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Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases.
Oncol Rep. 2014 Dec; 32(6):2461-70.OR

Abstract

Cyperus rotundus L. belongs to the Cyperaceae family and is a well documented traditional medicinal herb. Its rhizome has been reported to possess wide spectrum pharmacological activities including anti-inflammatory and antioxidant activity. However, the cellular and molecular mechanisms of the anticancer activity have not been elucidated. In the present study, we investigated the pro-apoptotic effects of C. rotundu rhizomes in a human breast carcinoma MDA-MB-231 cell model. Treatment of MDA-MB-231 cells with an ethanol extract of C. rotundu rhizomes (EECR) and a methanol extract of C. rotundu rhizomes (MECR), but not a water extract of C. rotundu rhizomes, resulted in potent antiproliferative activity. The activity of the EECR was higher than that of the MECR and was associated with the induction of apoptosis. The induction of apoptosis by the EECR was associated with upregulation of death receptor 4 (DR4), DR5 and pro-apoptotic Bax, as well as downregulation of anti-apoptotic survivin and Bcl-2. EECR treatment also downregulated Bid expression and activated caspase-8 and -9, the respective initiator caspases of the extrinsic and intrinsic apoptotic pathways. The increase in mitochondrial membrane depolarization was correlated with activation of effector caspase-3 and cleavage of poly(ADP-ribose) polymerase, a vital substrate of activated caspase-3. Blockage of caspase activation by pretreatment with a pan-caspase inhibitor consistently inhibited apoptosis and abrogated growth inhibition in EECR-treated MDA-MB-231 cells. Although reactive oxygen species (ROS) increased following treatment with the EECR, inhibiting ROS with a ROS scavenger did not attenuate EECR-induced apoptosis. Furthermore, inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathways failed to reverse EECR-induced apoptosis and growth inhibition. These results suggest that the pro-apoptotic activity of the EECR may be regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways that is not associated with ROS generation or the PI3K/Akt and MAPK pathways.

Authors+Show Affiliations

Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.Department of Molecular Biology, College of Natural Sciences, Dongeui University, Busan 614-714, Republic of Korea.Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.Team for Scientification of Korean Medical Intervention (BK21 Plus) and Department of Herbal Pharmacology, Daegu Haany University College of Korean Medicine, Daegu 706-828, Republic of Korea.Division of Applied Life Science (BK 21 Program), Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660‑701, Republic of Korea.Department of Internal Medicine, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614-052, Republic of Korea.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25241797

Citation

Park, Sang Eun, et al. "Induction of Apoptosis in MDA-MB-231 Human Breast Carcinoma Cells With an Ethanol Extract of Cyperus Rotundus L. By Activating Caspases." Oncology Reports, vol. 32, no. 6, 2014, pp. 2461-70.
Park SE, Shin WT, Park C, et al. Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases. Oncol Rep. 2014;32(6):2461-70.
Park, S. E., Shin, W. T., Park, C., Hong, S. H., Kim, G. Y., Kim, S. O., Ryu, C. H., Hong, S. H., & Choi, Y. H. (2014). Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases. Oncology Reports, 32(6), 2461-70. https://doi.org/10.3892/or.2014.3507
Park SE, et al. Induction of Apoptosis in MDA-MB-231 Human Breast Carcinoma Cells With an Ethanol Extract of Cyperus Rotundus L. By Activating Caspases. Oncol Rep. 2014;32(6):2461-70. PubMed PMID: 25241797.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases. AU - Park,Sang Eun, AU - Shin,Won Tak, AU - Park,Cheol, AU - Hong,Su Hyun, AU - Kim,Gi-Young, AU - Kim,Sung Ok, AU - Ryu,Chung Ho, AU - Hong,Sang Hoon, AU - Choi,Yung Hyun, Y1 - 2014/09/22/ PY - 2014/05/25/received PY - 2014/08/29/accepted PY - 2014/9/23/entrez PY - 2014/9/23/pubmed PY - 2015/6/27/medline SP - 2461 EP - 70 JF - Oncology reports JO - Oncol Rep VL - 32 IS - 6 N2 - Cyperus rotundus L. belongs to the Cyperaceae family and is a well documented traditional medicinal herb. Its rhizome has been reported to possess wide spectrum pharmacological activities including anti-inflammatory and antioxidant activity. However, the cellular and molecular mechanisms of the anticancer activity have not been elucidated. In the present study, we investigated the pro-apoptotic effects of C. rotundu rhizomes in a human breast carcinoma MDA-MB-231 cell model. Treatment of MDA-MB-231 cells with an ethanol extract of C. rotundu rhizomes (EECR) and a methanol extract of C. rotundu rhizomes (MECR), but not a water extract of C. rotundu rhizomes, resulted in potent antiproliferative activity. The activity of the EECR was higher than that of the MECR and was associated with the induction of apoptosis. The induction of apoptosis by the EECR was associated with upregulation of death receptor 4 (DR4), DR5 and pro-apoptotic Bax, as well as downregulation of anti-apoptotic survivin and Bcl-2. EECR treatment also downregulated Bid expression and activated caspase-8 and -9, the respective initiator caspases of the extrinsic and intrinsic apoptotic pathways. The increase in mitochondrial membrane depolarization was correlated with activation of effector caspase-3 and cleavage of poly(ADP-ribose) polymerase, a vital substrate of activated caspase-3. Blockage of caspase activation by pretreatment with a pan-caspase inhibitor consistently inhibited apoptosis and abrogated growth inhibition in EECR-treated MDA-MB-231 cells. Although reactive oxygen species (ROS) increased following treatment with the EECR, inhibiting ROS with a ROS scavenger did not attenuate EECR-induced apoptosis. Furthermore, inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathways failed to reverse EECR-induced apoptosis and growth inhibition. These results suggest that the pro-apoptotic activity of the EECR may be regulated by a caspase-dependent cascade through activation of both intrinsic and extrinsic signaling pathways that is not associated with ROS generation or the PI3K/Akt and MAPK pathways. SN - 1791-2431 UR - https://www.unboundmedicine.com/medline/citation/25241797/Induction_of_apoptosis_in_MDA_MB_231_human_breast_carcinoma_cells_with_an_ethanol_extract_of_Cyperus_rotundus_L__by_activating_caspases_ L2 - http://www.spandidos-publications.com/or/32/6/2461 DB - PRIME DP - Unbound Medicine ER -