1-oxoeudesm-11(13)-ene-12,8α-lactone-induced apoptosis via ROS generation and mitochondria activation in MCF-7 cells

Abstract

A novel eudesmane-type sesquiterpene compound, 1-oxoeudesm-11(13)-eno-12,8a-lactone (OEL), was isolated from Aster himalaicus. Its effect on apoptosis in human breast adenocarcinoma (MCF-7) cells was investigated. MTT assay showed that OEL substantially reduced the viability of KB, MCF-7, U87, A172, and MG-63 cells. MCF-7 cells were used to further evaluate the antitumor effects and anticancer mechanisms of OEL. OEL-induced apoptosis was characterized by chromatin condensation, formation of apoptotic bodies, and phosphatidylserine on extracellular surface; these effects were confirmed by DAPI nuclear staining and flow cytometry. Increased expression of Bax and deceased expression of Bcl-2 were also observed in OEL-treated MCF-7 cells. Moreover, OEL induced the loss of mitochondria membrane potential, release of cytochrome C, activation of caspase-9, and generation of reactive oxygen species. These findings indicate that reactive oxygen species generation and mitochondria activation were involved in apoptosis induced by OEL in MCF-7 cells. The results from our study demonstrated that OEL may be a promising pro-apoptotic compound that could be used to develop novel anticancer drugs.

Aqueous Extract of Sea Squirt (Halocynthia roretzi) with Potent Activity against Human Cancer Cells Acts Synergistically with Doxorubicin

“…Higher concentrations of ROS is toxic for tumor cells and induces cell apoptosis [ 19 ]. Figure 5 A,B showed that ROS generation was significantly enhanced after treatment with 200 µg/mL WB-H-S1 for 24 h. Previous studies showed that ROS generation was closely related to potential changes in the mitochondrial membrane (MMP) [ 20 ]. The intrinsic mitochondrial pathway of apoptosis is regulated by MMP.…”

Ehrlichia type IV secretion effector ECH0825 is translocated to mitochondria and curbs ROS and apoptosis by upregulating host MnSOD

“…In mitochondria, the action of MnSOD and the glutathione/glutathione peroxidase‐1 system act cooperatively to constrain the levels of ROS (mainly O 2 ‐ and H 2 O 2 ) generated during normal aerobic metabolism (Oberley and Oberley, 1988; Knirsch and Clerch, 2001; Zelko et al ., 2002). When cellular antioxidant defence systems cannot remove excess ROS, oxidative stress ensues, resulting in cell damage and apoptosis (Cai and Jones, 1998; Parone et al ., 2003; Cui et al ., 2011). Loss of MnSOD ( Sod 2 −/− ) is lethal in mice, whereas partial deficiency ( Sod 2 +/− ) increases the rate of apoptosis (Kokoszka et al ., 2001; Van Remmen et al ., 2001).…”

Telekin Induces Apoptosis Associated with the Mitochondria-Mediated Pathway in Human Hepatocellular Carcinoma Cells

“…Telekin Induced the Activation of Caspase-9 and Caspase- 3 Western blot was used to analyze whether caspase activation is involved in the mitochondria-mediated pathway in the telekin-induced apoptosis of HepG-2 cells. After the cells were treated with 2.5 to 10 µmol/L telekin for 48 h, Apaf-1, pro-caspase-9, and pro-caspase-3 in HepG-2 cells highly decreased.…”

“…A number of anticancer drugs derived from natural products, such as taxane, vinca alkaloid, and hydroxyl-camptothecin, have exhibited excellent anticancer potential. 3) Telekin is isolated from Carpesium divaricatum, which has long been used as Chinese folk medicine given its antipyretic, analgesic, vermifugic, and anti-inflammatory properties. 4) In China, the whole C. divaricatum plant is used in medicine as febrifuge and astringent.…”