Methyl jasmonate decreases membrane fluidity and induces apoptosis through tumor necrosis factor receptor 1 in breast cancer cells

Abstract

In recent years, studies with plant compounds have shown both chemotherapeutic and chemopreventive properties. The current study with plant stress hormones (jasmonates) showed growth inhibitory effects in breast cancer cells. Cis-jasmone (CJ) and methyl jasmonate (MJ) inhibited the long-term proliferation of MDA-MB-435 and MCF-7 cells. Cell cycle analysis showed G0/G1 and S-phase arrest with increasing apoptotic population. Cellular signaling studies with MJ showed decreased membrane fluidity and activation of extrinsic and intrinsic apoptotic pathways. Specifically in extrinsic apoptotic pathway increased expression of TNFR1, activation of MAPK and caspase-8 was observed. MJ also decreased the mitochondrial membrane potential and activated caspase-3 in breast cancer cells. In conclusion our results revealed novel signaling mechanism of MJ in breast cancer cells, indicating that MJ could have potential applications for chemotherapeutic purposes.

MCF-7 breast carcinoma cells do not express caspase-3

“…Curiously, several reports still claim the presence of caspase-3 in the breast carcinoma cell line MCF-7 in which this enzyme is supposed to contribute to apoptosis signaling [7][8][9][10][11][12][13][14][15]. This was not only demonstrated indirectly via fluorometric assay systems measuring caspase-3-like activities-that might be also elicited by the closely related caspase-7-but by Western blotting analyses demonstrating directly the presence of this protease in MCF-7 cells.…”

“…Thus, it is puzzling that caspase-3-deficient MCF-7 cells exhibit DNA fragmentation and other apoptotic characteristics following cell death induction as described [7][8][9][10][11][12][13][14][15]. While it is still possible that caspase-3-deficient MCF-7 cells display high molecular weight DNA fragmentation that might be occasionally mistaken for the typical apoptotic DNA fragmentation, the detection of a caspase-3 protein in MCF-7 cells [7,8,11,[13][14][15] with a partially deleted CASP-3 gene is cause for concern. Such discrepant findings may be partially explained by the use of inappropriate antibodies that cross-react with other caspase-3-unrelated proteins in cellular extracts, a phenomenon we have also observed previously (unpublished data).…”

Development and characterization of biocompatible isotropic and anisotropic oil-in-water colloidal dispersions as a new delivery system for methyl dihydrojasmonate antitumor drug

“…11 Several reports have demonstrated that cyclopentenone moiety-containing molecules such as prostaglandins and clavulones induce apoptosis in different signaling mechanisms. [12][13][14] Jasmonate-derivative compounds, including jasmonic acid (JA) and methyl dihydrojasmonate (MJ), have been reported to inhibit the growth of leukemia cells as well as lung, breast, and prostate cancer cells, and to produce in vivo anticancer activity. 15,16 Different mechanisms have been proposed to explain the anticancer activity of jasmonate derivatives.…”

Apoptotic activity of a new jasmonate analogue is associated with its induction of DNA damage

“…It has been reported that methyl jasmonate inhibits cell proliferation and induces cell death in various human and mouse cancer cell lines, such as breast, prostate, lung, melanoma, lymphoblastic leukemia and lymphoma cells (1)(2)(3). Methyl jasmonate exhibited selective cytotoxicity to transformed cells while sparing normal blood lymphocytes, even when the latter were part of a mixed population of leukemic and normal cells drawn from the blood of chronic lymphocytic leukemia (CLL) patients (4,5).…”