Immunomodulatory effects of curcumin: in-vivo.

Curcumin specifically exhibits cytostatic and cytotoxic effects against tumors of multiple origin. Previously we have demonstrated apoptotic activity of curcumin against tumor cells with no effect on normal cells in-vitro. Many anti-cancer drugs exhibit deleterious effects on immune cells, which restrict their wide use in-vivo.

Heat stress induced apoptosis in BC-8 cells derived from AK-5 tumor involves downregulation of Bcl-2 and generation of reactive oxygen species.

BC-8, a rat histiocytoma undergoes apoptosis after heat shock, which is due to lack of an effective heat shock response. Heat shock induced generation of free radicals, which in turn are involved in the induction of apoptotic death in BC-8 cells. Treatment of BC-8 cells with N-acetylcysteine partially inhibited the heat induced apoptosis.

Role of STAT3 and NFkappaB signaling in the serum factor-induced apoptosis in AK-5 cells.

AK-5, a rat histiocytoma, is rejected in about 70% of the syngeneic animals when injected subcutaneously. The sera from the tumor rejecting animals possess a potent factor, referred to as serum factor (SF) that induces apoptosis in AK-5 tumor cells. In the present study, we show that treatment with SF or JAK/STAT inhibitors AG490 and Piceatannol induces apoptosis to a similar extent in BC-8 (a single cell clone of AK-5) cells.

Differential cytotoxic effects of Annona squamosa seed extracts on human tumour cell lines: role of reactive oxygen species and glutathione.

Annonaceous acetogenins are a new class of compounds that have been reported to have potent pesticidal, parasiticidal, anti-microbial, cell growth inhibitory activities. In this study, organic and aqueous extracts from the defatted seeds of Annona squamosa (custard apple) were tested on different human tumour cell lines for antitumoural activity. While organic and aqueous extracts induced apoptosis in MCF-7 and K-562 cells, they failed to do so in COLO-205 cells.

Differential apoptotic and redox regulatory activities of curcumin and its derivatives.

We have synthesized different bioconjugates of curcumin, which were tested for their pro- and antioxidant properties. In the present study five representative derivatives of curcumin, i.e.

Antitumour activity of Annona squamosa seed extracts is through the generation of free radicals and induction of apoptosis.

The plant, Annona squamosa traditionally known as custard apple possesses potent bioactive principles in all its parts. The effect of aqueous and organic extracts from defatted seeds of A. squamosa was studied on a rat histiocytic tumour cell line, AK-5.

Phycocyanin-mediated apoptosis in AK-5 tumor cells involves down-regulation of Bcl-2 and generation of ROS.

C-phycocyanin, which is a major biliprotein of the blue-green algae, has been shown to possess cyclooxygenase-2 inhibitory activity. We have studied the effect of phycocyanin on a rat histiocytic tumor line. AK-5 cells are induced into apoptotic death program when treated with phycocyanin, which involves the activation of caspase-3.

Protection conferred by Bcl-2 expression involves reduced oxidative stress and increased glutathione production during hypothermia-induced apoptosis in AK-5 tumor cells.

Hypothermia is known to retard mammalian cell growth, however, BC-8 cells, which have originated from AK-5 tumor after single cell cloning, were triggered into apoptotic pathway when grown at 30 degrees C. Cell death process showed typical apoptotic features like DNA fragmentation, cytochrome c release, etc. Introduction of Bcl-2 gene in BC-8 cells inhibited hypothermia-induced apoptotic process, which is ascribed to reduced ROS generation and higher glutathione production.

Effect of C-terminal deletion of P53 on heat induced CD95 expression and apoptosis in a rat histiocytoma.

Tumor suppressor gene product p53 in its wild-type conformation, is an effector of apoptosis. A rat histiocytic tumor, AK-5 which has a rearranged and mutated p53 gene undergoes apoptosis upon heat shock through surface expression of CD95 receptor. DNA sequence analysis of p53 gene from tumor cells revealed a deletion of 'C' at nucleotide position 942 and an addition of 'A' at position 1055.

A cross talk between cellular signalling and cellular redox state during heat-induced apoptosis in a rat histiocytoma.

Increasing evidence provides support for oxidative stress to be closely linked to apoptosis. Reactive oxygen species (ROS) are thought to be involved in many forms of programmed cell death. Though heat shock is a universal phenomenon, BC-8, a macrophage-like cell line failed to mount a typical heat shock response.

Induction of stress response renders human tumor cell lines resistant to curcumin-mediated apoptosis: role of reactive oxygen intermediates.

Curcumin, a well-known dietary pigment derived from Curcuma longa, has been shown to be a potent antiinflammatory, antioxidant, and anticarcinogenic compound. The present study was designed to investigate the cytotoxic potential of curcumin against a range of human tumor cell lines in an attempt to understand its mechanism of action, which may lead to its possible therapeutic applications. We have shown that different cancer cell lines differ in their sensitivity to curcumin.

Heat induced expression of CD95 and its correlation with the activation of apoptosis upon heat shock in rat histiocytic tumor cells.

The heat shock response is a universal phenomenon and is among the most highly conserved cellular responses. However, BC-8, a rat histiocytoma, fails to mount a heat shock response unlike all other eukaryotic cells. In the absence of induction of heat shock proteins, apoptotic cell death is activated in BC-8 tumor cells upon heat shock.

Induction of apoptosis in AK-5 cells by rotenone involves participation of caspases.

AK-5 tumour cells undergo apoptosis after treatment with rotenone an electron transport inhibitor and oligomycin which inhibits mitochondrial ATPases. Apoptotic process involves the induction of caspases 2 and 3, whereas caspase 1 does not seem to be participating in rotenone/oligomycin induced apoptosis. DEVD which is a specific inhibitor of caspase 3, inhibited apoptosis in AK-5 cells.

Lack of heat shock response triggers programmed cell death in a rat histiocytic cell line.

Stress response is a universal phenomenon. However, a rat histiocytic cell line, BC-8, showed no heat shock response and failed to synthesize heat shock protein 70 (hsp70) upon heat shock at 42 degrees C for 30 min. BC-8 is a clone of AK-5, a rat macrophage tumor line that is adapted to grow in culture and has the same chromosome number and tumorigenic potential as AK-5.

Curcumin mediated apoptosis in AK-5 tumor cells involves the production of reactive oxygen intermediates.

Curcumin, the active ingredient of the rhizome of Curcuma longa has anti-inflammatory, antioxidant and antiproliferative activities. Although its precise mode of action remains elusive, studies have shown that chemopreventive action of curcumin might be due to its ability to induce apoptosis in cancer cells. Curcumin was shown to be responsible for the inhibition of AK-5 tumor (a rat histiocytoma) growth by inducing apoptosis in AK-5 tumor cells via caspase activation.

Role of IFN-gamma produced after intraperitoneal transplantation of AK-5 cells in the induction of Fas ligand expression by tumor cells leading to immune evasion.

AK-5 tumor cells expressed Fas-L on their surface after intraperitoneal transplantation in syngeneic animals. Fas-L expression by AK-5 cells is involved in the killing of the effector cells. Thus, the tumor has developed an escape mechanism from immune attack.

Upregulation of antitumor immunity by IL-12 gene-transfected AK-5 tumor cells in vivo.

We have earlier demonstrated a significant role for IL-12 in the regression of a rat histiocytic tumor, AK-5. In order to analyze further the antitumor immunity induced by interleukin (IL)-12, we have established IL-12-secreting tumor cell clones by gene transfection. Significant enhancement in the lytic potential of splenocytes by the culture supernatants containing IL-12 demonstrated retention of biological activity by the tumor-cell-derived cytokine.

Antitumor activity of curcumin is mediated through the induction of apoptosis in AK-5 tumor cells.

Curcumin, the yellow pigment of turmeric (Curcuma longa), used commonly as a spice, has been shown to possess anticarcinogenic activity. Curcumin inhibited AK-5 tumor growth and induced apoptosis in AK-5 cells. Curcumin induced apoptosis is mediated through the activation of caspase-3, which is specifically inhibited by the tetrapeptide Ac-DEVD-CHO.

Depletion of the natural killer cell population in the peritoneum by AK-5 tumor cells overexpressing fas-ligand: a mechanism of immune evasion.

AK-5 tumor kills 100% hosts when injected ip and only 20-30% of animals die when the tumor cells are transplanted sc. Seventy percent of animals regress the subcutaneous tumor and exhibit total immunity against subsequent challenges of AK-5 cells by either route. Initially the 100% killing in ip-injected animals was attributed to the rapid growth of the tumor cells in the peritoneum thereby not giving enough time for the host immune system to mount an antitumor response.

Participation of CED-3/ICE and YAMA proteinases in the execution of apoptosis in AK-5 tumor cells leading to spontaneous tumor regression.

AK-5, which is a spontaneously regressing rat histiocytoma, is killed by necrosis (perforin mediated) and apoptosis. We have studied the induction of apoptosis in AK-5 tumor cells by each of the following: a factor from anti-AK-5 antiserum, dexamethasone, and natural killer cells. Partial inhibition in apoptosis was observed when AK-5 cells were transfected with Crm A gene, a specific inhibitor of ICE protease.

Effect of anti-apoptotic genes and peptide inhibitors on cytoplasmic acidification during apoptosis.

Cytoplasmic acidification has been shown to occur during the apoptotic process of cell death although its relation with other events in the process are not yet clear. AK-5 tumor cells have been shown to undergo apoptosis upon treatment with stimuli like dexamethasone (1 microM) or with serum from animals that reject AK-5 tumor. The current study was designed to measure the extent of cytoplasmic acidification during apoptosis in AK-5 cells and to study the effect of antiapopoptic genes and peptide inhibitors on cytoplasmic acidification.

Natural killer cell as the effector which mediates in vivo apoptosis in AK-5 tumor cells.

AK-5 tumor cell death is mediated by natural killer cells through necrosis (perforin mediated) and apoptosis. Apoptosis is the mechanism which operates in immune animals in vivo. We have identified natural killer (NK) cell as the effector cell which induces apoptosis leading to tumor cell death in vivo.

Increased apoptosis in AK-5 tumor cells after transfection with wild type p53 gene.

AK-5 tumor cell death is mediated through necrosis and apoptosis. The apoptotic activity in AK-5 cells has been studied after introduction of wild-type p53 gene. Apoptotic activity both in vitro and in vivo is significantly increased in p53 transfected cells.

Apoptosis: the in vivo mechanism which mediates spontaneous AK-5 tumor regression.

We have studied the mechanism of induction of apoptosis in a rat histiocytoma in vivo. Tumor cells are killed by necrosis and apoptosis when injected into immune animals; however, naive animals are incapable of killing the tumor cells. Tumor cells show DNA fragmentation within 3 h after transplantation in the peritoneal cavity.

Conjugate formation between effector and target as a function of cytotoxicity in antibody-dependent killing of AK-5 tumor.

The present study was carried out to mechanistically view a possible correlation between the process of, conjugate formation and its relation to target cell death. AK-5 killing is mediated by CD8+ natural killer cells through ADCC. Immune effectors on exposure to antibody primed AK-5 tumor cells formed tight conjugates.