Combination of cisplatin, Hedyotis corymbosa L. and Tinospora crispa extracts as a new therapy for breast cancer cells 4T1 through in vitro induction and cell cycle modulation
DOI:
https://doi.org/10.12928/pharmaciana.v10i1.14060Keywords:
Cisplatin, cytotoxicity, Hedyotis corymbosa L., Tinospora crispa.Abstract
Cisplatin is a chemotherapeutic agent with varying side effects. Berberine compounds in Tinospora crispa and ursolic acids in Hedyotis corymbosa L are known to have high cytotoxic activities. This study was aimed to examine the effects of the combination of cisplatin, the ethanolic extract of Hedyotis corymbosa L.(EEHC), and the ethanolic extract of Tinospora crispa roots (EETC) on enhanced breast cancer cell sensitivity by apoptotic induction and cell cycle modulation. Cytotoxic effects were tested using the MTT assay in breast cancer cells, 4T1. The combination test of cisplatin and the extracts yielded combination index (CI) and cell viability, and its effects on the induction of apoptosis and cell cycle modulation were observed by the flow cytometry method. The results of the cytotoxic test showed CI of less than one for 1 mg/mL EEHC, 6 mg/mL EETC, and 1.68 mg/mL cisplatin. The EEHC-EETC-cisplatin combination accumulated cells in the S phase (29.98%) and induced apoptosis in 4T1 cells. It proves that EEHC and EETC can be developed as co-agents with cisplatin to improve the effectiveness of breast cancer chemotherapeutic treatment.
References
Damu, AG, Kuo, PC, Shi, LS, Li, CY, Su, CR, and Wu, TS, 2009, Cytotoxic Berberina alkaloids from the stem of Tinosporacrispa, Planta Med, 75: 1152-1156.
Donald M. Miller., Shelia D. Thomas., Ashraful Islam. David Muench and KaraSedoris., 2012, c-Myc and Cancer Metabolism, Clinical Cancer Research, 18 (20): 5546-5553.
Florea, MA, and Busselberg, D., 2011, Cisplatin as an Anti-Tumor Drug: Cellular Mechanism of Activity, Drug Resistance, and Induced Side Effect. Cancer, 3: 1351-1371.
Foo, SY, and Nolan, GP, 1999. NF-kappaB to the Rescue: reels, Apoptosis and Cellular Transformation. Trends Genet, 6: 229-235.
Foster, I., 2008, Cancer: A Cell Cycle Defect. Radiography, 14: 144-149.
Harborne, JB, 1987, Phytochemical Methods: Analyzing the Modern Way Guidance Plant. ITB Bandung, Bandung.
Holly Matthews, Jon Deakin, May Rajab, Maryam Idris-Usman, Niroshini J. Nirmalan, 2017, Investigating antimalarial drug interactions of emetine dihydrochloride hydrate using CalcuSyn-based interactivity calculations, PLoSONE, 12(3): e0173303.
IARC, 2012, Globocan 2012: Estimated Incidence of Cancer, Mortality and Prevalence Worldwide in 2012. Retrieved on August 2016.
Jamieson, ER, and Lippard, SJ, 1999, Structure, Recognition, and Processing of cisplatin DNA adducts. Chemical Reviews, 99(9): 2467-2498.
King, RJB, 2000, Cancer Biology, 2nd ed. Pearson Education Limited, London.
Kaur, P., Nagaraja, GM, Zheng, H., Gizachew, D., Galukande, M. Krishnan, S., Asea, A. 2012, A mouse model for breast cancer triple negative tumor-initiating cells (TNBCTICs) Similar exhibits aggressive phenotype to the human disease. BMC Cancer, 12:120: 1-12.
Kemper, K., Goeje, PL de, Peeper, DS, Amerongen, R. van. Phenotype 2014, Switching: Tumor Cell Plasticity as a Resistance Mechanism and Targets for Therapy. Cancer Research, 74(21): 5937-5941.
Lin, WP, Rao, H., Su Chia Sheng, KC, Shung, and Wu, T., 2002, Phenanthroindolizidine alkaloids and their cytotoxicity from the Leaves of Ficus septica. Heterocycles, 57(12): 2401-2408.
Milosavlievic, N., Duranton, C., Djerbi, N., Puech, P., Gounon, P., Lagadic Gossmann, D., et al., 2010, Effects of Cisplatin Nongenomic: Acute Inhibition of Mechanosensitive Transporters and Channels Without actin Remodeling. Molecular and Cellular Pathobiology, 70: 7514-7522.
Rollando, 2018, Combination Ofhedyotis Corymbosa L. and Tinospora Crispa Ethanolic Extract Increase Cisplatin Cytotoxicity on T47d Breast Cancer Cells, Asian Journal of Pharmaceutical and Clinical Research, 11(7): 171-177.
Minami, M., Matsumoto, S., and Horiuchi, H., 2010, Cardiovascular Side-effects of Modern Cancer Therapy, Circulation Journal, 74(9): 1779-1786.
Thangaiyan Rabbi, Anupam Bishayee, 2008, terpenoids and breast cancer chemoprevention (review). Breast Cancer Research and Treatment, 115: 223-239.
Reynolds, CP, and Maurer, BJ, 2005, Evaluating Response to Antineoplastic Drug Combinations in Tissue Culture Models, Methods in Moleculer Medicine, 110: 173-183.
Ross, J.S., Linette, G.P., Stec, J., Ross, M.S., Anwar, S., dan Boguniewics, A., 2003, DNA Ploidy and Cell Cycle Analysis in Breast Cancer, American Journal of Clinical Pathology, 120: 572–584.
MOH, 1985, Indonesian Medicinal Plants, I. Ministry of Health of the Republic of Indonesia, Jakarta.
Yoce Aprianto, Mega Asri, Hilyatul Fadliyah, Retno Murwanti, and Edy Meiyanto, 2017, antigenotoxic activity of pearl grass (Hedyotis corymbosa L.) Ethanolic extract on cyclophosphamide-induced mice, Indonesian Journal of Cancer Chemoprevention, 8(3): 127-136.
Valeriote, F., Grieshaber, CK, Media, J., Pietraszkewicz, H., Hoffmann, J., Pan, M., et al., 2002, Discovery and Development of Anticancer Agents from Plants. Journal of Experimental Therapeutics and Oncology, 2(4): 228-236.
Waqas Ahmad, Ibrahim Male, and NA Syed Bukhari, 2016, Tinospora crispa (l.) Hook. f. & Thomson: a review of its ethnobotanical, phytochemical, and pharmacological aspects, Front Pharmacol, 7(59): 1-19.
WHO, 2013, Cancer. Retrieved on August 2016.
Zhang, G., Gurtu, V., Cain, SR, and Yan, G., 1997, Early Detection of Apoptosis Using a Fluorescent Conjugate of Annexin V, BioTechnique, 23(3): 525-531.
Zhao, L., Wientjes, MG, and Au, JL, 2005. Evaluation of Combination Chemotherapy: Integration of Nonlinear Regression, Curve Shift, Isobologram, and Combination Index Analyses, Clicinal Cancer Research, 10(3): 7994-8004.
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