• Journal of Life Science
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• v.15 no.3 s.70
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• pp.397-405
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• 2005

Sulforaphane, an isothiocyanate derived from hydrolysis of glucoraphanin in broccoli and other cruciferous vegetables, was shown to induce phase II detoxification enzymes and inhibit chemically induced mammary tumors in rodents. Recently, sulforaphane is known to induce cell cycle arrest and apoptosis in human cancer cells, however its molecular mechanisms are poorly understood. In the present study, we demonstrated that sulforaphane acted to inhibit proliferation and induce morphological changes of human cervical carcinoma HeLa cells. Treatment of HeLa cells with $10{\mu}M\;or\;15{\mu}M$ sulforaphane resulted in significant G2/M cell cycle arrest as determined by flow cytometry. Moreover, $20{\mu}M$ sulforaphane significantly induced the population of sub-G1 cells (9.83 fold of control). This anti-proliferative effect of sulforaphane was accompanied by a marked inhibition of cyclin A and cyclin-dependent kinase (Cdk)4 protein and concomitant induction of Cdc2, Cdk inhibitor p16 and p21. However, sulforaphane did not affect the levels of cyelooxygenases and telomere-regulatory gene products. Although further studies are needed, the present work suggests that sulforaphane may be a potential chemoprevetive/ chemotherapeutic agent for the treatment of human cancer cells.

• Journal of Life Science
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• v.20 no.10
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• pp.1532-1537
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• 2010

This study compared the inhibitory effects of methanol extracts from yellow and black soybeans (black soybean, Seomoktae and Seoritae) on mutagenicity using the Ames test and growth of human cancer cells (AGS human gastric adenocarcinoma, HT-29 human colon cancer, Hep 3B hepatocellular carcinoma cells). In the Ames test system using Salmonella typhimurium TA100, aflatoxin $B_1$ ($AFB_1$)-induced mutagenicity was significantly inhibited by treatments with the methanol extracts from either yellow or black soybeans in a dose dependent manner (p<0.05). The methanol extracts from various black soybeans tended to have a greater inhibitory effect compared to those from yellow soybeans. As for N-methyl-N'-nitro-N-nitrosoguamidine (MNNG)-induced mutagenicity, the methanol extracts (5 mg/assay) from black soybean, Seomoktae and Seoritae showed 51%, 61% and 53% inhibitory rates, respectively, indicating that Seomoktae, a type of black soybean, had a stronger antimutagenic activity against mutagens (both $AFB_1$ and MNNG). Methanol extracts from black soybeans showed an inhibitory rate of greater than 50% on the growth of human cancer cells (AGS, HT-29 and Hep 3B) and the inhibition was more effective in the methanol extract from Seomoktae. Our results suggested that the methanol extracts from black soybeans showed stronger inhibitory effects on mutagenicity and growth of cancer cells than those from yellow soybean. It is concluded that intake of black soybean can be recommended for improving health.

• Journal of Life Science
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• v.27 no.9
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• pp.1020-1030
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• 2017

Epidemiology studies have reported a reduced incidence of colon cancer among populations that consume a large quantity of ${\omega}3-polyunsaturated$ fatty acids (${\omega}3-PUFAs$) of marine origin. Herein, we demonstrated a mechanism of anticancer action of ${\omega}3-PUFAs$, showing that they suppressed invasion and tumorigenicity in colon cancer cells. Docosahexaenoic acids (DHA) inhibited the cell growth of HT29 cells. This action likely involved apoptosis, given that the DHA treatment increased the cleaved form of PARP and sub G1 cells. Moreover, the invasiveness of HT29 cells was inhibited following DHA treatment, whereas arachidonic acid (AA) had no effect. The levels of Matrix-metalloproteinase-9 (MMP-9) and MMP-2 mRNA decreased after DHA pretreatment. DHA treatment inhibited MMP-9 and MMP-2 promoter activities and reduced VEGF promoter activity. DHA pretreatment also inhibited the activities of prostaglandin-2 (PGE2)-induced MMPs and the VEGF promoter. Cyclooxygenase-2 (COX-2) overexpression increased the activity of MMPs and that of the Vascular endotherial growth factor (VEGF) promoter in HT29 cells, and DHA inhibited NF-kB and COX-2 promoter reporter activities. As shown by in vivo experiments, when mouse colon cancer cells (MCA38) were implanted into Fat-1 and wild-type mice, both the tumoral size and volume were dramatically inhibited in Fat-1 transgenic mice. Furthermore, TUNEL-positive cells increased in tumors from Fat-1 mice compared with wild mice. In immunohistochemistry, the intensity of CD31 in Fat-1 tumors was weaker. These findings suggest that ${\omega}3-PUFAs$ may inhibit tumorigenicity and angiogenesis as well as cancer cell invasion by suppression of COX-2, MMPs and VEGF via the reduction of NF-kB in colon cancer.

• Journal of Life Science
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• v.18 no.3
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• pp.336-343
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• 2008

Histone deacetylases (HDACs) inhibitors have emerged as the accessory therapeutic agents for various human cancers, since they can block the activity of specific HDACs, restore the expression of some tumor suppressor genes and induce cell differentiation, cell cycle arrest and apoptosis in vitro and in vivo. In the present study, we investigated that the effect of trichostatin A (TSA), an HDAC inhibitor, on the cell growth and apoptosis, and its effect on the nuclear factor-kappaB $(NF-{\kappa}B)$ activity in 267B1 human prostate epithelial cells. Exposure of 267B1 cells to TSA resulted in growth inhibition and apoptosis induction in and dose-dependent manners as measured by fluorescence microscopy, agarose gel electrophoresis and flow cytometry analysis. TSA treatment inhibited the levels of IAP family members such as c-IAP-1 and c-IAP-2 and induced the proteolytic activation of caspase-3, -8 and -9, which were associated with concomitant degradation of poly (ADP-ribose)-polymerase, ${\beta}-catenin$ and laminin B proteins. The increase in apoptosis by TSA was connected with the translocation of $NF-{\kappa}B$ from cytosol to nucleus, increase of the DNA binding as well as promoter activity of $NF-{\kappa}B$, and degradation of cytosolic inhibitor of KappaB $(I{\kappa}B)-{\alpha}$ protein. We therefore concluded that TSA demonstrated anti-proliferative and apoptosis-inducing effects on 267B1 cells in vitro, and that the activation of caspases and $NF-{\kappa}B$ may play important roles in its mechanism of action. Although further studies are needed, these findings provided important insights into the possible molecular mechanisms of the anti-cancer activity of TSA.

• Journal of Life Science
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• v.23 no.8
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• pp.984-988
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• 2013

Sparassis crispa is an edible mushroom with medicinal properties that contains more than 40% ${\beta}$-glucan. The role of S. crispa in regulating the functional activation of macrophages has yet to be fully elucidated. The objective of this study was to investigate the molecular mechanism underlying the immune-stimulatory function of S. crispa soluble ${\beta}$-glucan and extracts on macrophages. In this study, we showed that S. crispa soluble ${\beta}$-glucan was able to stimulate TNF-${\alpha}$ and IL-$1{\beta}$ production through NF-${\kappa}B$ activation in Raw 264.7 cells. We also showed that S. crispa extracts could not only enhance TNF-${\alpha}$ production in Raw 264.7 cells, but also suppress tumor growth in vivo. All of our results suggest that S. crispa could be developed as a promising immunostimulatory principle, applicable to cancer patients.

• Journal of Life Science
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• v.30 no.5
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• pp.460-467
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• 2020

Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancers in the word. Although radiation and chemotherapy are generally effective, there are various side effects that greatly limit the effectiveness of these treatments. Therefore, traditional herbs may have potential as important resources for the discovery of liver cancer therapeutics. In this study, we selected three Korean herbal medicine formulas from the Donguibogam, namely Bigihwan (BGH), Daechilgithang (DCGT), and Mokwhyangbinranghwan (MHBRH), and evaluated their anti-cancer effects on HCC cells. According to our results of three ethanol extracts, BGH was more effective at suppressing HCC growth than DCGT or MHBRH. Furthermore, flow cytometry analysis showed that inhibition of HCC proliferation by the three extracts was associated with the induction of apoptosis and autophagy. In particular, BGH significantly increased mitochondrial impairment and showed the possibility of inducing mitophagy in comparison with the other two extracts. BGH prominently upregulated the levels of microtubule-associated protein light chain-3 which was accompanied by a decrease in the expression of anti-apoptotic Bcl-2 without altering the expression of pro-apoptotic Bax. In addition, the levels of PTEN-induced kinase 1 were also markedly increased in BGH-treated HCC cells. Moreover, autophagy blocking improved cell viability and reduced apoptosis after the three treatments, indicating that autophagy by these extracts enhances HCC cells against cytotoxicity. In conclusion, our findings show that BGH demonstrates the highest anti-cancer activity among the three formulas and inhibits the proliferation of HCC cells through autophagy induction.

• Biomolecules & Therapeutics
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• v.30 no.6
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• pp.553-561
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• 2022

Chronic myeloid leukemia (CML) is a slowly progressing hematopoietic cell disorder. Sphingosine kinase 1 (SPHK1) plays established roles in tumor initiation, progression, and chemotherapy resistance in a wide range of cancers, including leukemia. However, small-molecule inhibitors targeting SPHK1 in CML still need to be developed. This study revealed the role of SPHK1 in CML and investigated the potential anti-leukemic activity of hirsuteine (HST), an indole alkaloid obtained from the oriental plant Uncaria rhynchophylla, in CML cells. These results suggest that SPHK1 is highly expressed in CML cells and that overexpression of SPHK1 represents poor clinical outcomes in CML patients. HST exposure led to G2/M phase arrest, cellular apoptosis, and downregulation of Cyclin B1 and CDC2 and cleavage of Caspase 3 and PARP in CML cells. HST shifted sphingolipid rheostat from sphingosine 1-phosphate (S1P) towards the ceramide coupled with a marked inhibition of SPHK1. Mechanistically, HST significantly blocked SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways. In addition, HST can be docked with residues of SPHK1 and shifts the SPHK1 melting curve, indicating the potential protein-ligand interactions between SPHK1 and HST in both CML cells. SPHK1 overexpression impaired apoptosis and proliferation of CML cells induced by HST alone. These results suggest that HST, which may serve as a novel and specific SPHK1 inhibitor, exerts anti-leukemic activity by inhibiting the SPHK1/S1P/S1PR1 and BCR-ABL/PI3K/Akt pathways in CML cells, thus conferring HST as a promising anti-leukemic drug for CML therapy in the future.

• Journal of the Korean Society of Food Science and Nutrition
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• v.33 no.3
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• pp.480-486
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• 2004

Despite many therapeutic advances in the understanding of the processes in carcinogenesis, overall mortality statistics are unlikely to change until there is reorientation of the concepts for the use of natural products as new anticarcinogenic agents. In this study, we investigated the anticarcinogenic activity, antioxidant and DPPH scavenging activity of Sargassum fulvellum (SF). SF was extracted with methanol, which was further fractionated into five different types: hexane (SFMH), ethylether (SFMEE), ethyl acetate (SFMEA), butanol (SFMB) and aqueous (SFMA) partition layers. We determined the cytotoxic effect of these layers on human cancer cells by MTT assay. Among various partition layers of SF, at starting concentration of 100 $\mu\textrm{g}$/mL, SFMEE showed very high cytotoxicity which were 92, 90 and 84% and kept high throughout 5 concentration levels sparsed by 100 $\mu\textrm{g}$/mL against all three human cancer cell lines: HepG2, HT-29 and HeLa. SFMEA showed a low cytotoxicity at the beginning concentration level, but as the concentration became denser, growth inhibition effect of cancer cell lines started to increase and at 500 $\mu\textrm{g}$/mL, it hit the highest, which were 91, 96 and 98% against the same three cell lines as above. We observed QR induced effect in all fraction layers of SF. SFMEE showed similar tendensy of QR induced effect as did against cytotoxicity. The QR induced effect of SFMEE on HepG2 cells at 25 $\mu\textrm{g}$/mL concentration indicated 3 times higher than the control value of 1.0 and SFMH tended to be concentration-dependent on HepG2 cells. At 100 $\mu\textrm{g}$/mL, the QR induced effects resulted a ratio, which was 2.5 times higher than the control value. In search for antioxidation effects of SF extract and partition layer, the reducing activity on the 1, 1-diphenyl-2-picryl hydrazyl (DPPH) radical scavenging potential was sequentially screened. The SFM has similar antioxidant activity as to BHT and vitamin C groups.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.5
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• pp.921-927
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• 2001

This study was performed to investigated the effects on the cytotoxicity and antigenotoxicity of Cordyceps militaris extracts on the human cancer cell lines. The ethanol extract and five fractions which were hexane, chloroform, ethylacetate, butanol and aqueous were screened for crytotoxicity on human lung carcinoma(A549). human breast adenocarcinoma (MCF-7) human epitheloid carcinoma(HeLa), human fibrosarcoma(HT1080) human hepatocellular carcinoma(Hep3B), human gastric carcinoma(KATOIII) and chronic myelogenous leukemia(K562) cell by SRB and MTT assays. The results showed that growth inhibition rates of the human cancer cell in the presence of Cordyceps militaris were inhibited with increasing concentration of the extract. The ethanol extract from Cordyceps militaris had strong inhibitory effects in1 mg/mL treatment by SRB assay , showing 89.4%, 85.7%, 72.9% and 65.5% inhibition in HT1080, HeLa, Hep3B and A549, respectively. The treatment of 1 mg/mL hexane fraction by SRB assay had the strongest cytotoxicity with 97.0% on HT1080 followed by MCF-7(92.9%) and HeLA(90.3%). The inhibition ration on KATOIII by MTT assay was much higher in the butanol (83.7%) and aqueous (80.4%) than in the ethanol extract (61.5%) And also, K562 showed similar tendency with KATOIII. The effects of Cordyceps militaris extracts on the frequencies of micronucleated polychromatic erythrocytes (MNPCEs) induced by N-methyl-N-nitro-N-nitrosoguanidime(MNNG) were investigated in the bone-marrow cells of ICR male mice. The amount of 10, 20, 40 and 80 mg/kg of each extract were administered to animals immediately after injection of MNNG, and the exposure time was 36 hours. Significant reductions(p<0.05) with 39.7%, 52.7%, 71.4% and 83.9% were observed in the frequencies of MNPCE when 10, 20, 40 and 80 mg/kg of the hexane fraction of Coryceps militarus extracts were given to the mice.

• Journal of Life Science
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• v.25 no.2
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• pp.249-255
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• 2015

Schisandrae fructus [Schizandra chinensis (Turcz.) Baillon] is a medicinal herb widely used for treating various inflammatory and immune diseases in East Asian countries. The Schisandrae Semen essential oil (SSeo) from this plant has pharmacological activities, including antioxidant, antimicrobial, and antitumoral activities. Nevertheless, the biological activities and underlying molecular mechanisms of the potential anti-cancer effects of this oil remain unclear. In the present study, we investigated the potential inhibition of apoptosis signaling pathways by SSeo in human leukemia U937 cells and evaluated the underlying molecular mechanism. Exposure to SSeo resulted in a concentration-dependent growth inhibition due to apoptosis, which was verified by DNA fragmentation, the presence of apoptotic bodies, and an increase in the sub-G1 ratio. Induction of apoptotic cell death by SSeo was correlated with the down-regulation of members of the inhibitor of apoptosis protein (IAP) family (including X-linked inhibitor of apoptosis protein (XIAP), cIAP-1, and surviving) and anti-apoptotic Bcl-2, and with up-regulation of death receptor (DR) 4 and DR5, depending on dosage. SSeo treatment also induced Bid truncation, mitochondrial dysfunction, proteolytic activation of caspase-3, -8 and -9, and concomitant degradation of activated caspase-3 target proteins such as poly (ADP-ribose) polymerase. Taken together, these findings suggest that SSeo may be a potential chemotherapeutic agent for use in the control of human leukemia cells. Further studies are needed to identify its active compounds.