• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.863-868
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• 2015

Background: Artemisia species are important medicinal plants throughout the world. The present in vitro study, using a sesquiterpene lactone-bearing fraction prepared from Artemisia khorassanica (SLAK), sought to investigate anti-cancer properties of this plant and elucidate potential underlying mechanisms for the effects. Materials and Methods: Anti-cancer potential was evaluated by toxicity against human melanoma and fibroblast cell lines. To explore the involved pathways, pattern of any cell death was determined using annexin-V/PI staining and also the expression of Bax and cytochrome c was investigated by Western blotting. Results: The results showed that SLAK selectively caused a concentration-related inhibition of proliferation of melanoma cells that was associated with remarkable increase in early events and over-expression of both Bax and cytochrome c. Conclusions: The current experiment indicates that Artemisia may have anti-cancer activity. We anticipate that the ingredients may be employed as therapeutic candidates for melanoma.

• Journal of Ginseng Research
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• v.47 no.4
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• pp.572-582
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• 2023

Background: Free fatty acid-induced lipotoxicity is considered to play an important role in pancreatic β-cell dysfunction. The effect of ginsenosides on palmitic acid-induced pancreatic beta-cells cell death and failure of glucose-stimulated secretion of insulin (GSIS) was evaluated in this study. Methods: Enzyme-linked immunosorbent assay kit for a rat insulin was used to quantify glucose-stimulated insulin secretion. Protein expression was examined by western blotting analysis. Nuclear condensation was measured by staining with Hoechst 33342 stain. Apoptotic cell death was assessed by staining with Annexin V. Oil Red O staining was used to measure lipid accumulation. Results: We screened ginsenosides to prevent palmitic acid-induced cell death and impairment of GSIS in INS-1 pancreatic β-cells and identified protopanaxadiol (PPD) as a potential therapeutic agent. The protection effect of PPD was likely due to a reduction in apoptosis and lipid accumulation. PPD attenuated the palmitic acid-induced increase in the levels of B-cell lymphoma-2-associated X/B-cell lymphoma 2, poly (ADP-ribose) polymerase and cleaved caspase-3. Moreover, PPD prevented palmitic acid-induced impairment of insulin secretion, which was accompanied by an increase in the activation of phosphatidylinositol 3-kinase, peroxisome proliferator-activated receptor γ, insulin receptor substrate-2, serine-threonine kinase, and pancreatic and duodenal homeobox-1. Conclusion: Our results suggest that the protective effect of PPD on lipotoxicity and lipid accumulation induced by palmitic acid in pancreatic β-cells.

• Biomolecules & Therapeutics
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• v.20 no.4
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• pp.393-398
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• 2012

Recently, we reported that defective autophagy may contribute to the inhibition of the growth in response to PP2 (4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolo[3,4-d]pyrimidine), a selective SFK inhibitor, in multidrug-resistant v-Ha-ras-transformed NIH 3T3 cells (Ras-NIH 3T3/Mdr). In this study, we demonstrated that PP2 induces LC3 conversion via a mechanism that is uncoupled from autophagy and increases apoptosis in Ras-NIH 3T3/Mdr cells. PP2 preferentially induced autophagy in Ras-NIH 3T3 cells rather than in Ras-NIH 3T3/Mdr cells as determined by LC3-I to LC3-II conversion and GFP-LC3 fluorescence microscopy. Beclin 1 knockdown experiments showed that, regardless of drug resistance, PP2 induces autophagy via a Beclin 1-dependent mechanism. PP2 induced a conformational change in Beclin 1, resulting in the enhancement of the pro-autophagic activity of Beclin 1, in Ras-NIH 3T3 cells. Further, PI3K inhibition induced by wortmannin caused a significant increase in apoptosis in Ras-NIH 3T3 cells, as demonstrated by flow cytometric analysis of Annexin V staining, implying that autophagy inhibition through PI3K increases apoptosis in response to PP2 in Ras-NIH 3T3 cells. However, despite the fact that wortmannin abrogates PP2-induced GFP-LC3 punctae formation, some LC3 conversion remains in Ras-NIH 3T3/Mdr cells, suggesting that LC3 conversion may occur in an autophagy-independent manner. Taken together, these results suggest that PP2 induces LC3 conversion independent of PI3K, concomitant with the uncoupling of LC3 conversion from autophagy, in multidrug-resistant cells.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.15
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• pp.6753-6759
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• 2015

Background: Loss of function of the p53 gene is implicated in defective apoptotic responses of tumors to chemotherapy. Although the pro-apoptotic roles of eugenol and capsaicin have been amply reported, their dependence on p53 for apoptosis induction in gastric cancer cells is not well elucidated. The aim of the study was to elucidate the role of p53 in the induction of apoptosis by eugenol and capsaicin in a human gastric cancer cell line, AGS. Materials and Methods: AGS cells were incubated with or without various concentrations of capsaicin and eugenol for 12 hrs, in the presence and absence of p53 siRNA. Cell cycling, annexin V and expression of apoptosis related proteins Bax, Bcl-2 ratio, p21, cyt c-caspase-9 association, caspase-3 and caspase-8 were studied. Results: In the presence of p53, capsaicin was a more potent pro-apoptotic agent than eugenol. However, silencing of p53 significantly abrogated apoptosis induced by capsaicin but not that by eugenol. Western blot analysis of pro-apoptotic markers revealed that as opposed to capsaicin, eugenol could induce caspase-8 and caspase-3 even in the absence of p53. Conclusions: Unlike capsaicin, eugenol could induce apoptosis both in presence and absence of functional p53. Agents which can induce apoptosis irrespective of the cellular p53 status have immense scope for development as potential anticancer agents.

• Natural Product Sciences
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• v.16 no.2
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• pp.88-92
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• 2010

We verified that the apoptosis activities were examined by DNA fragmentation, flow cytometric analysis with annexin V staining, activation of caspase-3, and cytochrome c release. In the result, $\alpha$- and $\beta$-eudesmol induced DNA fragmentation in HL-60 cells at a concentration of $80\;{\mu}M$, respectively. Additionally, pro-apoptotic cells sorted by flow cytometry analysis were detected in HL-60 cells to 31.77 and 29.67% with $\acute{a}$- and $\beta$-eudesmol of $80\;{\mu}M$. Thus, both $\alpha$- and $\beta$-eudesmol exerted caspase-3 activation and cytochrome c release at $80\;{\mu}M$ in HL-60 cells. These results are firstly reported that the sesquiterpenes, $\alpha$- and $\beta$-eudesmol are apoptosis inducers through mitochondria-dependent caspase cascade in HL-60 cells.

• Biomolecules & Therapeutics
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• v.27 no.2
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• pp.210-215
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• 2019

Colorectal cancer is one of the leading causes of cancer related death due to a poor prognosis. In this study, we investigated the effect of Gomisin G on colon cancer growth and examined the underlying mechanism of action. We found that Gomisin G significantly suppressed the viability and colony formation of LoVo cells. Gomisin G reduced the phosphorylation level of AKT implying that Gomisin G suppressed the PI3K-AKT signaling pathway. Gomisin G also induced apoptosis shown by Annexin V staining and an increased level of cleaved poly-ADP ribose polymerase (PARP) and Caspase-3 proteins. Furthermore, Gomisin G remarkably triggered the accumulation of cells at the sub-G1 phase which represents apoptotic cells. In addition, the level of cyclin D1 and phosphorylated retinoblastoma tumor suppressor protein (Rb) was also reduced by the treatment with Gomisin G thus curtailing cell cycle progression. These findings show the suppressive effect of Gomisin G by inhibiting proliferation and inducing apoptosis in LoVo cells. Taken together, these results suggest Gomisin G could be developed as a potential therapeutic compound against colon cancer.

• Korean Journal of Veterinary Research
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• v.62 no.1
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• pp.3.1-3.7
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• 2022

Disulfiram (DSF) is a marketed drug to treat patients with alcohol dependence by inhibiting aldehyde dehydrogenase. Over the last few decades, DSF has been shown to have anticancer effects through different mechanisms. Moreover, this effect can be elevated when used with copper (Cu). Subsequent studies have been conducted on various cancers, but few on lymphoma. This study investigated the anticancer effects of DSF on lymphoma and how this effect changed when treated with Cu. DSF synergistically decreased the metabolic activity of EL4 lymphoma cells when combined with Cu. At 1 µM of DSF alone, the metabolic activity of EL4 cells decreased by 49% compared to the control, whereas it decreased by 87% with a DSF + CuCl₂ treatment. Rhodamine 123 and 2',7'-dichlorofluorescein diacetate staining showed that DSF induced the reduction of the mitochondrial membrane potential and promoted the production of reactive oxygen species. In particular, the combined treatment of DSF + Cu induced cell death based on multiple assays, including annexin V-fluorescein isothiocyanate/propidium iodide staining. Overall, DSF has anticancer effects on lymphoma cells and exhibits synergistic effects when combined with Cu. This study provides some valuable information to broaden the use of DSF in clinics and basic research.

• Journal of Applied Biological Chemistry
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• v.54 no.1
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• pp.15-20
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• 2011

Red ginseng is one of the most popular traditional medicines in Korea. In this study, we developed a new technique in which ethanol extract of $\underline{r}$ed $\underline{g}$inseng (HRG) was exposed to the $Co^{60}$ gamma radiation ranging from 1~5 kGy. The irradiated HRG (IHRG) were analyzed by high performance liquid chromatography (HPLC) to determine any compositional changes of ginsenosides due to irradiation. No appreciable difference was observed in the HPLC pattern of ginsenosides of HRG. Using MTT assay, the cytotoxicity effect was significantly increased by IHRG compared to HRG. The $LD_{50}$ concentration was $30{\mu}g/mL$ for IHRG-1 (1 kGy), and $15{\mu}g/mL$ for IHRG-5 (5 kGy). The evidences of apoptosis, such as nuclei cleavage and Annexin V staining, were observed in the human prostate cancer PC-3 cells treated with the IHRG. Additionally, the level of reactive oxygen species (ROS) was apparently elevated by IHRG. We also studied the inhibitory effect of IHRG on the growth rate of tumor xenografts in BALB/c male mice. The tumor growth rates were inhibited by 56.9 and 76.1% in mice treated with 10 mg/kg of IHRG-1 and IHRG-5, respectively, compared with control group (21.1%). These results suggest that some biologically active and soluble components in HRG can be more effectively enhancement of anti-tumor effects using irradiation.

• Journal of Applied Biological Chemistry
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• v.63 no.2
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• pp.147-152
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• 2020

Farrerol is a flavanone isolated from the traditional Chinese herb 'Man-shan-hong' (Rhododendron dauricum L.). Farrerol has been reported to have various bioactivities including anti-oxidant, anti-inflammation, and anti-fungal. However, anti-cancer effect of farrerol has not yet been reported in MCF-7 breast cancer cells. In the present study, we investigated the anti-cancer effect of farrerol on MCF-7 cells. Farrerol decreased viability and induced apoptosis of MCF-7 cells in a dose dependent manner. Ferrerol exhibited a significant anti-proliferation effect with a half-maximal inhibitory concentration (IC₅₀) values of 145.04±1.4 μM in MTT assay, when MCF-7 cells were treated with ferrerol for 48 h. Also, ferrerol induced apoptotic bodies of MCF-7 cells as evaluated by TUNEL assay and Annexin V/PI staining using FACS. By mechanism of action, ferrerol regulated the activation of p38 mitogen-activated protein kinase and altered the expression level of BAX, Bcl-2, and Poly ADP Ribose Polymerase in MCF-7 cells. In summary, our finding demonstrated that ferrerol has anti-cancer effect through regulating the activation and expression of apoptosis-related proteins in MCF-7 cells.

• Journal of Life Science
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• v.24 no.5
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• pp.467-475
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• 2014

Sea buckthorn (Hippophae rhamnoides L.) is a well-known and rich source of biologically active compounds, such as flavonoids, carotenoids, steroids, vitamins, tannins, and oleic acid. The effects of sea buckthorn fruit extract (SBFE) on ultraviolet (UV)-induced cell death was investigated in SK-MEL-2 cells cotreated with UV and a low concentration (LoC), medium concentration (MeC), or high concentration (HiC) of SBFE. Cell viability gradually decreased in accordance with an increase in the UV dose. The cell viability of the UV+SBFE cotreated cells increased significantly compared to that of UV+vehicle-treated cells during the application of an appropriate UV radiation dose (400 mJ). In addition, the number of 4',6-diamidino-2-phenylindole (DAPI), propidium iodine (PI)-, and annexin V-stained apoptotic cells was higher in the UV+vehicle-treated cells than in the UV untreated cells. The decrease of apoptotic cell numbers varied in each treated group, but it was most significant in the SBFE-treated group. The number of PI-stained cells dramatically decreased in accordance with the concentration of SBFE, and the maximum decrease was detected in the UV+HiC-treated group. In addition, Bax expression increased and Bcl-2 expression decreased in the SBFE-treated group compared with the UV-only treated group. The level of caspase-3 remained constant in all the groups. These results suggest that SBFE may contribute to a recovery from UV-induced cell death through the regulation of apoptotic protein expression and that it may have potential therapeutic utility in ameliorating UV-induced skin ageing.