• The Korean Journal of Physiology and Pharmacology
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• v.1 no.1
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• pp.107-115
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• 1997

We studied the effects of bile acids on the induction ofapoptosis in HepG2 human hepatocellular carcinoma cells. Treatment with either ursodeoxycholic acid (UDCA) or lithocholic acid (LCA) resulted in a dose- and time-dependent decrease in cell viability assessed by MTT assay. Both UDCA and LCA also induced genomic DNA fragmentation, a hallmark of apoptosis, indicating that the mechanism by which these bile acids induce cell death was through apoptosis. Cycloheximide, a protein synthesis inhibitor, blocked the apoptosis induced by these bile acids, implying that new protein synthesis may be required for the apoptosis. Intracellular $Ca^{2+}$ release blockers (dantrolene and 3,4,5-trimethoxybenzoic acid-8-(diethylamino)octyl ester) inhibited decreased cell viability and DNA fragmentation induced by these bile acids. Treatment of HepG2 cells with calcium ionophore A23l87 induced DNA fragmentation. These results suggest that UDCA and LCA induce apoptosis in the HepG2 cells and that the activation of intracellular $Ca^{2+}$ signals may play an important role in the apoptosis induced by these bile acids.

• Journal of Life Science
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• v.22 no.6
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• pp.815-822
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• 2012

Piceatannol (trans-3,4,3',5'-tetrahydroxystilbene), a natural stilbene, is an analogue of resveratrol. Although recent experimental data have revealed the health benefit potency of piceatannol, the molecular mechanisms underlying the anti-cancer activity have not yet been studied in detail. In the present study, the further possible mechanisms by which piceatannol exerts its pro-apoptotic action in cultured human lung cancer A549 cells were investigated. Exposure of A549 cells to piceatannol resulted in growth inhibition and induction of apoptosis. Apoptosis induction of A549 cells by piceatannol showed correlation with proteolytic activation of caspase-3, -8, and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase, phospholipase C-${\gamma}1$, ${\beta}$-catenin, and Inhibitor caspase-activated DNase. The increase in apoptosis by piceatannol treatment was also associated with an increase of pro-apoptotic Bax expression and decrease of anti-apoptotic Bcl-2 and Bcl-xL expression, and caused down-regulation of the inhibitor of apoptosis protein family members and up-regulation of Fas and Fas legend. In addition, piceatannol treatment markedly inhibited the expression of mRNA and proteins of inducible nitric oxide (NO) synthase, and the levels of NO production were progressively down-regulated by piceatannol treatment in a dose-dependent fashion. The results indicate that piceatannol may have therapeutic potential against human gastric cancer cells.

• The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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• v.24 no.1
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• pp.16-24
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• 2011

Objective : In this study, we investigated the effects of ethanol extract of Anemarrhenae Rhizoma (EAR) on the proliferation and apoptosis induction of HT-29 human colon cancer cells. Methods : Cell viability of HT-29 cells were measured by MTT assay and apoptisis-related proteins were assessed using western blotting. Chromatin condensation of HT-29 cells stained with Hoechst 33258. Results : In the present study, we demonstrated that EAR exhibited significant cytotoxicity in HT-29 cells. The induction of apoptosis in HT-29 cells by EAR treatment was characterized by chromatin condensation and the activation of caspase-3. EAR-induced apoptosis is accompanied by the release of cytochrome c and the specific proteolytic cleavage of PARP. EAR was appeared cytotoxic effect to HT-29 cells in a dose-dependent manner. Concomitantly, EAR treatment led to increase in the caspase-9. The reduction of Bcl-2 and truncation of Bid were induced by EAR. Conclusion : We studied that the EAR induced apoptosis in human colon adenocarcinoma HT-29 cells. These results indicated that EAR can cause apoptosis through mitochondria/caspase pathway in human HT-29 cells.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2020.08a
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• pp.77-77
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• 2020

Purple loosestrife-Lythrum anceps (Koehne) Makino is a herbaceous perennial plant belonging to the Lythraceae family. It has been used for centuries in Korea and other Asian traditional medicine. It has been showed pharmacological effects, including anti-oxidant and anti-microbial effects. However, the mechanisms underlying its anti-cancer mechanisms are not yet understood. In this study, we investigated the mechanism of apoptosis signaling pathways by ethanol extract of Lythrum anceps (Koehne) Makino (ELM) in human leukemia U937 cells. Treatment with ELM significantly inhibited cell growth in a dose-dependent manner by inducing apoptosis, as evidenced by the formation of apoptotic bodies (ApoBDs), DNA fragmentation and increased populations of sub-G1 ratio. Induction of apoptosis by ELM was connected with up-regulation of death receptor (DR) 4 and DR5, pro-apoptotic Bax protein expression and down-regulation of anti-apoptotic Bcl-2 protein, and inhibitor of apoptosis protein (IAP) family proteins (XIAP, cIAP-1, survivin), depending on dosage. This induction was associated with Bid truncation, mitochondrial dysfunction, proteolytic activation of caspases (-3, -8 and -9) and cleavage of poly(ADP-ribose) polymerase protein. Therefore, our data indicate that ELM suppresses U937 cell growth by activating the intrinsic and extrinsic apoptosis pathways, and thus may have applications as a potential source for an anti-leukemic chemotherapeutic agent.

• Herbal Formula Science
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• v.10 no.1
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• pp.143-155
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• 2002

In the hope of identifying anti-leukemic agents from traditional herbal medicines. this study was designed to investigate the anti-leukemic effects of the herbal medicine Jipaesan, which is composed of Angelica Dahurica and Fritillariae Verticillata. in acute promyeloid leukemia HL-60 cells. Jipaesan showed anti-proliferative effect through the induction of differentiation and apoptosis in HL -60 cells. Verticinone as a major differentiating agent and imperatorin as major apoptosis-inducing agent were isolated from the water extracts of F. Verticillata and A. Dahurica, respectively. Combined treatment of HL-60 cells with two major compounds showed synergy in the induction of differentiation. Since the induction of differentiation and/or apoptosis has therapeutic values in curing acute leukemic diseases. Jipaesan could be useful as an anti-leukemic agent.

• Korean journal of applied entomology
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• v.55 no.3
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• pp.267-275
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• 2016

Chlorine dioxide has an insecticidal activity via its production of reactive oxygen species (ROS). Its cytotoxic activity has been regarded as a main cause of the insecticidal activity. This study tested a hypothesis that cytotoxicity of chlorine dioxide is resulted from its induction of apoptosis against target cells using ROS. Injection of chlorine dioxide significantly reduced total hemocyte counts of Plodia interpunctella larvae and subsequently killed the larvae. To analyze the cytotoxicity with respect to apoptosis, terminal deoxyribonucleotidyl transferase nick end translation (TUNEL) assay was performed. An insect cell line (Sf9) cells were exposed to different concentrations of chlorine dioxide. TUNEL assay showed that chlorine dioxide induced significant apoptosis of Sf9 cells in a dose-dependent manner. When different concentrations of chlorine dioxide were injected to larvae of P. interpunctella, it showed a dose-dependent induction of apoptosis against hemocytes. However, addition of vitamin E significantly suppressed the apoptosis induction and insecticidal activity of chlorine dioxide in a dose-dependent manner. These results suggest that cytotoxicity of chlorine dioxide is resulted from its induction of apoptosis against insect cells using ROS.

• BMB Reports
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• v.47 no.8
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• pp.433-438
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• 2014

Plant sterols have shown potent anti-proliferative effects and apoptosis induction against breast and prostate cancers. However, the effect of sterols against hepatic cancer has not been investigated. In the present study, we assessed whether the stigmasterol isolated from Navicula incerta possesses apoptosis inductive effect in hepatocarcimona (HepG2) cells. According to the results, Stigmasterol has up-regulated the expression of pro-apoptotic gene expressions (Bax, p53) while down-regulating the anti-apoptotic genes (Bcl-2). Probably via mitochondrial apoptosis signaling pathway. With the induction of apoptosis caspase-8, 9 were activated. The DNA damage and increase in apoptotic cell numbers were observed through Hoechst staining, annexin V staining and cell cycle analysis. According to these results, we can suggest that the stigmasterol shows potent apoptosis inductive effects and has the potential to be tested as an anti-cancer therapeutic against liver cancer.

• Journal of Life Science
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• v.8 no.1
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• pp.51-59
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• 1998

The apoptosis-inducing activity of ursolic acid (UA) was examined in mouse F9 teratocarcinoma cells on the bases of biochemical and morphological characteeristics. UA, pentacyclic trierpene acid, exhibits antitumor activities including inhibition of skin tumorigenesis, induction of tumor cell differentiation and antitumor promotion. Treatment with UA showed that the decrease of cell viability was dose-dependent. UA also induced genomic DNA fragmetation, a hallmark of apoptosis, indicating that the mechanism of UA-induced F9 cell death was through apoptosis. When the morphology of the F9 cells was examined by electron microscopy, the cells treated with UA showed the charcteristic morphological features of apoptosis such as chromatin condensation and nuclear fragmentation. DNA fragmentations by UA were inhibired by cycloheximide, which suggest that de novo protein synthesis was required for DNA fragmentation by UA. Inaddition, the expression of c-jun was increased, but those of c-myc and laminin B1 were decreased during apoptosis induced by UA in F9 cells. These results suggest that UA causes an apoptosis in F9 cells. Further, the increased expression of c-jun may be involved in the UA-induced apoptosis of f9 cells.

• Journal of Food Hygiene and Safety
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• v.15 no.1
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• pp.41-45
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• 2000

Induction of DNA fragmentation of rat embryonic midbrain cells was studied to see whether apoptosis plays a role in OTA-induced microcephaly observed in cultured rat whole embryos during embryogenesis. We first cultured whole embryos (prepared from day 9.5 gestation rats) for 48 hrs with OTA and found that OTA induced microcephaly in cultured rat whole embryos. We also examined whether the microcephaly seen in cultured whole embryos is partially related to the increase of apoptosis of undifferentiated embryonic midbrain cells. Embryonic midbrain cells were prepared from day 12 gestation rat embryos, and cultured in the mixture media of Dulbecco's modified eagle's medium nutrient and Ham's F12 (1：1) containing 10% Nuserum, 100 $\mu\textrm{g}$/ml of streptomycin and 100 units/ml of penicillin for 96 hrs. Induction of DNA fragmentation was increased by 0.25-1 $\mu\textrm{g}$/ml OTA in a dose dependent manner in the embryonic midbrain cells. We also tested whether increase of apoptosis by OTA would be associated with change of apoptosis-related proteins (TNF-$\alpha$ and P$^{53}$ ) level in embryonic midbrain cells. OTA also increased TNF-$\alpha$ and P$^{53}$ levels. These results show that OTA induced microcephaly in cultured whole embryos and this effect may be at least a part due to the induction of apoptosis and apoptosis-related protein levels of undifferentiated embryonic midbrain cells.

• Journal of Life Science
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• v.27 no.11
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• pp.1340-1348
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• 2017

Sanguinarine is a benzophenanthridine alkaloid derived from the roots of Sanguinaria canadensis L., which is used for the purpose of treating various diseases. Although studies of anticancer activities have been performed using various cancer cell lines, the phenomenon of inducing apoptosis in cancer cells by using sanguinarine requires more research. Therefore, this study investigated the anti-cancer activities and related mechanisms of sanguinarine used with Hep3B human hepatocellular carcinoma cells in terms of the regulation of apoptosis. Sanguinarine inhibited the proliferation of Hep3B cells in a concentration-dependent manner, which was associated with the induction of apoptosis. Sanguinarine also increased the activity of caspase-3, which is a typical effector caspase, and the activities of caspase-8 and caspase-9, which are key when initiating extrinsic and intrinsic apoptosis pathways, respectively. In addition, sanguinarine increased the expression of death receptor-related genes and pro-apoptotic BAX, which belongs to the Bcl-2 family, while suppressing the expression of anti-apoptotic Bcl-2. Sanguinarine promoted the truncation of Bid and enhanced the release of cytochrome c from the mitochondria to the cytoplasm due to a loss of mitochondrial membrane potential. Furthermore, the reduction of a survival rate that was induced by sanguinarine and the induction of apoptosis disappeared with the inhibition of artificial caspase activity. Therefore, the results of the study indicated that sanguinarine-induced apoptosis in Hep3B cells involves both extrinsic and intrinsic pathways; such apoptosis is a caspase-dependent phenomenon.