• International Journal of Oral Biology
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• v.42 no.4
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• pp.183-190
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• 2017

Ficus carica L. (common fig), one of the first plants cultivated by humans, originated in the Mediterranean basin and currently grows worldwide, including southwest Asia and South Korea. It has been used as a traditional medicine for treatment of metabolic, cardiovascular, and respiratory diseases as well as hemorrhoids and skin infections. Its pharmacological properties have recently been studied in detail, but research on the anti-cancer effect of its latex has been only been studied on a limited basis on several cell lines, such prostate cancer, breast cancer, and leukemia. In this study, we investigated the anti-cancer activity of the latex of Ficus carica L.and its underlying mechanism in FaDu human hypopharynx squamous carcinoma cells. (See Ed. note above) We confirmed through SDS-PAGE analysis and gelatinolytic activity analysis that the latex of Ficus carica contains cysteine protease ficin. Our data showed that the latex inhibited cell growth in a dose-dependent manner. In addition, the latex treatment markedly induced apoptosis in FaDu cells as determined by FACS analysis, elevated expression level of cleaved caspase-9, -3 and PARP (poly (ADP-ribose) polymerase), and. increased the expression of Bax (pro-apoptotic factor) while decreasing the expression of Bcl-2 (anti-apoptotic factor). Taken together, these results suggested that latex containing the ficin inhibited cell growth and induced apoptosis by caspase and the Bcl-2 family signaling pathway in FaDu human hypopharynx squamous carcinoma cells. These findings point to the potential of latex of Ficus carica to provide a novel chemotherapeutic drug due to its growth inhibition effects and induction of apoptosis in human oral cancer cells.

• Journal of Pharmacopuncture
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• v.18 no.2
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• pp.26-32
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• 2015

Objectives: Rheum undulatum L. has traditionally been used for the treatment of many diseases in Asia. However, its anti-proliferative activity in cancer has still not been studied. In the present study, we investigated the anti-cancer effects of methanol extract of Rheum undulatum L. (MERL) on human adenocarcinoma gastric cell lines (AGS). Methods: To investigate the anti-cancer effect of MERL on AGS cells, we treated the AGS cells with varying concentrations of MERL and performed 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays. Cell cycle analyses, measurements of the mitochondrial membrane potential (MMP), caspase activity assays and Western blots were conducted to determine whether AGS cell death occurred by apoptosis. Results: Treatment with MERL significantly inhibited growth of AGS cells in a concentration dependent manner. MERL treatment in AGS cells leaded to increased accumulation of apoptotic sub G1 phase cells in a concentration dependent manner. In control cultures, 5.38% of the cells were in the sub G1 phase. In MERL treated cells, however, this percentage was significantly increased (9.95% at $70{\mu}g/mL$, 15.94% at $140{\mu}g/mL$, 26.56% at $210{\mu}g/mL$ and 38.08% at $280{\mu}g/mL$). MERL treatment induced the decreased expression of pro-caspase-8 and -9 in a concentration dependent manner, whereas the expression of the active form of caspase-3 was increased. A subsequent Western blot analysis revealed increased cleaved levels of poly (ADP-ribose) polymerase (PARP) protein. Also, treatment with MERL increased the activities of caspase-3 and -9 compared with the control. MERL treatment increased the levels of the pro-apoptotic truncated Bid (tBid) and Bcl2 Antagonist X (Bax) proteins and decreased the levels of the anti-apoptotic B-cell lymphoma 2 (Bcl-2) protein, whose is the stabilization of mitochondria. However, inhibitions of p38, extracellular signal regulated kinases (ERKs) and C-Jun N-terminal kinases (JNK) by MERL treatment did not affect cell death. Conclusion: These results suggest that MERL mediated cell death is associated with an intrinsic apoptotic pathway in AGS cells.

• Journal of Life Science
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• v.29 no.7
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• pp.809-816
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• 2019

The ubiquitous plant metabolite p-coumaric acid (p-CA) has antioxidant and anti-inflammatory properties, but its anti-cancer activity has not been established in gastric cancer cell lines. In this study, we investigated the effects of p-CA on the proliferation and transcriptome profile of SNU16 gastric cancer cells. Treatment with p-CA induced apoptosis of the SNU-16 cells by regulating the expression of pro-apoptotic and anti-apoptotic proteins, such as Bcl-2, poly (ADP-ribose) polymerase (PARP), Bax, procaspase-3, and cleaved-caspase-3. The genes differentially expressed in response to p-CA treatment of the SNU-16 cells were identified by RNA sequencing analysis. Genes regulated by p-CA were involved mainly in the inflammatory response, apoptotic processes, cell cycle, and immune response. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that the phosphatidylinositol-3-kinase-Akt and cancer signaling pathways were altered by p-CA. Protein-protein interaction (PPI) network analysis also revealed that p-CA treatment was correlated with differential expression of genes associated with the inflammatory response and cancer. Collectively, these results suggest that p-CA has potential utility in gastric cancer prevention.

• Korean Journal of Food Science and Technology
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• v.54 no.2
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• pp.134-140
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• 2022

Kelp belongs to the brown algae family and has been reported to exert anti-cancer effects on some cancer types, however studies have not been reported on the anti-cancer effects of kelp extracts on melanoma. In this study, the anti-cancer effects of kelp extract in B16-F0 cells were investigated, and the underlying molecular mechanisms were assessed. Kelp extract was found to inhibit the proliferation of B16-F0 cells, induce cytotoxicity, inhibit cell colony formation, and induce DNA fragmentation and apoptosis. The molecular mechanism was found to involve kelp extract increasing the expression of cytochrome-c and activated caspase-9 in the intrinsic apoptotic pathway. In addition, kelp extract upregulated the expression of Fas-associated protein with death domain and activated caspase-8 in the extrinsic apoptosis pathway. Activation of caspase-9 and caspase-8 by kelp extract induced activation of caspase-3 and cleaved poly adenosine diphosphate-ribose polymerase, consequently inducing apoptosis. These data suggest that kelp extract represents a potential therapeutic agent for melanoma.

• Nutrition Research and Practice
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• v.15 no.3
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• pp.294-308
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• 2021

BACKGROUD/OBJECTIVES: Allomyrina dichotoma larva (ADL), one of the many edible insects recognized as future food resources, has a range of pharmacological activities. In a previous study, an ADL extract (ADLE) reduced the hepatic insulin resistance of high-fat diet (HFD)-induced diabetic mice. On the other hand, the associated molecular mechanisms underlying pancreatic beta-cell dysfunction remain unclear. This study examined the effects of ADLE on palmitate-induced lipotoxicity in a beta cell line of a rat origin, INS-1 cells. MATERIALS/METHODS: ADLE was administered to high-fat diet treated mice. The expression of apoptosis-related molecules was measured by Western blotting, and reactive oxidative stress generation and nitric oxide production were measured by DCH-DA fluorescence and a Griess assay, respectively. RESULTS: The administration of ADLE to HFD-induced diabetic mice reduced the hyperplasia, 4-hydroxynonenal levels, and the number of apoptotic cells while improving the insulin levels compared to the HFD group. Treatment of INS-1 cells with palmitate reduced insulin secretion, which was attenuated by the ADLE treatment. Furthermore, the ADLE treatment prevented palmitate-induced cell death in INS-1 cells and isolated islets by reducing the apoptotic signaling molecules, including cleaved caspase-3 and PARP, and the Bax/Bcl2 ratio. ADLE also reduced the levels of reactive oxygen species generation, lipid accumulation, and nitrite production in palmitate-treated INS-1 cells while increasing the ATP levels. This effect corresponded to the decreased expression of inducible nitric oxide synthase (iNOS) mRNA and protein. CONCLUSIONS: ADLE helps prevent lipotoxic beta-cell death in INS-1 cells and HFD-diabetic mice, suggesting that ADLE can be used to prevent or treat beta-cell damage in glucose intolerance during the development of diabetes.

• Journal of Life Science
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• v.26 no.12
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• pp.1431-1437
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• 2016

Sorghum bicolor L. is one of the important minor cereals in Asia, Africa, and the central United States, and it is considered a rich source of polyphenols, flavonoids, and dietary fiber. However, there is a lack of data on the anti-cancer activity of Sorghum in prostate cancer cells and immune activity in macrophages. This study aims to investigate the potential effects of an ethanol extract of S. bicolor L. (SE) on inducing apoptosis in RC-58T/h/SA#4 cells and immunomodulatory activity in RAW 264.7 cells. SE significantly inhibited the viability of RC-58T/h/SA#4 primary prostate cancer cells in a dose-dependent manner. The morphology of RC-58T/h/SA#4 cells treated with SE was shrunken and involved the formation of an apoptotic body and nuclear condensation. In addition, SE markedly activated caspase-8, -9, and -3; increased the protein levels of Bax, p53, cleaved PARP, and cytosolic cytochrome c; and decreased Bcl-2 protein expression. Furthermore, the inhibition of caspases in RC-58T/h/SA#4 cells with z-VAD-fmk attenuated SE-induced cell growth inhibition. The production of nitric oxide (NO) was also elevated by SE treatment, as revealed by immune response parameters. These results suggest that SE inhibits growth and induces apoptosis in primary human prostate cancer cells in a caspase-dependent manner, and it modulates the immune functions in macrophages. Therefore, Sorghum bicolor L. may be used as a functional food to prevent prostate cancer and enhance immune activity.

• Journal of Life Science
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• v.23 no.5
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• pp.689-697
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• 2013

In the United States, about 40,000 new cases of oral cancer are diagnosed each year and nearly 7,800 patients died from it in 2012. Omega-3 polyunsaturated fatty acids have been found to have anticancer effects in a variety of cancer cell lines and animal models, but their effect in oral cancer remains unclear. This study was designed to examine the effect of docosahexaenoic acid (DHA, a kind of omega-3 fatty acid) on oral cancer cells and the molecular mechanism of its action. We found that exposure of squamous cell carcinoma-4 (SCC-4) and squamous cell carcinoma-9 (SCC-9) human oral cancer cells to DHA induced growth inhibition in a dose- and time-dependent manner. Meanwhile, in addition to the elevated levels of apoptotic markers, such as cleaved PARP, subG1 portion and TUNEL-positive nuclei, DHA led to autophagic vesicle formation and an increase in autophagic flux, indicating the involvement of both apoptosis and autophagy in the inhibitory effects of DHA on oral cancer cells. Further experiments revealed that the apoptosis and autophagy induced by DHA were linked to inhibition of mammalian target of rapamycin (mTOR) signaling by AKT inhibition and AMP-activated protein kinase (AMPK) activation in SCC-9 cells. Together, our results suggest that DHA induces apoptosis- and autophagy-associated cell death through the AMPK/AKT/mTOR signaling pathway in oral cancer cells. Thus, utilization of omega-3 fatty acids may represent a promising therapeutic approach for chemoprevention and treatment of human oral cancer.

• Journal of Food Hygiene and Safety
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• v.34 no.5
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• pp.495-501
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• 2019

Aloin [1,8-Dihydroxy-10-(${\beta}$-D-glucopyranosyl)-3-(hydroxymethyl)-9(10H)-anthracenone], is a natural anthraquinone from aloe. It has been shown to have antioxidant and anticancer effects in various types of human cancer cells, but the anticancer effects of aloin in human colorectal cancer cells HT-29 have not been elucidated. In this study, possible mechanisms by which aloin exerts its apoptotic action in cultured human colorectal cancer HT-29 cells were investigated. The results of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay shows that treatment with aloin (0, 100, 200, 300 and $400{\mu}M$) reduced cell viability in a concentration-dependent manner in HT-29 and showed no effects on cell proliferation in A375SM and AGS cells. In addition, it was confirmed that apoptotic body was significantly increased as shown by 4',6-diamidino-2-phenylindole (DAPI) staining, and increased apoptosis rate by flow cytometry in HT-29 cells treated with aloin (0, 200 and $400{\mu}M$). We confirmed by western blotting that aloin activated Bax (pro-apoptotic), cleaved-poly (ADP-ribose) polymerase (PARP) and caspase-3, -8 and Bcl-2 (anti-apoptotic) were not changed compared with the control. Aloin induced up-regulation of phospho-p38 and down-regulation of phospho-extracellular signal-regulated kinase (ERK)1/2. Therefore, aloin suppressed the growth inhibitory effects by the induction of apoptosis in human colorectal cancer cells and has potential as a cancer preventive medicine.

• Korean Journal of Food Science and Technology
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• v.40 no.2
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• pp.207-214
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• 2008

In Asia Saussurea lappa (SL) has been used as a traditional herbal medicine to treat abdominal pain and tenesmus. Recently, in vitro cell culture studies have shown that SL has anti-ulcer, anti-inflammatory, and anti-tumor properties. To explore its potential chemopreventive and chemotherapeutic effects in colon cancer, we examined whether the hexane extract of SL (HESL) could inhibit the growth of HT-29 human colon cancer cells, and investigated the mechanisms for this effect. The cells were cultured with various concentrations (0-5 ${\mu}g/mL$) of HESL. The results indicated that HESL markedly decreased the numbers of viable HT-29 cells; whereas at the concentration of 5 ${\mu}g/mL$, HESL slightly decreased the viable cell numbers of CCD 1108Sk human skin normal fibroblasts at 72 hr. HESL substantially increased the numbers of cells in the sub G1 phase, and dose-dependently increased apoptotic cell numbers. Western blot analysis of the total cell lysates revealed that HESL increased Bax protein levels, but did not affect Bcl-2 levels. HESL induced the cleavage of poly (ADP-ribose) polymerase and caspases 8, 9, 7, and 3. This study demonstrated that HESL inhibits cell growth and induces apoptosis in HT-29 cells, which may be mediated by its ability to increase Bax levels and activate the caspase pathway. These findings may lead to the development of new therapeutic strategies for colon cancer treatment.

• Journal of Life Science
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• v.29 no.3
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• pp.295-302
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• 2019

Liquiritigenin (LG) is a chiral flavonoid isolated from the roots of licorice. It exhibits multiple biological activities including anti-oxidant, anti-cancer, and anti-inflammatory effects. In particular though, the anti-cancer activity of LG in oral squamous cell carcinoma has yet to be elucidated, and LG-induced apoptosis in oral squamous cell carcinoma remains poorly understood. In the present study, we tested the role of LG in inducing apoptosis in oral squamous cell carcinoma cells. LG treatment of HN22 cells resulted in a dose-dependent inhibition of cell viability as detected by a 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide assay. The induction of apoptosis in terms of Annexin V/7-Aminoactinomycin D staining, sub-G1 population, and multi-caspase activity were assessed with a $Muse^{TM}$ Cell Analyzer. Flow cytometric analysis revealed that LG treatment resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and CDC2 expression in a concentration-dependent manner. It also resulted in significant upregulation of p27. In addition, LG was seen to trigger the generation of reactive oxygen species and induce CCAAT/enhancer-binding protein homologous protein and 78-kDa glucose-regulated protein in concentration-dependent upregulation. The LG treatment of HN22 cells led to a loss of mitochondrial membrane potential (${\Delta}{\Psi}m$); it also reduced the levels of anti-apoptotic protein and increased the expression of apoptotic protease activating factor-1, cleaved poly (ADP-ribose)polymerase and Bax. Overall, our results indicate that the pro-apoptotic effects of LG in HN22 cells depend on the activation of both intrinsic and extrinsic signaling pathways. Thus, our results suggest that LG constitutes a natural compound with a potential role as an anti-tumor agent in oral squamous cell carcinoma.