• Korean Journal of Medicinal Crop Science
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• v.12 no.4
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• pp.315-320
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• 2004

The purpose of this research was to investigate the effect of Orostachys japonicus A. Berger (OJB) on the immune system. Administration of OJB (500 mg/kg) enhanced viability of splenocytes and thymocytes in BALB/c mice, and also OJB increased of splenic T lymphocytes, significantly, increased CD4 positive $T_H$ cells and CD8 positive Tc cells. OJB markedly, enhanced the production of ${\gamma}-interferon$ in mice serum. OJB accelerated the apoptosis of L1210 and U937 leukemia cells and increased the expression of apoptosis-related ICE, c-myc, p53 gene. These results suggest that OJB have an immuno-regulatory and anti-cancer activity.

• BMB Reports
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• v.49 no.1
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• pp.63-68
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• 2016

The serine/threonine kinase mTOR is essential for the phosphoinositide 3-kinases (PI3K) signaling pathway, and regulates the development and function of immune cells. Aberrant activation of mTOR signaling pathway is associated with many cancers including leukemia. Here, we report the contributions of mTOR signaling to growth of human leukemic cell lines and mouse T-cell acute leukemia (T-ALL) cells. Torin, an ATP-competitive mTOR inhibitor, was found to have both cytotoxic and cytostatic effects on U-937, THP-1, and RPMI-8226 cells, but not on Jurkat or K-562 cells. All cells were relatively resistant to rapamycin even with suppressed activity of mTOR complex 1. Growth of T-ALL cells induced by Notch1 was profoundly affected by torin partially due to increased expression of Bcl2l11 and Bbc3. Of note, activation of Akt or knockdown of FoxO1 mitigated the effect of mTOR inhibition on T-ALL cells. Our data provide insight on the effect of mTOR inhibitors on the survival and proliferation of leukemic cells, thus further improving our understanding on cell-context-dependent impacts of mTOR signaling. [BMB Reports 2016; 49(1): 63-68]

• Proceedings of the Korean Society of Life Science Conference
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• 2005.04a
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• pp.104-104
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• 2005

• Proceedings of the Korean Society of Life Science Conference
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• 2005.04a
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• pp.102-103
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• 2005

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.2
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• pp.607-611
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• 2012

Non-toxic stimulation of dendritic cells (DCs), which are central immunomodulators, may aid the prevention of cancer. Furthermore, induction of apoptosis in cancer cells by anticancer agents contributes to the induction of DC maturation. We previously reported that extracts from $Pinus$ $parviflora$ Sieb. et Zucc pine cone and $Mucuna$ seed induce differentiation of mouse bone marrow cells into mature dendritic cells and also induce apoptosis in various human cancer cell lines. In the present study, we screened 31 kinds of edible beans with biological activity similar to that of extracts from pine cone and $Mucuna$ and found that the heat-stable extract from azuki bean ($Vigna$ $angula$) stimulated differentiation of bone marrow cells into immature DCs with the greatest efficacy. The level of IL-6 produced by sequential treatment of DCs with azuki extract and lipopolysaccharide was the highest among the examined beans. Azuki extract also inhibited the growth of human leukemia U937 cells, leading to induction of apoptosis. These results suggest that azuki bean and its extract are immunopotentiating foods that can be used as a dietary supplement for cancer prevention and immunotherapy.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.6
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• pp.1143-1150
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• 2002

Recent evidence suggests that many Oriental Medicinal prescriptions are effective in cancer patients as a supportive care. Oriental Medicinal herbs have been investigated extensively and are known to have multiple pharmacological effect. These herbs contain a variety of ingredients which may act synergistically to inhibit tumor cell division, to increase tumor cell death (apoptosis), and to increase the proportion of immune cells within tumor. Paljinhangahm-dan (Paljin) has been used to treat for cancer patients in Oriental Medicine for decades. The effects of aqueous extract of Paljin on the induction of apoptotic cell death were investigated in human leukemia cell lines (HL-60, Jurkat, Molt-4 and U937). The viability of leukemia cells was markedly decreased by Paljin in a dose-dependent manner. Paljin induced the apoptotic death of leukemia cells, which was characterized by the ladder-pattern DNA fragmentation, and chromatin condensation of the nuclei. Paljin digested Bid protein but did not affect Bcl-2 protein level and also, induced mitochondrial dysfunction disrupted as shown as the mitochondrial membrane potential. It activated caspase-9 and caspase-3. thereby resulted in cleavage of poly(ADP) ribose polymerase(PARP). These results indicate that Paljin induces apoptosis of human leukemia cells via activation of intrinsic caspase cascades with mitochondrial dysfunction.

• Journal of the Korean Chemical Society
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• v.41 no.7
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• pp.357-361
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• 1997

8-Azaxanthine (1), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine (2), 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-monophosphate (3), and 3-${\beta}$-D-ribofuranosyl-8-azaxanthine-5'-(3-pyridinylcarbonyl)monophosphate (4) were synthesized. The in vitro antitumor activities of the synthesized compounds against P388 mouse leukemia, FM3A mammary carcinoma, and U937 human histiocytic lymphoma cells were determined by MTT assay. 2 with unnatural N-3 and C-1' glycoside bond had activity against three tumor cell lines and $IC_{50}$s of these compounds were 0.05, 0.06, and 0.06 ${\mu}mol/mL$ against three tumor cell lines, respectively. But these compounds had no antibacterial activity. $IC_{50}$s against U937 human histiocytic lymphoma cells were verified with the structural modification: $IC_{50}$s of 1, 2, 3, and 4 were 0.33, 0.06, 0.25, and 0.33 ${\mu}mol/mL$, respectively.

• Journal of Microbiology and Biotechnology
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• v.15 no.3
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• pp.532-536
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• 2005

In the course of our screening for small molecules to inhibit apoptosis of U937 human leukemia cells induced by etoposide ($10\;{\mu}g/ml$), Penicillium sp. F020150 with potent inhibitory activity was selected. The active compound was purified from ethyl acetate extract of the microorganism by Sephadex LH-20 column chromatography and HPLC, and was identified as gentisyl alcohol (2,5-dihydroxybenzyl alcohol) by spectroscopic methods. The compound inhibited caspase-3 induction with $IC_{50}$ value of $3.0\;{\mu}g/ml$ after 8 h of etoposide treatment. The expression levels of caspase-3 and PARP were dose-dependently inhibited by the compound, suggesting that gentisyl alcohol inhibits etoposide-induced apoptosis via downregulation of caspases.

• Bulletin of the Korean Chemical Society
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• v.18 no.7
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• pp.711-714
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• 1997

In an effort to enhance the lipophilicities, thereby, the penetration into the cell membrane and to increase the antitumor activities of modified derivatives of 2',3'-didehydro-3'-deoxythymidine (d4T, 1), derivatives of 1 were designed and synthesized. Starting from thymidine, 1, 2',3'-didehydro-3'-deoxythymidine-5'-phosphate, disodium salt (d4T-p, 7), and two nicotinate esters of 1; 2',3'-didehydro-3'-deoxy-5'-O-(3-pyridinylcarbonyl)thymidine (d4T-NA, 5) and 2',3'-didehydro-3'-deoxy-5'-phosphoryl-O-(3-pyridinylcarbonyl)thymidine (d4T-p-NA, 8) were synthesized. The lipophilicities of the synthesized compounds were measured by P-values and antitumor activities of those were estimated against mouse leukemia P388, murine mammary carcinoma FM3A, and human histiocytic lymphoma U937 tumor cells in vitro. Although the lipophilicities of the nicotinate esters, 5 and 8 were increased 2.75- and 9.71-fold relative to that of 1 and 7, respectively, the synthesized compounds, 1, 5, 7, and 8 were found to be inactive against P388 and FM3A cells except weak antitumor activity against U937 cell.

• Journal of Life Science
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• v.23 no.3
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• pp.389-398
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• 2013

Platycodin D is a major constituent of triterpene saponins, which is found in the root of Platycodon grandiflorum, Platycodi Radix, which is widely used in traditional Oriental medicine for the treatment of many chronic inflammatory diseases. Several pharmacological effects of this compound have been reported recently, such as anti-inflammation, immunogenicity, anti-adipogenesis, lowered cholesterol, and anti-cancer activity. However, the mechanism by which this action occurs is poorly understood. In this study, we found that platycodin D greatly increased the potential of the anti-proliferative effect in various cancer cell lines. Our data revealed that platycodin D treatment resulted in a time- and concentration-response growth inhibition of U937 cells by inducing apoptosis, as evidenced by the formation of apoptotic bodies, chromatin condensation, and the accumulation of cells in the sub-G1 phase. Apoptosis induction of U937 cells by platycodin D correlated with an increase in the Bax/Bcl-2 ratio and caused the down-regulation of IAP family members. In addition, platycodin D treatment resulted in proteolytic activation of caspase-3, the concomitant degradation of poly(ADP-ribose) polymerases, and the collapse of the mitochondria membrane potential (${\Delta}{\Psi}_m$). However, the cytotoxic effects induced by platycodin D treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrated the important role that caspase-3 played in the observed cytotoxic effect. These findings suggest that platycodin D may be a potential chemotherapeutic agent for use in the control of human leukemia U937 cells. These findings also provided important new insights into possible molecular mechanisms of the anti-cancer activity of platycodin D.