• Journal of Life Science
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• v.34 no.7
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• pp.476-484
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• 2024

Although two-dimensional (2D) monolayer cell culture models are still widely used as the optimal models for anticancer activity research, three-dimensional (3D) multicellular tumor spheroid (3D MTS) models that can better approximate the tumor environment can offer an alternative to bridge the gap between in vitro and animal model studies. Isoalantolactone is among the sesquiterpene lactones found in medicinal plants, including the roots of Elecampane (Inula helenium L.), and is known to have various pharmacological activities, including anticancer activity. In this study, we investigated whether the anticancer activity of isoalantolactone observed in 2D models could be reproduced in a 3D MTS model derived from human hepatocellular carcinoma (HCC) Hep3B cells. According to our results, isoalantolactone inhibited the formation of MTSs in a manner dependent on the treatment concentration, which was accompanied by an increase in reactive oxygen species (ROS) generation. In particular, as isoalantolactone treatment and the culture time increased, the area of proliferating cells was replaced by cells in which apoptosis was induced. Additionally, in MTSs, isoalantolactone increased the expression of death-receptor-related proteins and the activity of caspase-3, and it decreased the expression of the Bax/Bcl-2 expression ratio and total poly(ADP-ribose) polymerase. However, when the production of ROS was artificially blocked, all these changes caused by isoalantolactone were attenuated and the cell survival rate of MTS cells was restored. Therefore, the results of this study suggest that the induction of apoptosis in Hep3B cell-derived MTSs by isoalantolactone is achieved through the activation of extrinsic and intrinsic pathways and is ROS-dependent.

• Korean Journal of Plant Resources
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• v.33 no.4
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• pp.279-286
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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 effect 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, 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.

• Journal of Life Science
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• v.25 no.12
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• pp.1384-1392
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• 2015

Sagantang (SGT), a Korean multiherb formula comprising six medicinal herbs, Paeonia lactiflora Pall., Belamcanda chinensis (L.) DC, Gardenia jasminoides Ellis, Poria cocos Wolf, Cimicifuga heracleifolia Komarov, and Artractylodes japonica Koidzumi, was recorded in “Dongeuibogam.” The present study investigated the anticancer potential of SGT in AGS human gastric carcinoma cells. The results indicated that SGT treatment significantly inhibited the growth and viability of AGS cells in a dose-dependent manner, which was associated with the induction of apoptotic cell death, as evidenced by the formation of apoptotic bodies, in addition to chromatin condensation and DNA fragmentation, and the accumulation of annexin-V positive cells. The induction of apoptotic cell death by the SGT treatment was associated with up-regulation of Fas protein expression, truncation of Bid, and down-regulation of the anti-apoptotic Bcl-2 protein. The SGT treatment also effectively induced the loss of mitochondrial membrane potential, which was associated with the activation of caspases (caspase-3, -8, and -9) and degradation of poly (ADP-ribose) polymerase. However, a pan-caspase inhibitor significantly blocked the SGT-induced apoptosis and growth suppression in AGS cells. This study suggests that SGT induces caspase-dependent apoptosis through an extrinsic pathway by upregulating Fas, as well as through an intrinsic pathway by modulating Bcl-2 family members in AGS cells. The results suggest that SGT may be a potential chemotherapeutic agent for the control of human gastric cancer cells. However, further studies will be needed to confirm the potential of SGT in cancer prevention and therapy in an in vivo model and to identify biological active compounds of SGT.

• Journal of Life Science
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• v.26 no.8
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• pp.887-894
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• 2016

The extract from Artemisia annuain L.(AAE) is known as a medicinal herb that is effective against cancer. Apoptosis is the process of programmed cell death, and mitochondria are known to play a central role in cell death control. In this study, we evaluated the p53-independent apoptosis of extract of AAE through downregulation of Bcl-2 and the mitochondrial pathway in A549 (lung cancer cells). AAE may exert cancer cell apoptosis through regulating p-Akt, Cox-2, p53 and mitochondria-mediated apoptotic proteins. p-Akt/cox-2 is known to play an important role in cell proliferation and cell survival. The Bcl-2 pro-apoptotic proteins (such as Bax, Bak and Bim) mediate the permeabilization of the mitochondrial outer membrane. Treatment of AAE reduces p-Akt, p-Mdm2, cox-2 and anti-apoptotic proteins (such as Bcl-2), while tumor suppressor p53 and pro-apoptotic proteins. Activation of Bax/Bak releases cytochrome c from mitochondria to the cytosol to activate a caspase. Caspase-3 is the major effector caspase associated with apoptotic pathways. Caspase-3 generally exists in cytoplasm in the form of a pro-enzyme. In the initiation stage of apoptosis, caspase-3 is activated by proteolytic cleavage and activated caspase-3 cleaves poly (ADP-ribose) polymerase (PARP). We treated Pifithrin-α (p53 inhibitor) and Celecoxib (Cox-2 inhibitor) to learn the relationship between the signal transduction of proteins associated with apoptosis. These results suggest that AAE induces apoptosis through a p53-independent pathway in A549.

• Korean Journal of Poultry Science
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• v.48 no.4
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• pp.207-216
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• 2021

This study was conducted to determine the nutritional quality of two newly-developed native chicken strains, compared to the commercial Korean native chicken. A total of 600 chickens (CON: Hanhyup No. 3, CL1: candidate line C, CL2: candidate line D) raised under the same conditions were slaughtered at either 5 or 12 weeks. Leg meat was then obtained and analyzed for its physicochemical properties. The results showed that regardless of the growing period, there was no variation in proximate composition (P>0.05), except for crude protein, between strains. Water holding capacity did not differ between strains at either slaughter age; however, it was significantly lower in the 12-week group than in the 5-week group (P≤0.05). For both skin and muscle color, a^* and b^* values were lower at 12 weeks than at 5 weeks (P≤0.05). DPPH radical-scavenging activity tended to be lower at 12 weeks than at 5 weeks (P≤0.05). Furthermore, all chickens slaughtered at 5 weeks were found to have greater contents of linoleic acid (18:2) and polyunsaturated fatty acids (PUFA) and lower atherogenicity and thrombogenicity indices than those slaughtered at 12 weeks (P≤0.05). However, anserine, betaine, and glucose were more concentrated among the lines at 12 weeks than at 5 weeks (P≤0.05). In conclusion, the quality traits of native chickens were distinct by different production stages rather than chicken lines.

• Journal of Life Science
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• v.33 no.1
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• pp.15-24
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• 2023

To examine the antitumor effect of proso millet grains, whether proso millet grains exert apoptotic activity against human cancer cells was investigated. When the cytotoxicity of 80% ethanol (EtOH) extract of proso millet grains was tested against various cancer cells using MTT assay, more potent cytotoxicity was observed against human breast cancer MDA-MB-231 cells than against other cancer cells. When the EtOH extract was evaporated to dryness, dissolved in water, and then further fractionated by sequential extraction using four organic solvents (n-hexane, methylene chloride, ethyl acetate, and n-butanol), the BuOH fraction exhibited the highest cytotoxicity against MDA-MB-231 cells. Along with the cytotoxicity, TUNEL-positive apoptotic nucleosomal DNA fragmentation and several apoptotic responses including BAK/BAX activation, mitochondria membrane potential (Δψm) loss, mitochondrial cytochrome c release into the cytosol, activation of caspase-8/-9/-3, and degradation of poly (ADP-ribose) polymerase (PARP) were detected. However, human normal mammary epithelial MCF-10A cells exhibited a significantly lesser extent of sensitivity compared to malignant MDA-MB-231 cells. Irrespective of Fas-associated death domain (FADD)-deficiency or caspase-8-deficiency, human T acute lymphoblastic leukemia Jurkat cells displayed similar sensitivities to the cytotoxicity of BuOH fraction, excluding an involvement of extrinsic apoptotic mechanism in the apoptosis induction. These results demonstrate that the cytotoxicity of BuOH fraction from proso millet grains against human breast cancer MDA-MB-231 cells is attributable to intrinsic apoptotic cell death resulting from BAK/BAX activation, and subsequent mediation of mitochondrial damage-dependent activation of caspase cascade.