Mustafa, M.K. Bashir, M.K. Oglah, Influence of albocarbon-cylic hybridization on biomedical activities: a review, J. Med. Chem. Sci., 2022, 5, 550-568. [Crossref], [Publisher]
[10] Elfahmi, H.J. Woerdenbag, O. Kayser, Jamu: Indonesian traditional herbal medicine towards rational phytopharmacological use, J. Herb. Med., 2014, 4, 51-73. [Crossref], [Google Scholar], [Publisher]
[11] A. Oladipupo, C. Alaribe, T. Akintemi, H. Coker, Effect of Phaulopsis falcisepala (Acanthaceae) leaves and stems on mitotic arrest and induction of chromosomal changes in Meristematic Cells of Allium Cepa, Prog Chem Biochem Res, 2021, 4, 134-147. [Crossref], [Google Scholar], [Publisher]
[12] C. Ukwubile, E. Ikpefan, M. Bingari, L. Tam, Acute and subchronic toxicity profiles of Melastomastrum capitatum (Vahl) Fern. (Melastomataceae) root aqueous extract in Swiss albino mice, Prog Chem Biochem Res, 2019, 2, 74-83. [Crossref], [Google Scholar], [Publisher]
[13] P.A. Kalvanagh, Y.A.A. Kalvanagh, New therapeutic approach based on silymarin in the treatment of breast cancer, Adv. J. Chem. Sect. B. Nat. Prod. Med. Chem., 2023, 5, 75-85. [Crossref], [Pdf], [Publisher]
[14] L. Ghaderi, Relationship between FGFR2 gene RS2981582 polymorphism and breast cancer risk factors in women candidates for surgery, Adv. J. Chem. Sect. B. Nat. Prod. Med. Chem., 2023, 5, 98-107. [Crossref], [Pdf], [Publisher]
[15] M. Zehravi, M. Maqbool, I. Ara, Curcumin– A promising phytocompound of immense potential, Adv. J. Chem. Sect. B. Nat. Prod. Med. Chem., 2021, 3, 271-276. [Crossref], [Google Scholar], [Publisher]
[16] M. Greenwell, P.K. Rahman, Medicinal plants: their use in anticancer treatment, Int J Pharm Sci Res, 2015, 1, 4103-4112. [Crossref], [Google Scholar], [Publisher]
[17] F.Z. Kazemabadi, A. Heydarinasab, A. Akbarzadehkhiyavi, M. Ardjmand, Development, optimization and in vitro evaluation of etoposide loaded lipid polymer hybrid nanoparticles for controlled drug delivery on lung cancer, Chem. Methodol., 2020, 5, 135-152. [Crossref], [Google Scholar], [Publisher]
[18] M.F. Lubis, P.A.Z. Hasibuan, H. Syahputra, R. Astyka, A review on phytochemicals and pharmacological activities as ethnomedicinal uses of Duku (Lansium domesticum Corr.), Open Access Maced J Med Sci, 2022, 10, 57-65. [Crossref], [Google Scholar], [Publisher]
[19] A. Manosroi, P. Jantrawut, M. Sainakham, W. Manosroi, J. Manosroi, Anticancer activities of the extract from Longkong (Lansium domesticum) young fruits, Pharm Biol, 2012, 50, 1397-1407. [Crossref], [Google Scholar], [Publisher]
[20] S.E. Sinaga, F.F. Abdullah, U. Supratman, T. Mayanti, R. Maharani, Isolation and Structure Determination of Stigmaterol from the Stem Bark of Lansium domesticum Corr. Cv. Kokossan, Chimica et Natura Acta, 2022, 10, 106-111. [Crossref], [Google Scholar], [Publisher]
[21] R.M.A. Khalili, J.M. Noratiqah, R. Norhaslinda, A.H. Norhayati, B.A. Amin, A. Roslan, A.L.A. Zubaidi, Cytotoxicity effect and morphological study of different Duku (Lansium domesticum corr.) extract towards human colorectal adenocarcinoma cells line (HT-29), Pharmacogn. J., 2017, 9, 757-761. [Crossref], [Google Scholar], [Publisher]
[22] H.M. Abdallah, G.A. Mohamed, S.R.M. Ibrahim, Lansium domesticum—a fruit with multi-benefits: traditional uses, phytochemicals, nutritional value, and bioactivities, Nutrients, 2022, 14, 1531. [Crossref], [Google Scholar], [Publisher]
[23] A.V. Lee, S. Oesterreich, N.E. Davidson, MCF-7 cells changing the course of breast cancer research and care for 45 years, J. Natl. Cancer Inst., 2015, 107, 1-4. [Crossref], [Google Scholar], [Publisher]
[24] A. Moghaddam, H.A. Zamani, H. Karimi-Maleh, A new sensing strategy for determination of tamoxifen using Fe3O4/graphene-ionic liquid nanocomposite amplified paste electrode, Chem Methodol, 2021, 5, 373-380. [Crossref], [Google Scholar], [Publisher]
[25] A. Maatta, K. Makinen, A. Ketola, T. Liimatainen, F.N. Yongabi, M. Vaha-Koskela, R. Pirinen, O. Rausti, R. Pellinen, A. Hinkkanen, J. Wahlfors, Replication competent semliki forest virus prolongs survival in experimental lung cancer, Int. J. Cancer, 2008, 123, 1704-1711. [Crossref], [Google Scholar], [Publisher]
[26] A. Amann, M. Zwierzina, G. Gamerith, M. Bitsche, J.M. Huber, G.F. Vogel, M. Blumer, S. Koeck, E.J. Pechriggl, J.M. Kelm, W. Hilbe, H. Zwierzina, Development of an innovative 3D cell culture system to study tumour – stroma interactions in non-small cell lung cancer cells, Plosone, 2014, 9, e92511. [Crossref], [Google Scholar], [Publisher]
[27] K. Fadhilah, S. Wahyuono, P. Astuti, A bioactive compound isolated from Duku (Lansium domesticum Corr) fruit peels exhibits cytotoxicity against T47D cell line, F1000Res, 2020, 9, 3. [Crossref], [Google Scholar], [Publisher]
[28] K. Fadhilah, S. Wahyuono, P. Astuti, Fractions and isolated compounds from Lansium domesticum fruit peel exhibited cytotoxic activity against T-47D and HepG2 cell lines, Biodeversitas, 2021, 22, 3743-3748. [Crossref], [Google Scholar], [Publisher]
[29] M.F. Lubis, P.A.Z. Hasibuan, H. Syahputra, J.M. Keliat, V.E. Kaban, R. Astyka, Duku (Lansium domesticum) leaves extract induces cell cycle arrest and apoptosis of HepG2 cells via PI3K/Akt pathways, Trends in Sciences, 2022, 20, 6437. [Crossref], [Google Scholar], [Publisher]
[30] M.F. Lubis, P.A.Z. Hasibuan, V.E. Kaban, R. Astyka, Phytochemicals analysis And cytotoxic activity of Lansium Domesticum corr extract-cisplatin combination against panc-1 cell line, Rasayan J Chem, 2023, 16, 32 37. [Crossref], [Google Scholar], [Publisher]
[30] M.F. Lubis, V.E. Kaban, J.O. Aritonang, D. Satria, A.A. Mulina, H. Febriani, Acute toxicity and antifungal activity of the ointment Murraya koenigii ethanol extract, Rasayan J. Chem, 2022, 15, 256-261. [Crossref], [Google Scholar], [Publisher]
[31] M.S. Fareza, N.A. Choironi, S.S. Susilowati, M.P. Rini, V. Festihawa, I.S.N. Fauzi, E.D. Utami, Sarmoko, LC-MS/MS analysis and cytotoxic activity of extract and fractions of Calophyllum soulattri stembark, Indonesian J Pharm, 2021, 32, 356-364. [Crossref], [Google Scholar], [Publisher]
[32] K.S. Sasmitaloka, S.M. Widayanti, I. Mulywanti, E.S. Iriani, Physicochemical and antioxidant characteristics of black garlic from indigenous Indonesian garlic, IOP Conf. Ser.: Earth Environ. Sci, 2022, 1041, 012004. [Crossref], [Google Scholar], [Publisher]
[33] C.K. Jiea, S. Fuloria, V. Subrimanyan, M. Sekar, K.V. Sathasivam, S. Kayarohanam, Y.S. Wu, V.S.S.R. Velaga, A.K. Janakiraman, M.N.H. Maziz, N.K. Fuloria, Phytochemical screening and antioxidant activity of Cananga odorata extract, 2022, 15, 1230-4. [Crossref], [Google Scholar], [Publisher]
[34] P.A.Z. Hasibuan, M.F. Lubis, J.M. Keliat, Cytotoxic test combination of ethyl acetate extract africant leaves (Vernonia amygdalina Delile) and gemcitabine on PANC-1 cells, AIP Conf. Proc. 2023, 2626, 030004. [Crossref], [Google Scholar], [Publisher]
[35] K. Fitri, M. Andry, T.N. Khairani, H.S. Winata, A. Violenta, N. Lubis, M.F. Lubis, Synthesis of silver nanoparticles using ethanolic extract of Nelumbo Nucifera Gaertn. leaf and its cytotoxic activity against T47D and 4T1 cell lines, Rasayan J. Chem, 2023, 16, 104-110. [Crossref], [Google Scholar], [Publisher]
[36] M.F. Lubis, H. Syahputra, D.N. Illian, V.E. Kaban, Antioxidant activity and nephroprotective effect of Lansium parasiticum leaves in doxorubicin-induced rats, J Res Pharm, 2022, 26, 565-573. [Crossref], [Google Scholar], [Publisher]
[37] I.P. Sany, Romadhon, A.S. Fahmi, Physicochemical characteristics and antioxidant activity of solid soap enriched with crude Eucheuma cottoni Extract, IOP Conf Ser: Earth Environ Sci, 2018, 246, 012066. [Crossref], [Google Scholar], [Publisher]
[38] L. Nurhidayati, Y. Fitriani, S. Abdillah, E. Mumpuni, M. Rafi, Physicochemical properties and antioxidant activities of crude fucoidan extracted from Sargassum cinereum, Indones. J. Pharm. Sci., 2020, 18, 68-74. [Crossref], [Google Scholar], [Publisher]
[39] T.S. Wahyuni, N. Khoiriyah, L. Tumewu, W. Ekasari, A. Fuad, A. Widyawaruyanti, Microscopic and physicochemical evaluation of Ruta angustifolia leaves, J. Public Health Afr., 2023, 14, 2520. [Crossref], [Google Scholar], [Publisher]
[40] V.L. Thi, N. Nguyen, Q. Nguyen, Q.V. Dong, T. Do, K.T. Nguyen, Phytochemical screening and potential antibacterial activity of defatted and nondefatted methanolic extracts of Xao Tam Phan (Paramignya trimera (Oliv.) Guillaum) peels against multidrug-resistant bacteria, Scientifica (Cairo), 2021, 34513112. [Crossref], [Google Scholar], [Publisher]
[41] R. Yuniati, M. Zainuri, H. Kusumaningrum, Qualitative tests of secondary metabolite compounds in ethanol extract of Spirulina platensis from Karimun Jawa sea, Indonesia, Biosaintifika, 2020, 12, 343-349. [Crossref], [Google Scholar], [Publisher]
[42] R. Purnama, A. Primadiamanti, Phytochemical screening, spectrum profile of functional groups, and effervescent formulation of kepok banana peels stem extract, ALKIMIA: Jurnal Ilmu Kimia dan Terapan, 2021, 4, 66-72. [Crossref], [Google Scholar], [Publisher]
[43] P. Praptiwi, D. Wulansari, A. Fathoni, N. Harnoto, R. Novita, Alfridsyah, A. Agusta, Phytochemical screening, antibacterial and antioxidant assessment of Leuconotis eugenifolia leaf extract, Nusantara Bioscience, 2020, 12, 79-85. [Crossref], [Google Scholar]
[44] A.G. Fasya, S. Amalia, D.S. Megawati, V.A. Kusuma, B. Purwantoro, Isolation, identification, and bioactivity of steroids isolates from Hydrilla verticillata petroleum ether fraction, IOP Conf Series: Earth and Enviromental Science, 2020, 456, 012009. [Crossref], [Google Scholar], [Publisher]
[45] S.A. Bhawano, O. Sulaiman, R. Hashim, M.N.M. Ibrahim, Thin-layer chromatographic analysis of steroids: a review, Trop J Pharm Res, 2010, 9, 301-313. [Crossref], [Google Scholar], [Publisher]
[46] M.F. Lubis, P.A.Z. Hasibuan, U. Harahap, D. Satria, H. Syahputra, M. Muhammad, R. Astyka, The molecular approach of natural products as pancreatic cancer treatment: a review, Rasayan J. Chem., 2022, 15, 1362-1377. [Crossref], [Google Scholar], [Publisher]
[47] S. Kamran, A. Sinniah, M.A.M. Abdulgani, M.A. Alshawsh, Therapeutic potential of certain terpenoids as anticancer agents: a scoping review, Cancers (basel), 2022, 14, 1100. [Crossref], [Google Scholar], [Publisher]
[48] H. Chen, K. Lin, A. Huang, H. Tu, B. Wei, T. Hour, M. Yen, Y. Pu, C. Lin, Terpenoids induce cell cycle arrest and apoptosis from the stems of Celastrus kusanoi associated with reactive oxygen species, J Agric Food Chem, 2010, 58, 3808-3812. [Crossref], [Google Scholar], [Publisher]
[49] Y. Liu, R.J. Whelan, B.R. Pattnaik, K. Ludwig, E. Subudhi, H. Rowland, N. Claussen, N. Zucker, S. Uppal, D.M. Kushner, M. Felder, M.S. Patankar, A. Kapur, Terpenoids from Zingiber officinale (Ginger) induce apoptosis in endometrial cancer cells through the activation of p53, Plos One, 2012, 7, e53178,. [Crossref], [Google Scholar], [Publisher]
[50] R. Mutiah, A. Widyawaruyanti, S. Sukardiman, Calotroposid A: a Glycosides Terpenoids from Calotropis gigantea induces apoptosis of colon cancer WiDr cells through cell cycle arrest G2/M and caspase 8 expression, Asian Pac. J. Cancer Prev., 2018, 19, 1457–1464. [Crossref], [Google Scholar], [Publisher]
[51] J. Fu, S. Wang, H. Lu, J. Ma, X. Ke, T. Liu, Y. Luo, In vitro inhibitory effects of terpenoids from Chloranthus multistachys on epithelial–mesenchymal transition via down-regulation of Runx2 activation in human breast cancer, Phytomedicine, 2015, 22, 165–172. [Crossref], [Google Scholar], [Publisher]
[52] H. Sun, L. Zhang, B. Sui, Y. Lo, J. Yan, P. Wang, Y. Wang, S. Liu, The effect of terpenoid natural chinese medicine molecular compound on lung cancer treatment, Evid. Based Complementary Altern. Med., 2021, 3730963. [Crossref], [Google Scholar], [Publisher]
[53] C. Bailly, G. Vergoten, Proposed mechanisms for the extracellular release of PD-L1 by the anticancer saponin platycodin D, Int. Immunopharmacol., 2020, 85, 106675. [Crossref], [Google Scholar], [Publisher]
[54] M. Rajan, G. Rajkumar, T.J.F.L. Guedes, R.G.C. Barros, N. Narain, Performance of different solvents on extraction of bioactive compounds, antioxidant and cytotoxic activities in Phoenix loureiroi Kunth leaves, J. Appl. Res. Med. Aromat. Plants, 2020, 17, 100247,. [Crossref], [Google Scholar], [Publisher]
[55] N. Armania, L.S. Yazan, S.N. Musa, I.S. Ismail, J.B. Foo, K.W. Chan, H. Noreen, A.H. Hisyam, S. Zulfahmi, M. Ismail, Dillenia suffruticosa exhibited antioxidant and cytotoxic activity through induction of apoptosis and G2/M cell cycle arrest, J. Ethnopharmacol., 2013, 146, 525–535. [Crossref], [Google Scholar], [Publisher]
[56] X. Chen, J. Shen, J. Xu, T. Herald, D. Smolensky, R. Perumal, W. Wang, Sorghum phenolic compounds are associated with cell growth inhibition through cell cycle arrest and apoptosis in human hepatocarcinoma and colorectal adenocarcinoma cells, Foods, 2021, 10, 993. [Crossref], [Google Scholar], [Publisher]
[57] P.F. Rezaei, S. Fouladdel, S. Hassani, F. Yousefbeyk, S.M. Ghaffari, G. Amin, E. Azizi, Induction of apoptosis and cell cycle arrest by pericarp polyphenol-rich extract of Baneh in human colon carcinoma HT29 cells, Food Chem. Toxicol., 2012, 50, 3-4. [Crossref], [Google Scholar], [Publisher]
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