Welcome to International Network for Natural Sciences | INNSpub

Philippine ethnobotanicals show anti-proliferative and cytotoxic activities in human breast cancer cells (MCF-7)

Research Paper | November 1, 2018

| Download 7

Edlyn E. Pooten, Glenn G. Oyong, Khristina G. Judan Cruz

Key Words:

Int. J. Biosci.13( 5), 239-251, November 2018

DOI: http://dx.doi.org/10.12692/ijb/13.5.239-251


IJB 2018 [Generate Certificate]


The increasing trend and threat of breast cancer had paved the search for novel compounds to discover drugs for its treatment.  Since the discovery and development of plant-based anti-tumor drugs, plants has been the focus of several researches to discover species with pharmacological potential. The Philippine Ilongot-Egongot ethno botanicals were tested for anti-proliferative and cytotoxic activities to determine their anticancer potential against breast adenocarcinoma (MCF-7) cancer cell line using PrestoBlue® Assay.  Nine extracts showed toxic effects on MCF-7 cells: Cestrum nocturnum, Sarcandra glabra, Oreocnide trinervis, Pittosporum pentandrum, Derris elliptica, Alstonia scholaris, Ageratina adenophora, Ayapana triplinervis and Lop-lopiit (no known scientific name), Two extracts showed anticancer activity against MCF-7 while being nontoxic to the normal cells (normal primary dermal fibroblast, neonatal (HDFn):  O. trinervis and A. triplinervis.  This preferential toxicity makes these enthnobotanicals ideal candidates for anti-cancer drug discovery and development.


Copyright © 2018
By Authors and International Network for
Natural Sciences (INNSPUB)
This article is published under the terms of the Creative
Commons Attribution Liscense 4.0

Philippine ethnobotanicals show anti-proliferative and cytotoxic activities in human breast cancer cells (MCF-7)

Abe R, Ohtani K. 2013. An ethnobotanical study of medicinal plants and traditional therapies on Batan Island, the Philippines. Journal of Ethnopharmacology 145(2), 554-65.

Alhosin M, Abusnina A, Achour M, Sharif T, Muller C. 2010. Induction of apoptosis by thymoquinone in lymphoblastic leukemia jurkat cells is mediated by a p73- dependent pathways which target the epigenetic integrator UHRF1. Biochemical Pharmacology 79, 1251-1260.

American Cancer Society. 2016. Cancer Facts and Figures 2016. Retrieved on April 20, 2017 from. www.cancer.org/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2016/cancer-facts-and

Ansarullah SJ, Bharucha B, Dwivedi M, Laddha NC, Begum R, Hardikar AA, Ramachandran AV. 2011. Antioxidant rich flavonoids from Oreocnide integrifolia enhance glucose uptake and insulin secretion and protects pancreatic β-cells from Streptozotocin. Bio Med Central Complement Alternative Medicine 11, 126.

Balunas M, Kinghorn AD. 2005. Drug discovery from medicinal plants. Life Sciences 78, 431.

Barrajon Catalan E, Fernandez-Arroyo S, Saura D, Guillen E, Fernandez Gutierrea A, Segura Carretero A,  Micol A. 2010. Cistaceae aqueous extracts containing ellagitannins show antioxidant and antimicrobial capacity and cytotoxic activity against human cancer cells. Food Chemical. Toxicology 48, 2273-2282.

Birt DF, Hendrich S, Wang W. 2001. Dietary agents in cancer prevention: flavonoids and isoflavonoids. Pharmacolology and Therapeutics 90, 157-177.

Bronikowska J, Szliska E, Kjaworska D, Czuba ZP, Krol W. 2012. The coumarin psoralidin enhances anticancer effect of Tumor Necrosis Factor- Related Apoptosis-Inducing Ligand (TRIAL). Molecules 17, 6449-6464.

Cao Ac, He L, Hou J, Wang Q, Guo M. 2009. Chinese Patent CN 101481299 A.

Charhar MKN, Sharma Joshi YC. 2011. Flavonoids: A versatile source of anticancer drugs. Pharmacognosy Reviews 5(9), 1-12.

Chen PH, Peng CY, Pai HC, Teng CM, Chen CC, Yang CR. 2011. Denbinobin suppresses breast cancer metastasis through the inhibition of Src-mediated signaling pathways. Journal of Nutritional Biochemistry 22, 732-40.

Chiu HL, Jyh- Horng W, Yu-Tang T, Lee TH, Chien SC, Kuo YH. 2008. Triterpenoids and aromatic from Derris laxiflora. Journal of Natural Products, 71(11), 1829-1832.

De Los Reyes MM, Oyong GG, Ebajo VD JR, Ng VAS, Shen CC, Ragasa CY. 2015. Cytotoxic triterpenes and sterols from Pipturus arborescens (Link). Journal of Applied Pharmaceutical Science, 5(11), 023-030.

Elisabetsky E, Costa-Campos L. 2006. The alkaloid alstonine: A review of its pharmacological properties. Journal of Evidence- based Complementary and Alternative Medicine 3(1), 39-48.

El-Najar N, Chatila M, Moudadem H, Vuorela H, Ocker M. 2010. Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis 15, 183-195.

Escobar-Sanchez ML, Sanchez-Sanchez L, Sandoval Ramirez J. 2015. Steroidal saponins and cell death in cancer, cell death Tobias Ntuli, Intech Open. http://dx.doi.org/10.5772/61438

Fabricant DS, Farnsworth NR. 2001. The value of plants used in traditional medicine for drug discovery. Environmental Health Perspectives 109, 69-75.

Fayad W, Rickardson L,  Haglund C, Olofsson MH, Arcy PD, Larsson R,  Linder S, Fryknas M. 2011. Identification of agents that induce apoptosis of multicellular tumor spheroids: Enrichment for mitotic inhibitors with hydrophobic properties. Chemical Biology Drug Design 78, 547-557.

Florento L, Matias R, Tuano E, Santiago K, Dela Cruz F, Tuazon A. 2012. Comparison of cytotoxic activity of anticancer drugs against various human tumor cell lines using in vitro cell- based approach. International Journal of Biomedical Science 8(1), 76-80.

Gomes De Melo J, Santos AG, Cavalcanti De Amorim EL, Donascimento SC, De Albuquerque UP. 2011. Medicinal plants used as antitumor agents in Brazil: An ethnobotanical approach. Journal of Evidence-Based Complementary and Alternative Medicine 365359, 1-14.

Haridas V, Nishimura G, Xu ZX, Connolly F, Hanausek M. 2009. Avicin D: A protein reactive plant isoprenoid dephosphorylates stat 3 by regulating both kinase and phosphatase activities. PloS One 4(10), 1371.

Hui-Ping W, Mu Z, Yong L, Weng-Quan L. 2014. Extraction and isolation of β-elemene from Eupatorium adenophorum. Journal of Chemical and Pharmaceutical Research 6(5), 161-165.

Jiang WZ, Kong XL, Liang G. 2001. Effects of Tabellae sarcandreae on malignant tumor and immunity. Journal Guangxi Medicine University 18, 39-41.

Judan -Cruz KG, Gatchalian JJC, Jacinto WR. 2018a. Philippine ethnobotanicals inhibit quorum sensing–controlled biofilm formation in Pseudomonas aeruginosa. International Journal of Biology, Pharmacy and Applied Sciences 7(4), 527-537.

Judan Cruz KG, Gabriel CMS, Abella EA. 2018b. Biological Activities of Philippine Ethnotoxic Plants. International Journal of Biology, Pharmacy and Applied Sciences 7(5), 709-718.

Kamarajan P, Sekar N, Mathuram V, Govindasamy S. 1991. Antitumor effect of echitamine chloride on methylcholonthrene induced fibrosarcoma in rats. Biochemistry International, 25(3), 491-498.

Kawase M. 2005. Coumarin derivatives with tumor-specific cytotoxicity and multidrug resistance reversal activity. In Vivo 19(4), 705-11.

Kessler M, Ubeaud GC, Jung L. 2003.  Antoprooxidant activity of rutin and quercetin  derivatives. Journal of Pharmacology 55(2), 131-142.

Khan IA, Rali T, Sticher O. 1993. Flavonoids and ionone-realted compounds from Oreocnide rubescens. Planta Medica 59(3), 287.

Larrosa M, Tomas-Barberan FA, Espin JC. 2006. The dietary hydrolysable tannin punicalagin releases ellagic acid that induces apoptosis in human colon adenocarcinoma Caco-2 cells by using the mitochondrial pathway. Journal of Nutritional Biochemistry 17, 611-625.

Li  QQ, Wang G, Huang F, Banda M, Reed E. 2010. Antineoplastic effect of beta-elemene on prostate cancer cells and other types of solid tumor cells. Journal of Pharmacy and Pharmacology 62, 1018-1027.

Li X, Wang G, Zhao J, Ding H, Cumingham C, Chen F, Flynn DC, Reed E, Li QQ. 2005. Antiproliferative effect of beta-elemene in chemo resistant ovarian carcinoma cells is mediated through arrest of the cell cycle at the G2-Mphase. Cellular and Molecular Life Science 62, 894-904.

Liu LF. 1989. DNA topoisomerase poisons as antitumor drugs. Annual Review of Biochemistry 58, 351-375.

Limos GBB, Judan Cruz KG, Jacinto WR. 2018. Quorum Sensing Inhibition Bioactivities of Philippine Ethnobotanicals against Pseudomonas aeruginosa. Int. J. Pure App. Biosci. 6(2), 47-56. http://dx.doi.org/10.18782/2320-7051.6338

Ma QP, Cheng CR, Li XF, Liang  XY, Ding J. 2015. Chemistry, pharmacological activities and analysis of Ageratina adenophora. Asian Journal of Chemistry 27(12), 4311-4316.

Man S, Gao W, Zhang Y, Huang L, Liu C. 2010. Chemical study and medical application of saponins as anti-cancer agents. Fitoterapia 81(7), October 2010, Pages 703-714.

Makita H, Tanaka T, Fujitsuka H, Tatematsu N, Satoh K, Hara A. 1996. Chemorprevention of 4-nitroquinoline-1-oxide-induced rat oil carcinogenesis by the dietary flavonoids chalcome, 2-hydroxychalcone, and quercetin. Cancer Research 56, 4904-9.

Meena AK, Garg N, Nain J, Meena RP, Rao MM. 2011. Review on ethnobotany, phytochemical and pharmacological profile of Alstonia scholaris. International Research Journal of Pharmacy 2(1), 49-54.

Musa MA, Cooperwood JS, Khan MOF. 2008. A Review of coumarin derivatives in pharmacotherapy of breast cancer. Current Medicinal Chemistry 15, 2664-2679.

Nainggolan M, Kasmirul. 2015. Cytotoxicity activity of male Carica papaya L. flowers on MCF-7 breast cancer cells. Journal of Chemical and Pharmaceutical Research, 2015, 7(5), 772-775.

Nasr T, Bondock S, Youns M. 2014. Anticancer activity of new coumarin substituted hydrazide-hydrazone derivatives. European Journal of Medicinal Chemistry 76, 539-548.

Nawab A, Yunus M, Manhdi AA, Gupta S. 2011. Evaluation of anticancer properties of medicinal plants from the Indian Sub-Continent. Molecular Cell Pharmacological 2011, 3(1), 21-29.

Neubig RR, Spedding M, Kenakin T, Christopoulos A. 2003. International union of pharmacology committee on receptor nomenclature and drug classification. XXXVIII. Update on terms and symbols in quantitative pharmacology. Pharmacological Reviews 55, 597–606.

Oduro I, Larbie C, Amaoako TNE, Antwi-Baoasiako AF. 2009. Proximate composition and basic phytochemical assessment of two common varieties of Terminalia catapa. Journal of Science Technology 29, 1-6.

Okwu DE, Okwu ME. 2004. Chemical composition of Spondias mombin Linn. Plant parts. Journal of Sustainable Agriculture and Environment 6(2), 140-147.

Osborne CK, Schiff R. 2011. Mechanisms of endocrine resistance in breast cancer. Annual Review of Medicine 62, 233-247.

Philippine Society of Medical Oncology. 2015. www.pchrd.dost.gov.ph.

Podolak I, Galanty A, Sobolewska D. 2010. Saponins as cytotoxic agents: a review. Photochemistry Reviews 9(3), 425-474.

Rao AV, Sung MK. 1995. Saponins as anticarcinogens. Journal of Nutrition 125, 717S-724S.

Rashed KNZ. 2013. Investigation of antioxidant activity from Cestrum nocturnum L. stems and phytochemical content. Reviews of Progress 1(5), 2321-3485.

Redaniel MTM, Laudico AV, Lumague MRM, Mapua CA, Patama T, Pukkala E. 2008.  Cancer in the Philippines. 4(1), – Cancer Incidence 1998-2002. Philippine Cancer Society.

Riveiro M. 2004. Induction of cell differentiation in human leukemia U-937 cells by 5-oxygenated-6,7- methylenedioxy coumarins from Pterocaulon polystachyum Cancer Letters, 210(1), 179-188.

Riveiro M. 2009. Toward establishing structure- activity relationships of oxygenated coumarins as differentiation inducers of promonocytic leukemic cells. Bioorganic and Medicinal Chemistry, 17(18), 6547-6559.

Sadipo OA, Akanji MA, Kolawole FB, Odutuga AA. 1991. Saponin is the active antifungal principle in Garcinia kola, Heckle seeds. Biological Scientific Research Communications 3, 163-171.

Sashidhara KV, Palnati GR, Sonkar R, Avula SR, Awasthi C, Bhatia G. 2013. Coumarin chalcone fibrates: a new structural class of lipid lowering agents. European Journal of Medicinal Chemistry 64, 422-431.

Sasidharan  S, Chen Y, Saravanan D, Sundram KM, Latha LY. 2011. Extraction, isolation and characterization of bioactive compounds from plants’ extracts. African Journal of Traditional Complementary and Alternative Medicine 8(1), 1–10.

Scio E. 2003. Diterpenes from Alomia myriadenia (Asteraceae) with cytotoxic and trypanocidal activity. Phytochemistry 64(6), 1125-1131.

Shimamura T, Zhao WH, Hu ZQ. 2007. Mechanisms of action and potential for use of tea catechin as an anti-infective agent. Anti-Infective Agents in Medicinal Chemistry 6(1), 57-62.

Srisawat U, Hunlatthanaphorn SC, Lertprasertsuke N, Thuppia A, Ngamjariyawat  A, Suwanlikhid  N, Jaijoy  K. 2007. Acute and subchronic toxicity study of the water extract from root of Citrus aurantifolia (Christm. et Panz.) shingle in rats. Songklanakarin Journal of Science Technology 1, 125-139.

Suffness M,  Pezzuto JM. 1990. Assays related to cancer drug discovery. Methods in Plant Biochemistry. Assays for Bioactivity 6, 71-133.

Surya SP, Jayanthi G, Smitha KR. 2012. In vitro evaluation of the anticancer effect of methanolic extract of Alstonia scholaris leaves on mammary carcinoma. Journal of Applied Pharmaceutical Science 2(5), 1.

Tan DX, Reiter RJ, Manchester LC. 2013. Chemical and physical properties and potential mechanisms: melatonin as a broad spectrum antioxidant and free radical scavenger. Current Topics Medicinal Chemistry 2, 181-197.

Tanaka T, Makita H, Ohnishi M, Mori H, Satoh K, Hara A. 1997. Chemoprevention of 4-nitroquinonline 1-oxide-induced oral carcinogenesis in rats by flavonoids diosmin and hesperidin, each alone and in combination. Cancer Research 57, 246-52.

Torre LA, Bray F, Siegel  RL, Lortet -Tieulent J, Jemal A. 2015. Global cancer statistics, 2012. A Cancer Journal Clinicians 65(2), 87-108.

Undan JR, Cruz KJ, Gandalera EE, Abella EA , David ES, Valentino MJG, Reyes RG. 2014. An ethnobotanical expedition of plants with pharmacological potential used by the Igorot Tribe of Imugan, Sta. Fe, Nueva Vizcaya, Philippines. Central Luzon State University, Science City of Muñoz, Nueva Ecija.

Vikas S, Mallick SA, Tiku AK. 2010. Anticancer activity of devil tree (Alstonia scholaris Linn.) leaves on human cancer cell lines. Indian Journal of Agricultural Biochemistry, 23(1), 63-65.

Wang G,  Li X, Huang  F, Zhao J, Ding H, Cunningham C, Coad JE, Flynn DC, Reed E, Li QQ. 2005. Antitumor effect of beta-elemene in non-small-cell lung cancer cells is mediated via induction of cell cycle arrest and apoptotic cell death. Cellular and Molecular Life Science 62, 881-893.

Wani MC, Taylor H, Wall ME. 1971. Plant antitumor agents VI. The isolation and structure of taxol, a novel anti leukemic and antitumor agent from Taxus brevifolia. Journal of American Chemical Society 93, 2325-2327.

Watanabe J. 2005. Coumarin and flavone derivatives from estrogen and thyme as inhibitors of chemical mediator release from RBL-2H3 cells. Biotechnology 69(1), 1-6.

Woo CC, Hsu A, Kumar AP, Sethi G, Tan KHB. 2013. Thymoquinone inhibits tumor growth and induces apoptosis in a breast cancer xenograft mouse model: The role of p38 MAPK and ROS. PloS ONE, 8(10), 753.

Xu L, Bian K, Liu Z, Zhou J, Wang  G. 2005. The inhibitory effect of the curcumol on women cancer cells and synthesis of RNA. Tumor 25, 570-572.

Yao YQ, Ding X,  Jia YC, Huang CX, Wang  YZ,  Xu YH. 2008. Anti-tumor effect of beta-elemene in glioblastoma cells depends on p38 MAPK activation. Cancer Letter 264, 127-134.

Yuan J, Gu ZL, Chou WH, Kwok CY. 1999. Elemene induces apoptosis and regulates expression of bcl-2 protein in human leukemia K562 cells. Zhongguo Yao Li Xue Bao, 20, 103-106.

Zhao W, Zhu L,  Srinivasan S,  Damodaran C, Rohr J. 2009. Identification of urushiols as the major active principle of the Siddha herbal medicine Semecarpus Lehyam: Anti-tumor agents for the treatment of breast cancer Pharmaceutical Biology 2009 Sep 1, 47(9), 886–893.

Zheng W, Wang S, Chen X, Hu Z. 2003. Analysis of Sarcandra glabra and its medicinal preparations by capillary electrophoresis. Talanta 60, 955-960.

Zhong Z, Chen X, Tan W, Xu Z, Zhou K, Wu T, Cui  L, Wang Y. 2011. Germacrone inhibits the proliferation of breast cancer cell lines by inducing cell cycle arrest and promoting apoptosis. European Journal of Pharmacology 667, 50-55.

Zhisen J, Meng Cheng T, Jianming W. 1999. The determination of flavonoid contents in mulberry and their scavenging effects on superoxide radicals. Food Chemistry 64, 555-559.

Zhu  T, Xu Y, Dong B, Zhang  J, Wei Z, Xu Y, Yao Y. 2011. Beta-elemene inhibits proliferation of human glioblastoma cells through the activation of glia maturation factor beta and induces sensitization to Cisplastin. Oncology Reports 26, 405-413.

Ziegler  HL, Dan S, Jette C, Lars H, Henry H, Jerzy WJ. 2002. In vitro plasmodium falciparum drug sensitivity assay: Inhibition of parasite growth by incorporation of stomatocytogenic amphilhiles into the erythrocyte membrane. Antimicrobial Agents and Chemotherapy 46(5), 1441-1446.

Zou L, Liu W, Yu L. 2001. Beta-elemene induces apoptosis of K562 leukemia cells. Zhong Zhong Liu Za Zhi, 23, 196-198.