Diterpenylhydroquinones from Natural ent-Labdanes Induce Apoptosis through Decreased Mitochondrial Membrane Potential

Abstract

In this study, we examined the cytotoxic effects of seven ent-labdane derivatives 1–7 (0–100 μM) in different human cancer cell lines. Our results showed that compounds 1–3 exhibited significant dose-dependent inhibition on the growth of the three different human cell lines, according to the sulphorhodamine B assay and produced morphological changes consistent with apoptosis, as confirmed by Hoestch 3342 staining analysis. They induced apoptosis in various cancer cell lines, as shown by nuclear condensation and fragmentation and caspase 3 activation. Such induction was associated with the depletion of mitochondrial membrane potential. These activities led to the cleavage of caspases and the trigger of cell death process. Overall, the compounds showed potent proapoptotic effects on the two different cancer cell lines, suggesting that the compounds deserve more extensive investigation of their potential medicinal applications.

Study on the Cytotoxic Activity of Drimane Sesquiterpenes and Nordrimane Compounds against Cancer Cell Lines

“…Mitochondria play a crucial role in the apoptotic cascade by serving as a convergent center of apoptotic signals originating from both the extrinsic and intrinsic pathways [19]. Changes induced in the mitochondrial membrane potential (MMP) have been reported previously to represent a determinant in the execution of cell death [20]. As polygodial has been described as an inhibitor of mitochondrial ATPase and also as nonionic surfactant [21,22,23].…”

Synthesis and Antiproliferative Activity of New Cyclodiprenyl Phenols against Select Cancer Cell Lines

“…Mitochondria play an important role in the cell death fate by serving as a convergent center of apoptotic signals originated from both the extrinsic and intrinsic pathways [ 39 ]. The changes induced in the mitochondria membrane potential have been previously reported to represent a determinant in the execution of cell death [ 40 ]. We analyzed the possible changes induced by the studied compounds in the mitochondrial membrane potential, using rhodamine 123 to track down changes in mitochondrial function, since fluorescence of the dye decreases as mitochondrial membrane potential is lost [ 41 ].…”

“…Morphological changes in the nuclear chromatin of cells undergoing apoptosis were revealed by a nuclear fluorescent dye, Hoescht 33342 (Sigma-Aldrich, Santiago, Chile) [ 40 ]. Briefly, on 24-well chamber slides, 1 × 10 4 cells/mL MCF-7, PC-3 and HDF were cultured and exposed to 25 μM compounds for 48 h. The control group was also exposed to ethanol 1%.…”

“…Rhodamine 123, a cationic voltage-sensitive probe that accumulates in mitochondria was used to track down changes in mitochondrial membrane permeability [ 40 ]. Exponentially growing cells were incubated with compounds as indicated previously.…”

Apoptosis is induced by shikonin through the mitochondrial signaling pathway

“…The death of tumor cells is predominantly induced via three mechanisms: Necrosis, apoptosis and autophagy. Previous studies reported that SHI induced tumor cell death through the apoptotic signaling pathway, and may act by inhibiting the activation of nuclear factor (NF)-κB (14); upregulating caspase proteases (15); inhibiting the expression of survivin (16); regulating the mRNA and protein expression of B cell lymphoma 2 (Bcl-2) family-associated genes (8), p53 (8), c-myc (7) and Fas (9); and altering the mitochondrial membrane potential (17). Previous studies have also reported that SHI induced cell death through the non-apoptotic pathway (autophagy and necrosis-like programmed cell death) (14,15).…”