Furano-sesquiterpene from soft coral, Sinularia kavarittiensis: induces apoptosis via the mitochondrial-mediated caspase-dependent pathway in THP-1, leukemia cell line

Abstract

Bioassay directed fractionation and purification led to the successful isolation of a furano sesquiterpene, Methyl 5-[(1E,5E)-2,6-Dimethyl octa-1,5,7-trienyl] furan-3-carboxylate (MDTFC), a bioactive component from a soft coral, Sinularia kavarittiensis. Its structure was determined by analyzing (1)H, (13)C NMR and FAB-MS. The results show that MDTFC could efficiently and selectively inhibit the proliferation of several human cancer cell lines. Among all the cell lines, THP-1 was found to be most sensitive (IC(50) 29.59 microM), whereas the peripheral blood mononuclear cells were least effected (IC(50) 464.16 microM). The molecular mechanism of MDTFC mediated apoptosis was investigated for the first time. Induction of apoptosis in THP-1 cells was characterized by cell membrane blebbing, chromatin condensation, DNA fragmentation, and decrease in level of pro-caspases 3, 9 and increase in Bax/Bcl-2 ratio. Our results were further strengthened through cleavage of poly (ADP-ribose) polymerase, reduction of mitochondrial membrane potential (Psim) and cytosolic release of cytochrome c, which are key events during apoptosis. Moreover, phosphatidyl serine exposure and appearance of sub-G1 peak also demonstrated cell death, when analyzed by flow cytometry. DNA fragmentation was prevented moderately when pretreated with caspase-9 inhibitor (Z-LEHD-FMK) and largely with caspase-3 inhibitor (Z-DEVD-FMK). In summary, MDTFC mediated apoptosis involves mitochondria-dependent pathway and the present compound of marine origin might have a therapeutic value against human cancer cell lines and especially on leukemia cells.

Synthesis and Evaluation of the Cytotoxic Activities of Some Isatin Derivatives

“…4). The results, which are consistent with those coming from previous studies, 35) suggest that 4d induces apoptosis by internucleosomal DNA cleavage, a biochemical event used as a definitive apoptotic marker that signifies the possibility that 4d is a potential drug lead for cancer chemotherapy.…”

“…35) Initially, HeLa cells were harvested, washed with phosphate-buffered saline (PBS), and then lysed with digestion buffer containing 50 mM Tris-HCl, 0.5% sodium dodecyl sulfate (SDS), 1 µg/mL proteinase k (pH 8.0), and 10 mM EDTA at 37°C overnight. The cells were then treated with RNase A (0.5 µg/mL) for 1 h at 37°C.…”

Spatane diterpinoid from the brown algae, Stoechospermum marginatum induces apoptosis via ROS induced mitochondrial mediated caspase dependent pathway in murine B16F10 melanoma cells

“…Cancer growth is associated with the loss of cell cycle checkpoints that regulate the passage through cell cycle. These check points monitor the integrity of DNA and ensure that the genes are expressed in a co-ordinate manner [24]. Cell cycle analysis showed an "S-phase" population on DDSD treated B16F10 cells, which indicated that the cell death was caused by apoptosis (Figure 4b and c).…”

“…Cell cycle analysis and mitochondrial membrane potential were performed as earlier described protocol [24] at the optimal setting of the instrument and proper filters, the samples were recorded as a FCS file and analyzed by FCS express-4 software after the exclusion of the debris and clumps.…”

Sinulariolide Suppresses Cell Migration and Invasion by Inhibiting Matrix Metalloproteinase-2/-9 and Urokinase through the PI3K/AKT/mTOR Signaling Pathway in Human Bladder Cancer Cells

“…In the current therapeutic approach, inhibition of the mechanism associated with tumor cell migration/invasion is the key to controlling cancer metastasis [17]. Many of the active ingredients isolated from corals have been shown to possess properties that prevent cancer cell proliferation and metastasis [12,[18][19][20][21][22][23]. …”