Anticancer Activity of Typhonium flagelliforme: A Systematic Review
Abstract
Cancer is a global health issues that can affect anyone. Cancer is treated conventionally with surgery, chemotherapy, radiotherapy, and hormone therapy. However, the high cost of conventional treatments is a burden for cancer patients. Therefore, many cancer patients seek for cheaper yet effective alternative treatments. Typhonium flagelliforme is a taro-like plant that can be found across Indonesia. Numerous researches on the anticancer effect of T. flagelliformehave been conducted. However, a systematic review on the anticancer property of T. flagelliforme is still lacking. Therefore, this review aimed to systematically evaluate the scientific evidence for the anticancer activities in T. flagelliforme. Five databases were used as the search engine using the designated search terms and studies were selected based on the inclusion criteria. The anticancer evaluation in 30 studies selected were conducted in leukemia, lymphoma, breast, oral, cervical, lung, liver, colon, and squamous cell carcinoma. The result showed that T. flagelliforme could inhibit cancer cell proliferation with most of the IC50 are less than 200 μg/mL. T. flagelliformeinduced an increase of caspase-3 and -9, as well as a decrease of the anti-apoptotic Bcl-2 protein expression. The expression of p21 protein was increased after treatment of T. flagelliforme extract while the tyrosine kinase, Ki67, HER2/neu, telomerase, and COX-2 expressions were decreased implying T. flagelliforme could inhibit tumor growth and development. Lastly, T. flagelliforme is also capable in reducing the possibility of cancer cell invasion. Findings suggest that T. flagelliforme is potential to further developed for cancer treatment.
Downloads
References
Badan Penelitian dan Pengembangan Kesehatan. (2018). Laporan Nasional RISKESDAS 2018. Badan Penelitian dan Pengembangan Kesehatan Kementerian Kesehatan RI. Retrieved from http://labdata.litbang.kemkes.go.id/images/download/laporan/RKD/2018/Laporan_Nasional_RKD2018_FINAL.pdf
Brown, D. C., & Gatter, K. C. (2002). Ki67 protein: The immaculate deception? Histopathology, 40(1), 2–11. https://doi.org/10.1046/j.1365-2559.2002.01343.x
Chan, L. K., Koh, W. Y., & Tengku-Muhammad, T. S. (2005). Comparison of cytotoxic activities between in vitro and field grown plants of Typhonium flagelliforme (Lodd.) blume. Journal of Plant Biology, 48(1), 25–31. https://doi.org/10.1007/bf03030561
Chodidjah, E. D., Susanto, H., & Sarijadi. (2013). Typhonium flagelliforme decreases tyrosine kinase and Ki67 expression in mice. Universa Medicina, 32(Vol 32, No 3 (2013)), 146–154.
Chodidjah, Nasihun, T., Widayati, E., & Goenarwo, E. (2014). Typhonium flagelliforme decreases protein expression in murine breast cancer. Universa Medicina, 33(3), 163–170.
Choo, C. Y., Chan, K. L., Sam, T. W., Hitotsuyanagi, Y., & Takeya, K. (2001). The cytotoxicity and chemical constituents of the hexane fraction of Typhonium flagelliforme (Araceace). Journal of Ethnopharmacology, 77(1), 129–131. https://doi.org/10.1016/S0378-8741(01)00274-4
Choo, C. Y., Chan, K. L., Takeya, K., & Itokawa, H. (2001). Cytotoxic activity of Typhonium flagelliforme (Araceae). Phytotherapy Research, 15(3), 260–262. https://doi.org/10.1002/ptr.717
Da’i, M., Fiveri, A., & Meiyanto, E. (2007). Efek Sitotoksik Ekstrak Tanaman Keladi Tikus (Typhonium Divaricatum (L.) Terhadap Sel HeLa. Jurnal Farmasi Indonesia, 3(4), 163–167.
El-deiry, W. S., Tokino, T., Velculescu, V. E., Levy, D. B., Parsons, R., Trent, J. M., … Vogelstein, B. (1993). WAF1, a potential mediator of p53 tumor suppression. Cell, 75, 817–825.
Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicologic Pathology, 35(4), 495–516. https://doi.org/10.1080/01926230701320337
Farida, Y., Martati, T., Musir, A., & Edward, B. (2010). Uji Aktivitas Sitotoksik dan Antioksidan Ekstrak Daun Keladi Tikus (Typhonium divaricatum (L) Decne). Jurnal Ilmu Kefarmasian Indonesia, 8(2), 118–124.
Fauzi, A. N., Norazmi, M. N., & Yaacob, N. S. (2011). Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food and Chemical Toxicology, 49(4), 871–878. https://doi.org/10.1016/j.fct.2010.12.010
Geran, R. I., Greenberg, N. H., Macdonald, M. M., Shumacher, A. M., & Abbott, B. J. (1972). Protocols for screening chemical agents and natural products against animal tumors and other biological systems. In Cancer Chemotherapy Reports (Vol. Part III, pp. 1–103).
Häcker, G. (2000). The morphology of apoptosis. Cell and Tissue Research, 301(1), 5–17. https://doi.org/10.1007/s004410000193
Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: The next generation. Cell, 144(5), 646–674. https://doi.org/10.1016/j.cell.2011.02.013
Hardy, S., El-Assaad, W., Przybytkowski, E., Joly, E., Prentki, M., & Langelier, Y. (2003). Saturated fatty acid-induced apoptosis in MDA-MB-231 breast cancer cells. A role for cardiolipin. Journal of Biological Chemistry, 278(34), 31861–31870. https://doi.org/10.1074/jbc.M300190200
Harhari, K. P. Y., Supriatno, & Medawati, A. (2011). Daya Hambat Ekstrak Etanol Daun Keladi Tikus (Typhonium flagelliforme Lodd.) terhadap Proliferasi Sel Kanker Lidah Manusia (Sp-c1) secara In Vitro The Inhibition of Ethanolic Extract of Typhonium flagelliforme Lodd. Leaves toward Cell Proliferation of Hum. Mutiara Medika, 11(1), 14–18.
Harper, J. W., Adami, G. R., Wei, N., Keyomarsi, K., & Elledge, S. J. (1993). The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell, 75(4), 805–816. https://doi.org/10.1016/0092-8674(93)90499-G
Hasanah, S. N., & Widowati, L. (2016). Jamu Pada Pasien Tumor/Kanker sebagai Terapi Komplementer. Jurnal Kefarmasian Indonesia, 6(1), 49–59. https://doi.org/10.22435/jki.v6i1.5469.49-59
Kai, F. B., Drain, A. P., & Weaver, V. M. (2019). The Extracellular Matrix Modulates the Metastatic Journey. Developmental Cell, 49(3), 332–346. https://doi.org/10.1016/j.devcel.2019.03.026
Kerr, J. F. R., Wyllie, A. H., & Currie, A. R. (1972). Apoptosis: A basic biological phenomenon with wide-ranging implications in human disease. British Journal of Cancer, 26, 239–256. https://doi.org/10.1111/j.1365-2796.2005.01570.x
Kimman, M., Jan, S., Yip, C. H., Thabrany, H., Peters, S. A., Bhoo-Pathy, N., … Hung, N. C. (2015). Catastrophic health expenditure and 12-month mortality associated with cancer in Southeast Asia: Results from a longitudinal study in eight countries. BMC Medicine, 13(1), 1–11. https://doi.org/10.1186/s12916-015-0433-1
Lai, C. S., Mas, R. H. M. H., Nair, N. K., Majid, M. I. A., Mansor, S. M., & Navaratnam, V. (2008). Typhonium flagelliforme inhibits cancer cell growth in vitro and induces apoptosis: An evaluation by the bioactivity guided approach. Journal of Ethnopharmacology, 118(1), 14–20. https://doi.org/10.1016/j.jep.2008.02.034
Lai, C. S., Mas, R. H. M. H., Nair, N. K., Mansor, S. M., & Navaratnam, V. (2010). Chemical constituents and in vitro anticancer activity of Typhonium flagelliforme (Araceae). Journal of Ethnopharmacology, 127(2), 486–494. https://doi.org/10.1016/j.jep.2009.10.009
Martinvalet, D., Zhu, P., & Lieberman, J. (2005). Granzyme A induces caspase-independent mitochondrial damage, a required first step for apoptosis. Immunity, 22(3), 355–370. https://doi.org/10.1016/j.immuni.2005.02.004
Ménard, S., Pupa, S. M., Campiglio, M., & Tagliabue, E. (2003). Biologic and therapeutic role of HER2 in cancer. Oncogene, 22(43), 6570–6578. https://doi.org/10.1038/sj.onc.1206779
Modlin, I. M., Moss, S. F., Chung, D. C., Jensen, R. T., & Snyderwine, E. (2008). Priorities for improving the management of gastroenteropancreatic neuroendocrine tumors. Journal of the National Cancer Institute, 100(18), 1282–1289. https://doi.org/10.1093/jnci/djn275
Mohan, S., Abdul, A. B., Abdelwahab, S. I., Al-Zubairi, A. S., Aspollah Sukari, M., Abdullah, R., … Isa, N. M. (2010). Typhonium flagelliforme inhibits the proliferation of murine leukemia WEHI-3 cells in vitro and induces apoptosis in vivo. Leukemia Research, 34(11), 1483–1492. https://doi.org/10.1016/j.leukres.2010.04.023
Mohan, S., Abdul, A. B., Abdelwahab, S. I., Al-Zubairi, A. S., Sukari, M. A., Abdullah, R., … Syam, S. (2010). Typhonium flagelliforme induces apoptosis in CEMss cells via activation of caspase-9, PARP cleavage and cytochrome c release: Its activation coupled with G0/G1 phase cell cycle arrest. Journal of Ethnopharmacology, 131(3), 592–600. https://doi.org/10.1016/j.jep.2010.07.043
Mohan, S., Bustamam, A., Ibrahim, S., Al-Zubairi, A. S., & Aspollah, M. (2008). Anticancerous Effect of Typhonium flagelliforme on Human T4-Lymphoblastoid Cell Line CEM-ss. Journal of Pharmacology and Toxicology, 3(6), 449–456.
Mohan, S., Bustamam, A., Ibrahim, S., Al-Zubairi, A. S., Aspollah, M., Abdullah, R., & Elhassan, M. M. (2011). In vitro ultramorphological assessment of apoptosis on CEMss induced by linoleic acid-rich fraction from Typhonium flagelliforme tuber. Evidence-Based Complementary and Alternative Medicine, 2011. https://doi.org/10.1093/ecam/neq010
Nasir, N. A. K., & Bohari, S. P. M. (2015). Cytotoxicity effects of typhonium flagelliforme and clinacanthus nutans on breast cancer cells. Jurnal Teknologi, 77(31), 45–50. https://doi.org/10.11113/jt.v77.6902
Nobakht, G. M., Kadir, M. A., Stanslas, J., & Charng, C. W. (2014). Cytotoxic effect of Typhonium flagelliforme extract. Journal of Medicinal Plants Research, 8(31), 1021–1024. https://doi.org/10.5897/jmpr11.915
Norbury, C. J., & Hickson, I. D. (2001). Cellular responses to DNA damage. Annual Reviews of Pharmacology and Toxicology, 41, 367–401.
Nurrochmad, A., Lukitaningsih, E., & Meiyanto, E. (2011). Anti cancer activity of rodent tuber (Thyphonium flagelliforme (Iodd.) Blume on human breast cancer t47d cells. International Journal of Phytomedicine, 3, 138–146. Retrieved from http://ccrc.farmasi.ugm.ac.id/wp-content/uploads/63889703.pdf
Ouellette, M. M., Wright, W. E., & Shay, J. W. (2011). Targeting telomerase-expressing cancer cells. Journal of Cellular and Molecular Medicine, 15(7), 1433–1442. https://doi.org/10.1111/j.1582-4934.2011.01279.x
Paul, M. K., & Mukhopadhyay, A. K. (2012). Tyrosine kinase – Role and significance in Cancer. International Journal of Medical Sciences, 1(283), 101–115. https://doi.org/10.7150/ijms.1.101
Priosoeryanto, B. P., Rostantinata, R., Harlina, E., Nurcholis, W., Ridho, R., & Sutardi, L. N. (2020). In vitro antiproliferation activity of Typhonium flagelliforme leaves ethanol extract and its combination with canine interferons on several tumor-derived cell lines. Veterinary World, 13(5), 931–939. https://doi.org/10.14202/vetworld.2020.931-939
Purwaningsih, E., Suciati, Y., & Widayanti, E. (2016). Typhonium flagelliforme decreases telomerase expression in HeLa cervical cancer cells. Universa Medicina, 35(1), 3. https://doi.org/10.18051/univmed.2016.v35.3-9
Purwaningsih, E., Suciati, Y., & Widayanti, E. (2017). Anticancer Effect of a Typhonium flagelliforme L. in Raji Cells Through Telomerase Expression. Indonesian Journal of Cancer Chemoprevention, 8(1), 15. https://doi.org/10.14499/indonesianjcanchemoprev8iss1pp15-20
Purwaningsih, E., Widayanti, E., & Suciati, Y. (2014). Cytotoxicity assay of Typhonium flagelliforme Lodd against breast and cervical cancer cells. Universa Medicina, 33(2), 75–82. Retrieved from https://univmed.org/ejurnal/index.php/medicina/article/download/7/6
Puspitasari, L., Swastini, D. A., & Arisanti, C. I. A. (2013). Skrining Fitokimia Ekstrak Etanol 95% Kulit Buah Manggis (Garcinia mangostana L .). Jurnal Farmasi Udayana, 1(2), 15–22.
Putra, A., Tjahjono, & Winarto. (2011). Ekstrak Keladi Tikus (Typhonium flagelliforme) Fraksi Diklorometanolik dan Ekspresi Caspase-3 dan p21 Cell-Line Kanker Payudara MCF-7. Media Medika Indonesiana, 45(2), 95–104.
Putra, A., Tjahyono, & Winarto. (2012). Efektivitas Ekstrak Umbi Typhonium flagelliforme Fraksi Diklorometanolik dalam Menghambat Proliferasi Sel MCF-7 Kanker Payudara. Journal Indonesia Medical Association, 62(1), 5–10.
Ridlo, H. R., Supriatno, Medawati, A., & Rahmawati, A. D. (2012). Potensi Ekstrak Etanol Daun Keladi Tikus (Typhonium flagelliforme Lodd.) Sebagai Induktor Apoptosis Sel Kanker Lidah Manusia (SP-C1). IDJ, 1(2), 80–84. Retrieved from https://journal.umy.ac.id/index.php/di/article/view/530
Rostantinata, R., Priosoeryanto, B. P., Harlina, E., Nurcholis, W., Noviyanti, L., & Ridho, R. (2018). Antiproliferation Activity of Keladi Tikus (Typhonium Flagelliforme) Leaves Ethanol Extract on MCA- B1 and MCM-B2 Tumor-Derived Cell Lines in Vitro. In The 20th FAVA Congress & the 15th IVMA Veterinary Scientific Conference (KIVNAS) (pp. 144–145). Retrieved from http://journal.ipb.ac.id/index.php/hemera/article/view/24019
Schneider, K., Schwarz, M., Burkholder, I., Kopp-Schneider, A., Edler, L., Kinsner-Ovaskainen, A., … Hoffmann, S. (2009). “ToxRTool”, a new tool to assess the reliability of toxicological data. Toxicology Letters, 189(2), 138–144. https://doi.org/10.1016/j.toxlet.2009.05.013
Setiawati, A., Immanuel, H., & Utami, M. T. (2016). The inhibition of Typhonium flagelliforme Lodd. Blume leaf extract on COX-2 expression of WiDr colon cancer cells. Asian Pacific Journal of Tropical Biomedicine, 6(3), 251–255. https://doi.org/10.1016/j.apjtb.2015.12.012
Shen, K. C., Heng, H., Wang, Y., Lu, S., Liu, G., Deng, C. X., … Wang, Y. A. (2005). ATM and p21 cooperate to suppress aneuploidy and subsequent tumor development. Cancer Research, 65(19), 8747–8753. https://doi.org/10.1158/0008-5472.CAN-05-1471
Sianipar, N. F., Assidqi, K., Purnamaningsih, R., & Herlina, T. (2019). in Vitro Cytotoxic Activity of Rodent Tuber Mutant Plant (Typhonium Flagelliforme Lodd.) Against To Mcf-7 Breast Cancer Cell Line. Asian Journal of Pharmaceutical and Clinical Research, 12(3), 185–189. https://doi.org/10.22159/ajpcr.2019.v12i3.29651
Sobolewski, C., Cerella, C., Dicato, M., Ghibelli, L., & Diederich, M. (2010). The role of cyclooxygenase-2 in cell proliferation and cell death in human malignancies. International Journal of Cell Biology, 1–21. https://doi.org/10.1155/2010/215158
Stewart, B. W., & Wild, C. P. (2014). World Cancer Report 2014.
Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3), 209–249. https://doi.org/10.3322/caac.21660
Syahid, S. F., & Kristina, N. N. (2007). Induksi dan regenerasi kalus keladi tikus. Jurnal Littri, 13(4), 142–146.
Tietbohl, L. A. C., Oliveira, A. P., Esteves, R. S., Albuquerque, R. D. D. G., Folly, D., Machado, F. P., … Rocha, L. (2017). Antiproliferative activity in tumor cell lines, antioxidant capacity and total phenolic, flavonoid and tannin contents of Myrciaria floribunda. Anais Da Academia Brasileira de Ciencias, 89(2), 1111–1120. https://doi.org/10.1590/0001-3765201720160461
Widowati, L., & Mudahar, H. (2009). Uji Aktivitas Ekstrak Etanol 50% Umbi Keladi Tikus (Typhoniumflagelliforme (Lood) Bi) Terhadap Sel Kanker Payudara MCF-7 In Vitro. Media Litbang Kesehatan, XIX(1), 9–14.
Widyawati, P. S., Budianta, T. D. W., Kusuma, F. A., & Wijaya, E. L. (2014). Difference of solvent polarity to phytochemical content and antioxidant activity of Pluchea indicia less leaves extracts. International Journal of Pharmacognosy and Phytochemical Research, 6(4), 850–855.
World Health Organisation. (2008). Cancer control: Knowledge into action: WHO guide for effective programmes: Diagnosis and Treatment. WHO Guide for Effective Programmes, 1–42.
World Health Organization. (2020). Cancer Incident in Indonesia. International Agency for Research on Cancer, 858, 1–2.
Zakiyana, Y., Supriatno, & Medawati, A. (2010). Efek ekstrak etanol daun keladi tikus (Typhonium flagelliforme Lodd.) pada invasi sel kanker lidah manusia ( SP-C1 ) in vitro. Mutiara Medika, 10(2), 160–166.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Articles published in Indonesian Journal Life of Sciences are licensed under a Creative Commons Attribution-ShareAlike 4.0 International license. You are free to copy, transform, or redistribute articles for any lawful purpose in any medium, provided you give appropriate credit to the original author(s) and Indonesian Journal Life of Sciences, link to the license, indicate if changes were made, and redistribute any derivative work under the same license. Copyright on articles is retained by the respective author(s), without restrictions. A non-exclusive license is granted to Indonesian Journal Life of Sciences to publish the article and identify itself as its original publisher, along with the commercial right to include the article in a hardcopy issue for sale to libraries and individuals. By publishing in Indonesian Journal Life of Sciences, authors grant any third party the right to use their article to the extent provided by the Creative Commons Attribution-ShareAlike 4.0 International license.