Background: Breast cancer is the second most common cancer in women worldwide. Developing drugs increase the radiosensitivity effect of tumoral tissue, while protecting normal tissues has gained much attention. Ginsenoside Rg3, one of the active components of ginseng, has been shown to possess various pharmacological effects and antiproliferation activity on cancer cell lines. In this study, we assessed the anti-cancer effect of co-treatment with ginsenoside 20(S)-Rg3 and curcumin on MDA-MB-231 breast cancer cells with and without radiotherapy. Methods: MTT assay was applied using different concentrations of ginsenoside 20(S)-Rg3 (0, 10, 80, 150 µmol/l) and curcumin (0, 10, 30, 50, 90 µg/mL). The inhibitory effect of co-treatment with these herbal drugs with and without 4 Gy radiotherapy on the MDA-MB-231 cell line was examined. Flow cytometry was applied to measure the effect of co-treatment of the drugs on radiation-induced apoptosis. The data were analyzed using ANOVA and Kruskal-Wallis tests. P valuesResults: The results of the MTT assay showed that ginsenoside 20(S)-Rg3 and curcumin had an inhibitory effect on the MDA-MB-231 cell line in a concentration-dependent manner. Ginsenoside 20(S)-Rg3 and curcumin inhibited tumor cell development and proliferation at concentrations of 80 µmol/L and 30 μg/mL, respectively, with 50% cell viability (P=0.018, P=0.01, respectively) at 48 hour incubation time. Conclusion: Ginsenoside 20(S)-Rg3 and curcumin inhibited MDA-MB-231 cell growth in a dose- and time-dependent manner and increased the radiosensitivity of cancer cells. These herbal drugs can be considered as a radiosensitizer in radiotherapy. |
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65:5-29. doi: 10.3322/caac.21254. PubMed PMID: 25559415.
- Zhang K, Li Y. Effects of ginsenoside compound K combined with cisplatin on the proliferation, apoptosis and epithelial mesenchymal transition in MCF-7 cells of human breast cancer. Pharm Biol. 2016;54:561-8. doi: 10.3109/13880209.2015.1101142. PubMed PMID: 26511312.
- Bigdeli B, Goliaei B, Masoudi-Khoram N, Jooyan N, Nikoofar A, Rouhani M, et al. Enterolactone: A novel radiosensitizer for human breast cancer cell lines through impaired DNA repair and increased apoptosis. Toxicol Appl Pharmacol. 2016;313:180-94. doi: 10.1016/j.taap.2016.10.021. PubMed PMID: 27984132.
- Kim HG, Jang SS, Lee JS, Kim HS, Son CG. Panax ginseng Meyer prevents radiation-induced liver injury via modulation of oxidative stress and apoptosis. J Ginseng Res. 2017;41:159-68. doi: 10.1016/j.jgr.2016.02.006. PubMed PMID: 28413320; PubMed Central PMCID: PMCPMC5386123.
- Nakhjavani M, Hardingham JE, Palethorpe HM, Tomita Y, Smith E, Price TJ, et al. Ginsenoside Rg3: Potential Molecular Targets and Therapeutic Indication in Metastatic Breast Cancer. Medicines (Basel). 2019;6. doi: 10.3390/medicines6010017. PubMed PMID: 30678106; PubMed Central PMCID: PMCPMC6473622.
- Chen XJ, Zhang XJ, Shui YM, Wan JB, Gao JL. Anticancer Activities of Protopanaxadiol- and Protopanaxatriol-Type Ginsenosides and Their Metabolites. Evid Based Complement Alternat Med. 2016;2016:5738694. doi: 10.1155/2016/5738694. PubMed PMID: 27446225; PubMed Central PMCID: PMCPMC4944051.
- Mao Q, Zhang PH, Wang Q, Li SL. Ginsenoside F(2) induces apoptosis in humor gastric carcinoma cells through reactive oxygen species-mitochondria pathway and modulation of ASK-1/JNK signaling cascade in vitro and in vivo. Phytomedicine. 2014;21:515-22. doi: 10.1016/j.phymed.2013.10.013. PubMed PMID: 24252332.
- Shim SH, Baek K-H, Kim YS. Inhibition of human 20S proteasome by ginsenosides from Panax ginseng. Bulletin of the Korean Chemical Society. 2009;30:1385-7. doi: 10.5012/bkcs.2009.30.6.1385.
- Ng WY, Yang MS. Effects of ginsenosides Re and Rg3 on intracellular redox state and cell proliferation in C6 glioma cells. Chin Med. 2008;3:8. doi: 10.1186/1749-8546-3-8. PubMed PMID: 18620580; PubMed Central PMCID: PMCPMC2490693.
- Shan X, Aziz F, Tian LL, Wang XQ, Yan Q, Liu JW. Ginsenoside Rg3-induced EGFR/MAPK pathway deactivation inhibits melanoma cell proliferation by decreasing FUT4/LeY expression. Int J Oncol. 2015;46:1667-76. doi: 10.3892/ijo.2015.2886. PubMed PMID: 25672851; PubMed Central PMCID: PMCPMC6903901.
- Sin S, Kim SY, Kim SS. Chronic treatment with ginsenoside Rg3 induces Akt-dependent senescence in human glioma cells. Int J Oncol. 2012;41:1669-74. doi: 10.3892/ijo.2012.1604. PubMed PMID: 22922739.
- Lee JG, McKinney KQ, Pavlopoulos AJ, Park JH, Hwang S. Data supporting the identification of anti-metastatic drug and natural compound targets in isogenic colorectal cancer cells. Data Brief. 2014;1:73-5. doi: 10.1016/j.dib.2014.10.005. PubMed PMID: 26217691; PubMed Central PMCID: PMCPMC4459770.
- Zheng R, Deng Q, Liu Y, Zhao P. Curcumin Inhibits Gastric Carcinoma Cell Growth and Induces Apoptosis by Suppressing the Wnt/beta-Catenin Signaling Pathway. Med Sci Monit. 2017;23:163-71. doi: 10.12659/msm.902711. PubMed PMID: 28077837; PubMed Central PMCID: PMCPMC5248567.
- Mirzaei H, Shakeri A, Rashidi B, Jalili A, Banikazemi Z, Sahebkar A. Phytosomal curcumin: A review of pharmacokinetic, experimental and clinical studies. Biomed Pharmacother. 2017;85:102-12. doi: 10.1016/j.biopha.2016.11.098. PubMed PMID: 27930973.
- Wang CZ, Aung HH, Zhang B, Sun S, Li XL, He H, et al. Chemopreventive effects of heat-processed Panax quinquefolius root on human breast cancer cells. Anticancer Res. 2008;28:2545-51. PubMed PMID: 19035277; PubMed Central PMCID: PMCPMC2676904.
- Telford W, Tamul K, Bradford J. Measurement and Characterization of Apoptosis by Flow Cytometry. Curr Protoc Cytom. 2016;77:9 49 1-9 28. doi: 10.1002/cpcy.1. PubMed PMID: 27367289.
- Peng Y, Zhang R, Yang X, Zhang Z, Kang N, Bao L, et al. Ginsenoside Rg3 suppresses the proliferation of prostate cancer cell line PC3 through ROS-induced cell cycle arrest. Oncol Lett. 2019;17:1139-45. doi: 10.3892/ol.2018.9691. PubMed PMID: 30655875; PubMed Central PMCID: PMCPMC6312957.
- Kim BM, Kim DH, Park JH, Na HK, Surh YJ. Ginsenoside Rg3 Induces Apoptosis of Human Breast Cancer (MDA-MB-231) Cells. J Cancer Prev. 2013;18:177-85. doi: 10.15430/jcp.2013.18.2.177. PubMed PMID: 25337544; PubMed Central PMCID: PMCPMC4189457.
- Abuelba H, Cotrutz CE, Stoica BA, Stoica L, Olinici D, Petreus T. In vitro evaluation of curcumin effects on breast adenocarcinoma 2D and 3D cell cultures. Rom J Morphol Embryol. 2015;56:71-6. PubMed PMID: 25826489.
- Zhang F, Li M, Wu X, Hu Y, Cao Y, Wang X, et al. 20(S)-ginsenoside Rg3 promotes senescence and apoptosis in gallbladder cancer cells via the p53 pathway. Drug Des Devel Ther. 2015;9:3969-87. doi: 10.2147/DDDT.S84527. PubMed PMID: 26309394; PubMed Central PMCID: PMCPMC4539091.
- Lee YJ, Kim HY, Kang KS, Lee JG, Yokozawa T, Park JH. The chemical and hydroxyl radical scavenging activity changes of ginsenoside-Rb1 by heat processing. Bioorg Med Chem Lett. 2008;18:4515-20. doi: 10.1016/j.bmcl.2008.07.056. PubMed PMID: 18676142.
- Kim BM, Kim DH, Park JH, Surh YJ, Na HK. Ginsenoside Rg3 Inhibits Constitutive Activation of NF-kappaB Signaling in Human Breast Cancer (MDA-MB-231) Cells: ERK and Akt as Potential Upstream Targets. J Cancer Prev. 2014;19:23-30. doi: 10.15430/jcp.2014.19.1.23. PubMed PMID: 25337569; PubMed Central PMCID: PMCPMC4189477.
- Lee JG, McKinney KQ, Pavlopoulos AJ, Park JH, Hwang S. Identification of anti-metastatic drug and natural compound targets in isogenic colorectal cancer cells. J Proteomics. 2015;113:326-36. doi: 10.1016/j.jprot.2014.10.009. PubMed PMID: 25451013.
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