Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases

Abstract

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.

A review on Cyperus rotundus A potential medicinal plant

“…Furthermore, inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activatedprotein kinase (MAPK) signaling pathways failed to reverse EECR-induced apoptosis and growth inhibition. These results revealed 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 was not associated with ROS generation or the PI3K/Akt and MAPK pathways [107].…”

Phytochemical Investigation and Evaluation of in Vitro Antioxidant Activity of the Plant Cyperus Tegetum Roxb

“…The other species (Cyperus rotundus, Cyperus articulatus, and Cyperus esculentus) of Cyperaceae family are reported to have activities such as antioxidant, convulsion, and anthelmintic. The anticancer activity has been observed in the species of Cyperus rotundus [30,31]. It is reported that stigmasterol also has anticancer activity in a mouse model of 7,12-dimethylbenz(a)anthracene-induced skin carcinoma [32].…”

Novel harmine derivatives for tumor targeted therapy

“…Moreover, mitochondria mediated apoptosis is precisely regulate by Bcl-2 family proteins. Furthermore, the Bcl-2/Bax ratio is known as the ‘molecule trigger’ of apoptosis [ 35 ]. Interestingly, MET-Har-02 has insignificant influence on the ratio of Bcl-2/Bax.…”