The aqueous extract of Gerrardanthus macrorhizus caudex enhanced doxorubicin activity in MCF-7 human breast cancer cells

Sari Haryanti(1*), Yuli Widiyastuti(2), Slamet Wahyono(3)

(1) Medicinal Plant and Traditional Medicine Research and Development Centre Jl. Raya Lawu No. 11, Tawangmangu, Kalisoro, Karanganyar, Jawa Tengah 57792
(2) Medicinal Plant and Traditional Medicine Research and Development Centre Jl. Raya Lawu No. 11, Tawangmangu, Kalisoro, Karanganyar, Jawa Tengah 57792
(3) Medicinal Plant and Traditional Medicine Research and Development Centre Jl. Raya Lawu No. 11, Tawangmangu, Kalisoro, Karanganyar, Jawa Tengah 57792
(*) Corresponding Author


Gerrardanthus macrorhizus (GM) caudex, is traditionally used in cancer therapy by the Tetun people in Belu District, East Nusa Tenggara Province, Indonesia, where it is known as “akar batu”. This study aimed to explore the cytotoxic effects of G. macrorhizus caudex aqueous extract, as well as its combination with doxorubicin, on MCF-7 cells. Also investigated were the possible mechanisms of interaction through cell cycle progression and apoptosis induction. Single treatments of 5–320 µg/mL of the extract showed morphological alterations in MCF-7 cells, but did not show any cytotoxic effect. Combining the extract with doxorubicin resulted in a synergistic cytotoxic effect. Doxorubicin concentrations equivalent to 1/12, 1/8, and 1/5 fold of the IC50 combined with 20 µg/mL decreased viability to 48%. We then explored the combination effect of doxorubicin 0.4 µM with GM 5 and 20 µg/mL using a flow cytometer. A low concentration of the extract (5 µg/mL) combined with 0.4 µM of doxorubicin resulted in slight cell cycle modulation by G1, G2M arrested and apoptosis induction. The combination of doxorubicin and a higher concentration of the extract (20 µg/mL) did not show cell cycle modulation, and led to necrosis. Therefore, G. macrorhizus caudex at low concentrations has the potential to be developed further as a co-chemotherapeutic agent.


apoptosis; cell cycle; cytotoxic; doxorubicin; Gerrardanthus macrorhizus; MCF-7

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AbuHammad S, Zihlif M. 2013. Gene expression alterations in doxorubicin resistant MCF7 breast cancer cell line. Genomics. 101:213–220. doi:10.1016/j.ygeno.2012.11.009.

Anampa J, Makower D, Sparano JA. 2015. Progress in adjuvant chemotherapy for breast cancer: an overview. BMC Medicine. 13. doi:10.1186/s12916-015-0439-8.

Balunas MJ, Kinghorn AD. 2005. Drug discovery from medicinal plants. Life Sciences. 78:431–441. doi:10.1016/j.lfs.2005.09.012.

Chou T-C. 2010. Drug combination studies and their synergy quantification using the Chou-Talalay method. Cancer Research. 70:440–446. doi:10.1158/0008-5472.CAN-09-1947.

Deep G, Agarwal R. 2008. New combination therapies with cell-cycle agents. Current Opinion in Investigational Drugs. 9:591–604.

Dias DA, Urban S, Roessner U. 2012. A historical overview of natural products in drug discovery. Metabolites. 2:303–336. doi:10.3390/metabo2020303.

Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicologic pathology. 35:495–516. doi:10.1080/01926230701320337.

Foucquier J, Guedj M. 2015. Analysis of drug combinations: current methodological landscape. Pharmacology Research & Perspectives. 3. doi:10.1002/prp2.149.

Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell. 144:646–674. doi:10.1016/j.cell.2011.02.013.

Kamil N, Kamil S. 2015. Global cancer incidences, causes and future predictions for subcontinent region. Systematic Reviews in Pharmacy. 6:13–17.

Ko E-Y, Moon A. 2015. Natural products for chemoprevention of breast cancer. Journal of Cancer Prevention. 20:223–231. doi:10.15430/JCP.2015.20.4.223.

Lal S, Mahajan A, Chen WN, Chowbay B. 2010. Pharmacogenetics of target genes across doxorubicin disposition pathway: a review. Current Drug Metabolism. 11:115–128.

Ma X, Yu H. 2006. Global burden of cancer. The Yale Journal of Biology and Medicine. 79:85–94.

Reynolds CP, Maurer BJ. 2005. Evaluating response to antineoplastic drug combinations in tissue culture models. Methods in Molecular Medicine. 110:173–183. doi:10.1385/1-59259-869-2:173.

Riss TL, Moravec RA, Niles AL, Duellman S, Benink HA, Worzella TJ, Minor L. 2016. Cell viability assays. In: Sittampalam G, Coussens N, Brimacombe K, Grossman A, Arkin M, et al., editors. Assay guidance manual [Internet]. Bethesda (MD): Eli Lilly & Company and the National Center for Advancing Translational Sciences. [accessed 2018 Feb 1].

Schwartz GK, Shah MA. 2005. Targeting the cell cycle: a new approach to cancer therapy. Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology. 23:9408–9421. doi:10.1200/JCO.2005.01.5594.

Shah MA, Schwartz GK. 2001. Cell cycle-mediated drug resistance: an emerging concept in cancer therapy. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research. 7:2168–2181.

Tacar O, Sriamornsak P, Dass CR. 2013. Doxorubicin: an update on anticancer molecular action, toxicity and novel drug delivery systems: doxorubicin cell and molecular biological activity. Journal of Pharmacy and Pharmacology. 65:157–170. doi:10.1111/j.2042-7158.2012.01567.x.

Wang S, Konorev EA, Kotamraju S, Joseph J, Kalivendi S, Kalyanaraman B. 2004. Doxorubicin induces apoptosis in normal and tumor cells via distinctly different mechanisms. intermediacy of H(2)O(2)- and p53-dependent pathways. The Journal of Biological Chemistry. 279:25535–25543. doi:10.1074/jbc.M400944200.

Wong RS. 2011. Apoptosis in cancer: from pathogenesis to treatment. Journal of Experimental & Clinical Cancer Research. 30:87. doi:10.1186/1756-9966-30-87.

Zeichner SB, Terawaki H, Gogineni K. 2016. A review of systemic treatment in metastatic triple-negative breast cancer. Breast Cancer (Auckl). 10:25–36. doi:10.4137/BCBCR.S32783.


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