Abstract
Breast cancer is a malignant cancer with annually increasing incidence and mortality rates. The anticancer effect of Curcuma zedoaria (Berg.) Roscoe ethanol extract (ECz) on T47D breast cancer cells was investigated in vitro. The ECz contains phenolic and flavonoid compounds that may play a critical role in anticancer activity. The viability of the treated T47D cells was significantly reduced compared to that of the control after treatment with ECz. The extract was able to induce apoptosis, upregulate B-cell lymphoma 2 (Bcl-2)-associated X protein (Bax), caspase-9, and caspase-3 protein expression levels, followed by a decrease in Bcl-2 levels and loss of mitochondrial membrane potential. In addition, the ECz also inhibited colony formation and cell migration. Signaling pathway analysis confirmed that ECz decreased the phosphorylated p38 mitogen-activated protein kinase levels. Taken together, the data suggest that ECz might be beneficial as a therapeutic agent for breast cancer.
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References
Al-Amin M, Eltayeb NM, Khairuddean M, Salhimi SM (2021) Bioactive chemical constituents from Curcuma Caesia Roxb. rhizomes and inhibitory effect of Curcuzederone on the migration of triple-negative breast cancer cell line MDA-MB-231. Nat Prod Res 35(18):3166–3170. https://doi.org/10.1080/14786419.2019.1690489
Aglund K, Rauvala M, Puistola U, Ångström T, Turpeenniemi-Hujanen T, Zackrisson B, Stendahl U (2004) Gelatinases a and B (MMP-2 and MMP-9) in endometrial cancer—MMP-9 correlates to the grade and the stage. Gynecol Oncol 94(3):699–704. https://doi.org/10.1016/j.ygyno.2004.06.028
Assays CB, Cycle C, Proliferation C, Death C, Assays CB, Cycle C, Proliferation C et al (2016) Detection of apoptosis using the BD Annexin V FITC assay on the BD FACSVerse™ system. BD Biosci 8(August):1–2
Barbieri RL (2019) Breast. In: Yen & Jaffe’s reproductive endocrinology: physiology, pathophysiology, and clinical management, 8th edn. Elsevier Inc., pp 248–255.e3. https://doi.org/10.1016/B978-0-323-47912-7.00010-X
Carson CF, Hammer KA (2011) Chemistry and bioactivity of essential Oils. In: Thormar H (ed) Lipids and essential oils as antimicrobial agents. Wiley. https://doi.org/10.1002/9780470976623.ch9
Chatatikun M (2013) Phytochemical screening and free radical scavenging activities of orange baby carrot and carrot (Daucus Carota Linn.) root crude extracts anti-melanogenic effect view project. J Chem Pharm Res. https://www.researchgate.net/publication/285964701
Chen CC, Chen Y, Hsi YT, Chang CS, Huang LF, Ho CT, Der Way T, Kao JY (2013) Chemical constituents and anticancer activity of Curcuma zedoaria Roscoe essential oil against non-small cell lung carcinoma cells in vitro and in vivo. J Agric Food Chem 61(47):11418–11427. https://doi.org/10.1021/jf4026184
Chun J, Kim YS (2013) Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways. Chem Biol Interact 205(3):212–221. https://doi.org/10.1016/j.cbi.2013.07.002
DeSantis CE, Bray F, Ferlay J, Lortet-Tieulent J, Anderson BO, Jemal A (2015) International variation in female breast cancer incidence and mortality rates. Cancer Epidemiol Biomark Prev 24(10):1495–1506. https://doi.org/10.1158/1055-9965.EPI-15-0535
Fitriana N, Rifa’I M, Widodo (2020) Curcuma zedoaria: potential effect as breast cancer chemotherapeutic agents through CXCR4 inhibition. In: AIP conference proceedings, vol 2231. American Institute of Physics Inc. https://doi.org/10.1063/5.0002629
Gao XF, Li QL, Li HL, Zhang HY, Jian Ying Su, Wang B, Liu P, Zhang AQ (2014) Extracts from Curcuma zedoaria inhibit proliferation of human breast cancer cell MDA-MB-231 in vitro. Evid Based Complement Altern Med. https://doi.org/10.1155/2014/730678
Ginsburg O, Yip CH, Brooks A, Cabanes A, Caleffi M, Yataco JAD, Gyawali B et al (2020) Breast cancer early detection: a phased approach to implementation. Cancer 126(May):2379–2393. https://doi.org/10.1002/cncr.32887
Hadisaputri YE, Miyazaki T, Suzuki S, Kubo N, Zuhrotun A, Yokobori T, Abdulah R, Yazawa S, Kuwano H (2015) Molecular characterization of antitumor effects of the rhizome extract from Curcuma zedoaria on human esophageal carcinoma cells. Int J Oncol 47(6):2255–2263. https://doi.org/10.3892/ijo.2015.3199
Halimah E, Diantini A, Destiani DP, Pradipta IS, Sastramihardja HS, Lestari K, Subarnas A, Abdulah R, Koyama H (2015) Induction of caspase cascade pathway by Kaempferol-3-O-Rhamnoside in LNCaP prostate cancer cell lines. Biomed Rep 3(1):115–117. https://doi.org/10.3892/br.2014.385
Hashim I (2015) Principles and practice of cancer prevention and control Redhwan Ahmed Al-Naggar cervical cancer: prevention and Control. (December), pp 1–12
Hudaya I, Nasihun T, Sumarawati T (2016) Effect of white turmeric extract (Curcuma zedoaria) using zam-zam solvent compare with ethanol solvent against breast cancer cell T47D. Sains Med 6(2):52. https://doi.org/10.26532/sainsmed.v6i2.601
Hsia T-C, Peng S-F, Chueh F-S, Kung-Wen Lu, Yang J-L, Huang A-C, Hsu F-T, Rick Sai-Chuen Wu (2022) Bisdemethoxycurcumin induces cell apoptosis and inhibits human brain glioblastoma GBM 8401/Luc2 cell xenograft tumor in subcutaneous nude mice in vivo. Int J Mol Sci 23(1):538. https://doi.org/10.3390/ijms23010538
Jiang Y, Tang X, Zhou B, Sun T, Chen H, Zhao X, Wang Y (2017) The ROS-mediated pathway coupled with the MAPK-P38 signalling pathway and antioxidant system plays roles in the responses of Mytilus edulis haemocytes induced by BDE-47. Aquat Toxicol 187:55–63. https://doi.org/10.1016/j.aquatox.2017.03.011
Jing L, Ma H, Fan P, Gao R, Jia Z (2015) Antioxidant potential, total phenolic and total flavonoid contents of rhododendron anthopogonoides and its protective effect on hypoxia-induced injury in PC12 cells. BMC Complement Altern Med. https://doi.org/10.1186/s12906-015-0820-3
Jung EB, Trinh TA, Lee TK, Yamabe N, Kang KS, Song JH, Choi S et al (2018) Curcuzedoalide contributes to the cytotoxicity of Curcuma zedoaria rhizomes against human gastric cancer AGS cells through induction of apoptosis. J Ethnopharmacol 213(March):48–55. https://doi.org/10.1016/j.jep.2017.10.025
Kalid M, Jahanshiri F, Omar AR, Yusoff K (2010) Gene expression profiling in apoptotic MCF-7 cells infected with newcastle disease virus. 8
Lakshmi S, Padmaja G, Remani P (2011) Antitumour effects of isocurcumenol isolated from Curcuma zedoaria rhizomes on human and murine cancer cells. Int J Med Chem 2011(March):1–13. https://doi.org/10.1155/2011/253962
Lei JC, Jian Qing Yu, Yin Y, Liu YW, Zou GL (2012) Alantolactone induces activation of apoptosis in human hepatoma cells. Food Chem Toxicol 50(9):3313–3319. https://doi.org/10.1016/j.fct.2012.06.014
Li X, Bin Su, Liu R, Dapeng Wu, He D (2011) Tetrandrine induces apoptosis and triggers caspase cascade in human bladder cancer cells. J Surg Res 166(1):e45–e51. https://doi.org/10.1016/j.jss.2010.10.034
Li Y, Liu B, Yang F, Yang Yu, Zeng A, Ye T, Yin W, Xie Y, Zhengyan Fu, Zhao C (2016) Lobaplatin induces BGC-823 human gastric carcinoma cell apoptosis via ROS—mitochondrial apoptotic pathway and impairs cell migration and invasion. Biomed Pharmacother 83:1239–1246. https://doi.org/10.1016/j.biopha.2016.08.053
Liao YF, Rao YK, Tzeng YM (2012) Aqueous extract of Anisomeles indica and its purified compound exerts anti-metastatic activity through inhibition of NF-ΚB/AP-1-dependent MMP-9 activation in human breast cancer MCF-7 cells. Food Chem Toxicol 50(8):2930–2936. https://doi.org/10.1016/j.fct.2012.05.033
Lobo R, Prabhu KS, Shirwaikar A, Shirwaikar A (2010) Curcuma zedoaria Rosc. (white turmeric): a review of its chemical, pharmacological and ethnomedicinal properties. J Pharm Pharmacol 61(1):13–21. https://doi.org/10.1211/jpp.61.01.0003
Looi CY, Arya A, Cheah FK, Muharram B, Leong KH, Mohamad K, Wong WF, Rai N, Mustafa MR (2013) Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L) seeds. PLoS ONE. https://doi.org/10.1371/journal.pone.0056643
Lourembam RM, Yadav AS, Kundu GC, Mazumder PB (2019) Curcuma zedoaria (Christm.) roscoe inhibits proliferation of MDA-MB231 cells via caspase-cascade apoptosis. Orient Pharm Exp Med 19(3):235–241. https://doi.org/10.1007/s13596-019-00374-0
Luo S-M, Yi-Ping Wu, Huang L-C, Huang S-M, Hueng D-Y (2021) The anti-cancer effect of four curcumin analogues on human glioma cells. Onco Targets Ther 14:4345–4359. https://doi.org/10.2147/OTT.S313961
Mahdizade F, Goliaei B, Parivar K, Nikoofar A (2019) Effect of a neoflavonoid (Dalbergin) on T47D breast cancer cell line and MRNA levels of P53, Bcl-2, and STAT3 genes. Iran Red Crescent Med J. https://doi.org/10.5812/ircmj.87175 (in Press)
Mutebi M, Anderson BO, Duggan C, Adebamowo C, Agarwal G, Ali Z, Bird P et al (2020) Breast cancer treatment: a phased approach to implementation. Cancer 126(S10):2365–2378. https://doi.org/10.1002/cncr.32910
Ning L, Ma H, Zhuyun Jiang Lu, Chen LL, Chen Q, Qi H (2016) Curcumol suppresses breast cancer cell metastasis by inhibiting MMP-9 via JNK1/2 and Akt-dependent NF-ΚB signaling pathways. Integr Cancer Ther 15(2):216–225. https://doi.org/10.1177/1534735416642865
Pal P, Prasad AK, Chakraborty M, Haldar S, Haldar PK (2015) Evaluation of anti cancer potential of methanol extract of curcuma. Asian J Pharm Clin Res 7(4):309–313
Rahman SN, Abdul S, Wahab NA, Malek SNA (2013a) In vitro morphological assessment of apoptosis induced by antiproliferative constituents from the rhizomes of Curcuma zedoaria. Evid Based Complement Altern Med 2013(257108):1–15
Rieger AM, Nelson KL, Konowalchuk JD, Barreda DR (2011) Modified annexin V/propidium iodide apoptosis assay for accurate assessment of cell death. J vis Exp 50:3–6. https://doi.org/10.3791/2597
Rosenberg M, Azevedo NF, Ivask A (2019) Propidium iodide staining underestimates viability of adherent bacterial cells. Sci Rep 9(1):1–12. https://doi.org/10.1038/s41598-019-42906-3
Seo WG, Hwang JC, Kang SK, Jin UH, Suh SJ, Moon SK, Kim CH (2005) Suppressive effect of Zedoariae rhizoma on pulmonary metastasis of B16 melanoma cells. J Ethnopharmacol 101(1–3):249–257. https://doi.org/10.1016/j.jep.2005.04.037
Shah N, Mohammad AS, Saralkar P, Sprowls SA, Vickers SD, John D, Tallman RM et al (2018) Investigational chemotherapy and novel pharmacokinetic mechanisms for the treatment of breast cancer brain metastases. Pharmacol Res 132(March):47–68. https://doi.org/10.1016/j.phrs.2018.03.021
Shah R, Rosso K, Nathanson SD (2014) Pathogenesis, prevention, diagnosis and treatment of breast cancer. World J Clin Oncol. https://doi.org/10.5306/wjco.v5.i3.283
Sharifi-Rad M, Varoni EM, Salehi B, Sharifi-Rad J, Matthews KR, Ayatollahi SA, Rigano D (2017) Plants of the genus zingiber as a source of bioactive phytochemicals: From tradition to pharmacy. Molecules 22(12):1–20. https://doi.org/10.3390/molecules22122145
Shin Y, Lee Y (2013) Cytotoxic activity from Curcuma zedoaria through mitochondrial activation on ovarian cancer cells. Toxicol Res 29(4):257–261. https://doi.org/10.5487/TR.2013.29.4.257
Stiefel P, Schmidt-Emrich S, Maniura-Weber K, Ren Q (2015) Critical aspects of using bacterial cell viability assays with the fluorophores SYTO9 and propidium iodide. BMC Microbiol. https://doi.org/10.1186/s12866-015-0376-x
Sung H, Ferlay J, Siegel RL, 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 Cancer J Clin 71(3):209–249. https://doi.org/10.3322/caac.21660
Sun D-I, Nizamutdinova IT, Kim YM, Cai XF, Lee JJ, Kang SS, Kim YS, Kang KM, Chai GY, Chang KC, Kim HJ (2008) Bisacurone inhibits adhesion of inflammatory monocytes or cancer cells to endothelial cells through down-regulation of VCAM-1 expression. Int Immunopharmacol 8(9):1272–1281. https://doi.org/10.1016/j.intimp.2008.05.006
Rahman SA, Nur S, Wahab NA, Malek SNA (2013b) In vitro morphological assessment of apoptosis induced by antiproliferative constituents from the rhizomes of Curcuma zedoaria. Evid Based Complement Altern Med. https://doi.org/10.1155/2013/257108
Wang L, Zhao Y, Qiong Wu, Guan Y, Xin Wu (2018) Therapeutic effects of β-elemene via attenuation of the Wnt/β-catenin signaling pathway in cervical cancer cells. Mol Med Rep 17(3):4299–4306. https://doi.org/10.3892/mmr.2018.8455
Wang X, Ni H, Wenping Xu, Bing Wu, Xie Te, Zhang C, Cheng J, Li Z, Tao L, Zhang Y (2021) Difenoconazole induces oxidative DNA damage and mitochondria mediated apoptosis in SH-SY5Y cells. Chemosphere 283(March):131160. https://doi.org/10.1016/j.chemosphere.2021.131160
Xiang M, Jiang H-G, Shu Y, Chen Y-J, Jin J, Zhu Y-M, Li M-Y, Jian-Nong Wu, Li J (2020) Bisdemethoxycurcumin enhances the sensitivity of non-small cell lung cancer cells to Icotinib via dual induction of autophagy and apoptosis. Int J Biol Sci 16(9):1536–1550. https://doi.org/10.7150/ijbs.40042
Zhang W, Zhang Q, Jiang Y, Li F, Xin H (2016) Effects of Ophiopogonin B on the proliferation and apoptosis of SGC-7901 human gastric cancer cells. Mol Med Rep 13(6):4981–4986. https://doi.org/10.3892/mmr.2016.5198
Zheng T, Xiao H, Shen Y, Zhang X, Jiang K, Liu Li, Peng J, Chen Y (2019) Anticancer effects of Curzerenone against drug-resistant human lung carcinoma cells are mediated via programmed cell death, loss of mitochondrial membrane potential, ROS, and blocking the ERK/MAPK and NF-ΚB signaling pathway. JBUON 24(3):907–912
Zheng YM, Amy Xiaoxu Lu, Shen JZ, Kwok AHY, Ho WS (2016) Imperatorin exhibits anticancer activities in human colon cancer cells via the caspase cascade. Oncol Rep 35(4):1995–2002. https://doi.org/10.3892/or.2016.4586
Zhou Na, Zhang Y, Zhang X, Lei Z, Ruobi Hu, Li H, Mao Y, Wang Xi, Irwin DM, Niu G, Tan H (2015) Exposure of tumor-associated macrophages to apoptotic MCF-7 cells promotes breast cancer growth and metastasis. Int J Mol Sci 16(6):11966–11982. https://doi.org/10.3390/ijms160611966
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We thank the Directorate General for Higher Education, Ministry of Education, Culture, Research, and Technology, for providing the PMDSU grant for this study.
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Fitriana, N., Rifa’i, M., Masruri et al. Anticancer effects of Curcuma zedoaria (Berg.) Roscoe ethanol extract on a human breast cancer cell line. Chem. Pap. 77, 399–411 (2023). https://doi.org/10.1007/s11696-022-02482-9
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DOI: https://doi.org/10.1007/s11696-022-02482-9