The chemopreventive agent N-(4-hydroxyphenyl)retinamide induces apoptosis through a mitochondrial pathway regulated by proteins from the Bcl-2 family

Interplay between bax, reactive oxygen species production, and cardiolipin oxidation during apoptosis

“…A significant increase of superoxide generation occurred after 8 h incubation in WT MEF cells. In line with previous studies [14,15], no increased superoxide generation was observed in Bax/Bak DKO MEF cells under the same conditions (Fig. 1C).…”

N-(4-Hydroxyphenyl)retinamide-induced apoptosis triggered by reactive oxygen species is mediated by activation of MAPKs in head and neck squamous carcinoma cells

“…JNK inhibitor suppresses cytochrome c release from mitochondria JNK has been shown to be required for cytochrome c release from mitochondria in stress-induced apoptosis (Tournier et al, 2000) and 4HPR has been shown to induce cytochrome c release from mitochondria in various cell types (Suzuki et al, 1999;Asumendi et al, 2002;Boya et al, 2003). To delineate the mechanism of JNK function in 4HPR-induced apoptosis in 22B cells, we examined the effect of SP600125 on mitochondrial events induced by 4HPR.…”

“…cytochrome c, apoptosisinducing factor) are released from mitochondria (Robertson and Orrenius, 2002;Zamzami and Kroemer, 2003). Increase in mitochondrial membrane permeability has been shown to be a central event in 4HPR-induced cell death in some cells (Hail and Lotan, 2000;Poot et al, 2002;Boya et al, 2003). To determine whether 4HPR can induce changes in membrane permeability in HNSCC22B cells, the inner membrane potential was monitored after 4HPR treatment by using the mitochondria-specific dye CMXRos.…”

“…4HPR appears to induce apoptosis predominantly by the activation of the mitochondrial pathway (Suzuki et al, 1999;Hail and Lotan, 2000;Boya et al, 2003). Increased generation of reactive oxygen species (ROS) (Delia et al, 1997;Suzuki et al, 1999;Hail and Lotan, 2001), increased ceramide production (Maurer et al, 1999), induction of mitochondrial permeability transition (MPT) (Suzuki et al, 1999;Hail and Lotan, 2000;Poot et al, 2002;Boya et al, 2003), cytochrome c release (Suzuki et al, 1999;Asumendi et al, 2002;Boya et al, 2003), increased GADD153 (Kim et al, 2002;Lovat et al, 2002), and activation of 12-lipoxygenase (Lovat et al, 2002) or activation of c-Jun N-terminal kinase (JNK) (Chen et al, 1999;Shimada et al, 2002;Osone et al, 2004) have been implicated in 4HPR-mediated apoptosis in various cancer cells.…”

N-(4-hydroxyphenyl)retinamide promotes apoptosis of resting and proliferating B-cell chronic lymphocytic leukemia cells and potentiates fludarabine and ABT-737 cytotoxicity

“…11,12 N-(4-hydroxyphenyl)retinamide (4HPR, fenretinide) is a synthetic retinoid with chemopreventive/cytotoxic activity against various cancers. [13][14][15][16][17] 4HPR was shown to induce apoptosis in solid and hematologic tumor cells through reactive oxygen species (ROS) generation [18][19][20][21] and Bcl-2/Mcl-1 decrease. 18,22 No studies have examined the activity of 4HPR on CLL cells.…”