CYTOTOXIC ACTIVITY OF Anredera cordifolia LEAF EXTRACT ON HELA CELLS
Downloads
Cervical cancer is the second most frequently occurring cancer among females worldwide. Since the best strategy against cancer is to kill cancer cells without endangering normal cells, discovering a potentially selective anticancer agent from plants has become a major focus for researchers globally. A previous study on Anredera cordifolia, known as binahong in Indonesia, revealed its cytotoxic activity on HeLa cervical cancer cells with an IC₅₀ value of 75 µg/mL. However, the selectivity of the chemical agent and its molecular target was not investigated. Therefore, this study aimed to determine the selectivity of ethanolic extract of Anredera cordifolia leaf (EAC) on Vero cells and its molecular target on HeLa cells. The extract was prepared by macerating A. cordifolia leaf powder in 70% ethanol. The viability of Vero cells was assessed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while the cell cycle of HeLa cells was analyzed using flow cytometry. The molecular target of the extract was further investigated using immunocytochemical staining. The results demonstrated the selective cytotoxicity of EAC against HeLa cells compared to Vero cells, with a Selectivity Index (SI) of 17.36. The extract induced cell cycle arrest at the G1/S phase and suppressed Bcl-2 expression, an anti-apoptotic protein that also regulates cell cycle progression. These findings support the potential use of A. cordifolia leaf extract as a promising anticancer agent against cervical cancer, particularly HeLa cells.
Ahmadzadeh A, Shahbazian H, Safapour N, Tulabi M, Zandifar S. 2015. Comparison between the effects of one-day treatment regimen with cisplatin on renal function and various biochemical parameters in patients with gastric and lung cancer compared with two-day divided cisplatin treatment regimen. J Renal Inj Prev.
Bruni L, Barrionuevo-Rosas L, Albero G, Serrano B, Mena M, Gómez D, ... de Sanjosé S. 2017. ICO Information Centre on HPV and Cancer (HPV Information Centre). Human Papillomavirus and Related Diseases in the World. Summary Report, 19 May 2017.
Calderón-Arancibia J, Espinosa-Bustos C, Cattete-Molina A, Tapia RA, Faundez M, Torres NIJ, ... Salas CO. 2015. Synthesis and pharmacophore modelling of 2,6,9-trisubstituted purine derivatives and their potential role as apoptosis-inducing agents in cancer cell lines. Molecules 20:6808-26.
Di Domenico F, Foppoli C, Coccia C, Perluigi M. 2012. Antioxidants in cervical cancer: Chemopreventive and chemotherapeutic effects of polyphenols. Biochimica et Biophysica Acta — Mol Basis Disease.
Djamil R, Wahyudi PS, Wahono S, Hanafi M. 2012. Antioxidant activity of flavonoid from Anredera cordifolia (Ten.) Steenis leaves. Int Res J Pharm.
Drayton RM, Catto JW. 2012. Molecular mechanisms of cisplatin resistance in bladder cancer. Expert Rev Anticancer Ther.
Eifler A, Godoy G, Bazzo KO, De Moura LB. 2014. Expression analysis of p53, Ki–67 and bcl–2 in pre-malignant lesions of the cervix. Open J Obstet Gynecol 4:462–9.
Florea A, Büsselberg D. 2011. Cisplatin as an anti-tumor drug: cellular mechanisms of activity, drug resistance and induced side effects. Cancers 13:2315–25.
Hassan M, Watari H, Abualmaaty A, Ohba Y, Sakuragi N. 2014. Apoptosis and molecular targeting therapy in cancer. BioMed Res Int:150845.
Hong JH. 2006. Concurrent chemotherapy for cervical cancer patients primarily treated with radiotherapy: Is it necessary for all? Chang Gung Med J.
Huang H, Duan H, Huang H, Tong X, Han Y, Ru Y, Zhao Z. 2016. Cisplatin resistance in gastric cancer cells is associated with HER2 upregulation-induced epithelial-mesenchymal transition. Sci Rep 6:20502.
Hu Y, Cai ZQ, Su XY. 2012. Concurrent weekly cisplatin versus triweekly cisplatin with radiotherapy in the treatment of cervical cancer: A meta-analysis result. Asian Pacific J Cancer Prev 13(9):4301–4.
International Agency for Research on Cancer (IARC). 2013. Latest world cancer statistics. Lyon (FR): IARC.
International Agency for Research on Cancer (IARC). 2014. World cancer report 2014. Lyon (FR): IARC, WHO.
International Agency for Research on Cancer (IARC). 2014. World cancer report 2014. Lyon (FR): IARC, WHO.
International Standard ISO/EN 10993-5. 2009. Biological evaluation of medical devices — Part 5: Tests for cytotoxicity: In vitro methods. 3:42.
Jan S, Kimman M, Kingston D, Woodward M. 2012. The socioeconomic burden of cancer in member countries of the Association of Southeast Asian Nations (ASEAN): Stakeholder meeting report. Asian Pacific J Cancer Prev 13:411–20.
Koff JK, Ramachandiran S, Bernal-Mizrachi L. 2015. A time to kill: Targeting apoptosis in cancer. Int J Mol Sci 16:2942–55.
Larasati YA, Dewi D, Putri P, Utomo RY, Hermawan A, Meiyanto E. 2014. Combination of cisplatin and cinnamon essential oil inhibits HeLa cells proliferation through cell cycle arrest. J Appl Pharm Sci.
Leisching G, Loos B, Botha M, Engelbrecht AM. 2015. Bcl-2 confers survival in cisplatin-treated cervical cancer cells: Circumventing cisplatin dose-dependent toxicity and resistance. J Transl Med 13:328.
Mahavorasirikul W, Chaijaroenkul W, Itharat A, Na-Bangchang K. 2009. Screening of cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma cells in vitro. Drug Metab Rev 41:85.
Menezes C, Valério E, Dias E. 2013. The kidney Vero-E6 cell line: A suitable model to study the toxicity of microcystins. In: Gowder SJT, editor. New Insights into Toxicity and Drug Testing. London (UK): InTechOpen. p. 29–48.
Naser MH, Mahdavi M, Davoodi J, Tackallou SEI, Goudarzvand M, Neishabouri SH. 2015. Upregulation of Bax and downregulation of Bcl-2 during 3-NC mediated apoptosis in human cancer cells. Cancer Cell Int 15:55.
Prasaja Y, Sutandyo N, Andrajati R. 2015. Incidence of cisplatin-induced nephrotoxicity and associated factors among cancer patients in Indonesia. Asian Pacific Journal of Cancer Prevention.
Pendleton KP, Grandis JR. 2013. Cisplatin-based chemotherapy options for recurrent and/or metastatic squamous cell cancer of the head and neck. Clinical Medicine Insights: Therapeutics 3: 103–116.
Peng Y, Fu Z, Guo CS, Zhang YX, Di Y, Jiang B, Li QW. 2015. Effects and mechanism of baicalin on apoptosis of cervical cancer HeLa cells in-vitro. Iranian Journal of Pharmaceutical Research 14(1): 251–261.
Setiawati A. 2016. Celecoxib, a COX-2 selective inhibitor, induces cell cycle arrest at the G2/M phase in HeLa cervical cancer cells. Asian Pacific Journal of Cancer Prevention.
Tharavichitkul E, Lorvidhaya V, Kamnerdsupaphon P, Sukthornya V, Chakrabandhu S, Klunkin P, Chitapanarux I. 2016. Combined chemoradiation of cisplatin versus carboplatin in cervical carcinoma: A single institution experience from Thailand. BMC Cancer 16: 501.
Terrano DT, Upreti M, Chambers TC. 2010. Cyclin-dependent kinase 1-mediated Bcl-xL/Bcl-2 phosphorylation acts as a functional link coupling mitotic arrest and apoptosis. Molecular and Cell Biology.
Torre LA, Bray F, Siegel RL, Ferlay J, Tieulent JL, Jemal A. 2015. Global cancer statistics 2012. CA: A Cancer Journal for Clinicians 65: 87–107.
Tulay P, Serakinci N. 2016. The role of human papillomaviruses in cancer progression. Journal of Cancer Metastasis and Treatment 2: 201–213.
Weinberg RA. 2007. The Biology of Cancer. New York (US): Garland Science. 339 p.
Yuliani SH, Anggraeni CD, Sekarjati W, Panjalu P, Istyastono EP, Setiawati A. 2015. Cytotoxic activity of Anredera cordifolia leaf extract on HeLa cervical cancer cells through p53-independent pathway. Asian Journal of Pharmaceutical and Clinical Research 8(2): 328–331.
Zhang W, Zhang D, Ma X, Liu Z, Li F, Wu D. 2014. Paris saponin VII suppresses the growth of human cervical cancer HeLa cells. European Journal of Medical Research 19: 41.
Zhou XL, Wang M. 2015. Expression levels of survivin, Bcl-2, and KAI1 proteins in cervical cancer and their correlation with metastasis. Genetics and Molecular Research 14(4): 17059–17067.
Zhu J, Ji S, Hu Q, Chen Q, Liu Z, Wu J, Gu W. 2018. Concurrent weekly single cisplatin vs. tri-weekly cisplatin alone with radiotherapy for treatment of locally advanced cervical cancer: A meta-analysis. Cancer Management and Research 10: 1975–1985.
Copyright (c) 2018 BIOTROPIA - The Southeast Asian Journal of Tropical Biology

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
Authors who publish with this journal agree with the following terms:
- Authors retain copyright and grant the journal right of first publication, with the work 1 year after publication simultaneously licensed under a Creative Commons attribution-noncommerical-noderivates 4.0 International License that allows others to share, copy and redistribute the work in any medium or format, but only where the use is for non-commercial purposes and an acknowledgement of the work's authorship and initial publication in this journal is mentioned.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).




