• Title/Summary/Keyword: HCT116 cells

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Apoptotic Effects and Cell Cycle Arrest Effects of Extracts from Cnidium monnieri (L.) Cusson through Regulating Akt/mTOR/GSK-3β Signaling Pathways in HCT116 Colon Cancer Cells (HCT116 대장암세포에서 AKT/mTOR/GSK-3β 신호경로 조절을 통한 벌 사상자 추출물(CME)의 apoptosis 및 cell cycle arrest 효과)

  • Lim, Eun Gyeong;Kim, Guen Tae;Kim, Bo Min;Kim, Eun Ji;Ha, Sung Ho;Kim, Sang-Yong;Kim, Young Min
    • Journal of Life Science
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    • v.26 no.6
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    • pp.663-672
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    • 2016
  • The Cnidium monnieri (L.) Cusson is an annual plant distributed in China and Korea. The fruit of C. monnieri is used as a medicinal herb that is effective for the treatment of carbuncle and pain in female genitalia. However, the anti-cancer effects of CME have not yet been reported. In this study, we assessed the apoptotic effects and cell cycle arrest effects of ethanol extracts from C. monnieri on HCT116 colon cancer cells. The results of an MTT assay and LDH assay demonstrated a decrease in cell viability and the cytotoxic effects of CME. In addition, the number of apoptotic body and the apoptotic rate were increased in a dose-dependent manner through Hoechst 33342 staining and Annexin V-PI double staining. In addition, cell cycle arrest occurred at the G1 phase by CME. Protein kinase B (Akt) plays an important role in cancer cell survival, growth, and division. Akt down-regulates apoptosis-mediated proteins, such as mammalian target of rapamycin (mTOR), p53, and Glycogen Synthase kinase-3β (GSK-3β). CME could regulate the expression levels of p-Akt, p-mTOR, p-GSK-3β, Bcl-2 family members, caspase-3, and PARP. Furthermore, treatment with CME, LY294002 (PI3K/Akt inhibitor), BIO (GSK-3β inhibitor), and Rapamycin (mTOR inhibitor) showed that apoptotic effects occurred through the regulation of the AKT/mTOR/GSK-3β signaling pathway. Our results demonstrated CME could induce apoptosis and cell cycle arrest in HCT116 colon cancer cells.

Promoter Activity of the Long Terminal Repeats of Porcine Endogenous Retroviruses of the Korean Domestic Pig

  • Ha, Hong-Seok;Huh, Jae-Won;Kim, Dae-Soo;Kang, Dong-Woo;Cho, Byung-Wook;Kim, Heui-Soo
    • Molecules and Cells
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    • v.24 no.1
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    • pp.148-151
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    • 2007
  • Porcine endogenous retroviruses (PERVs) in the pig genome represent a potential risk of infection in pig-to-human transplantation and are transmitted vertically. The solitary long terminal repeat (LTR) elements of the PERVs affect the replication properties of the individual viruses via their repeat sequences and by encoding a set of specific transcription factors. We examined the promoter activities of solitary LTR elements belonging to the PERV-A and -B families of the Korean domestic pig (KDP) using luciferase reporters. Three of the LTR structures (of PERV-A5-KDP, PERV-A7-KDP, PERV-A8-KDP) had different promoter activities in human HCT116 cells and monkey Cos7 cells, and potential negatively and positively acting regions affecting transcription were identified by deletion analysis. These data suggest that specific sequences in the U3 region of a given LTR element can affect the activities of promoter or enhancer elements in the PERV.

Role of p53-dependent PI3K in Radioresistance of Colon Cancer Cells (대장암 세포의 방사선저항성에 대한 p53의존성 PI3K의 역할)

  • Lee, Heui-Kwan;Kim, Jong-Suk;Kwon, Hyoung-Cheol
    • Journal of Food Hygiene and Safety
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    • v.25 no.3
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    • pp.258-262
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    • 2010
  • Radiotherapy is one of the major therapies for cancer treatment. p53 acts as a central mediator of the cellular response to stressful stimuli, such as radiation. Recently it has been known that activation of the phosphatidylinositol-3-kinase (PI3K) pathway is associated with radioresistance. In this study, we investigated whether X-irradiation up-regulates PI3K in a p53-dependent manner in human colon cancer cells. In order to study this phenomenon, we have treated p53-wild type and p53-mutant type HCT116 cells with X-ray. Treatment of wild type HCT116 cells with 8 Gy resulted in a marked increase in PI3K (p85), which paralleled an increase in PTEN, a counterpart of PI3K. However, these effects of X-rays in the p53-mutant cells were not observed. These results suggest that the X-irradiation-induced up-regulation of PI3K/PTEN pathway is p53-dependent.

Effects of Purple Kohlrabi (Brassica oleracea var. gongylodes) Flesh and Peel Ethanol Extracts on the Antioxidant Activity and Antiproliferation of Human Cancer Cells (자색 콜라비 가식부와 껍질 에탄올 추출물의 항산화 활성 및 암세포 증식 억제효과)

  • Yang, Myung-Ja;Cha, Seon-Suk;Lee, Jae-Joon
    • The Korean Journal of Community Living Science
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    • v.26 no.2
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    • pp.405-414
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    • 2015
  • This study examines the effects of purple Kohlrabi fresh and peel ethanol extracts on the antioxidative activity and antiproliferation of human cancer cells (Hep G2 human liver, HCT-116 human colon, and A549 human lung cancer cells.) The total flavonoid and anthocyanin content of purple Kohlrabi ethanol extracts were much greater in the peel than in the flesh. The DPPH radical scavenging activity and antioxidative index of purple Kohlrabi peel extracts were similar to those of the BHA and the BHT. Antiproliferation effects of purple Kohlrabi peel extracts on human cancer cells (Hep G2, HCT-116, and A549) strengthened in a dose-dependent manner. In particular, the antiproliferation activity of purple Kohlrabi peel extracts exceeded 40% in colon cancer cells. These results indicate that the purple Kohlrabi peel may contain bioactive compounds such as flavonoids as well as anthocyanin and that these compounds may facilitate cancer prevention.

The Nedd8-activating enzyme inhibitor MLN4924 suppresses colon cancer cell growth via triggering autophagy

  • Lv, Yongzhu;Li, Bing;Han, Kunna;Xiao, Yang;Yu, Xianjun;Ma, Yong;Jiao, Zhan;Gao, Jianjun
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.6
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    • pp.617-625
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    • 2018
  • Neddylation is a post-translational protein modification process. MLN4924 is a newly discovered pharmaceutical neddylation inhibitor that suppresses cancer growth with several cancer types. In our study, we first investigated the effect of MLN4924 on colon cancer cells (HCT116 and HT29). MLN4924 significantly inhibited the neddylation of cullin-1 and colon cancer cell growth in a time and dose-dependent manner. MLN4924 induced G2/M cell cycle arrest and apoptosis in HCT116 and HT29 cells. Moreover, MLN4924 also triggered autophagy in HCT116 and HT29 cells via suppressing the PI3K/AKT/mTOR pathway. Inhibiting autophagy by autophagy inhibitor 3-MA or ATG5 knockdown reversed the function of MLN4924 in suppressing colon cancer cell growth and cell death. Interestingly, MLN4924 suppresses colon cell growth in a xenograft model. Together, our finding revealed that blocking neddylation is an attractive colon cancer therapy strategy, and autophagy might act as a novel anti-cancer mechanism for the treatment of colon cancer by MLN4924.

Fentanyl Increases Colorectal Carcinoma Cell Apoptosis by Inhibition of NF-κB in a Sirt1-dependent Manner

  • Zhang, Xiu-Lai;Chen, Min-Li;Zhou, Sheng-Li
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.10015-10020
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    • 2014
  • Background: Fentanyl is used as an analgesic to treat pain in a variety of patients with cancer and recently it has become considered to also act as an antitumor agent. The study present was designed to investigate the effects of fentanyl on colorectal cancer cell growth and plausible mechanisms. Materials and Methods: The human colorectal carcinoma cell line HCT116 was subcutaneously injected into nude mice. The viability of HCT116 was tested by MTT assay, and apoptosis by flow cytometry and caspase-3 activity. The expression of Sirt1 and NF-${\kappa}B$ were evaluated by Western blotting and the levels of Sirt1 and NF-${\kappa}B$ by fluorescence method. SiRNA was used to silence and Ad-Sirt1 to overexpress Sirt1. Results: Our data showed that fentanyl could inhibit tumor growth, with increased expression of Sirt1 and down-regulation of Ac-p65 in tumors. Compared with control cells without treatment, HCT116 cells that were incubated with fentanyl had a higher apoptotic rate. Moreover, fentanyl could increase expression and activity of Sirt1 and inhibitor expression and activity of NF-${\kappa}B$, which might be mechanisms of fentanyl action. Conclusions: Fentanyl increased colorectal carcinoma cell apoptosis by inhibition of NF-${\kappa}B$ activation in a Sirt1-dependent manner.

Nano-Micelle of Moringa Oleifera Seed Oil Triggers Mitochondrial Cancer Cell Apoptosis

  • Abd-Rabou, Ahmed A;Zoheir, Khairy M A;Kishta, Mohamed S;Shalby, Aziza B;Ezzo, Mohamed I
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.11
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    • pp.4929-4934
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    • 2016
  • Cancer, a worldwide epidemic disease with diverse origins, involves abnormal cell growth with the potential to invade other parts of the body. Globally, it is the main cause of mortality and morbidity. To overcome the drawbacks of the commercially available chemotherapies, natural products-loaded nano-composites are recommended to improve cancer targetability and decrease the harmful impact on normal cells. This study aimed at exploring the anti-cancer impacts of Moringa oleifera seed oil in its free- (MO) and nano-formulations (MOn) through studying whether it mechanistically promotes mitochondrial apoptosis-mediating cell death. Mitochondrial-based cytotoxicity and flow cytometric-based apoptosis analyses were performed on cancer HepG2, MCF7, HCT 116, and Caco-2 cell lines against normal kidney BHK-21 cell line. The present study resulted that MOn triggered colorectal cancer Caco-2 and HCT 116 cytotoxicity via mitochondrial dysfunction more powerful than its free counterpart (MO). On the other side, MOn and MO remarkably induces HCT 116 mitochondrial apoptosis, while sparing normal BHK-21 cells with minimal cytotoxic effect. The present results concluded that nano-micelle of Moringa oleifera seed oil (MOn) can provide a novel therapeutic approach for colorectal and breast cancers via mitochondrial-mediated apoptosis, while sparing normal and even liver cancer cells a bit healthy or with minimal harmful effect. Intriguingly, MOn induced breast cancer not hepatocellular carcinoma cell death.

Inhibitory Effect of the Rodgersia podophylla Leave Extracts against Cell Proliferation through Activation of NF-κB in Human Colorectal Cancer Cells (도깨비부채 잎 추출물의 NF-κB 활성화를 통한 대장암 세포 HCT116에 대한 세포생육 억제활성)

  • Kim, Jeong Dong;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.33 no.5
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    • pp.460-466
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    • 2020
  • In this study, we evaluated the anti-cancer activity and potential molecular mechanism of 70% ethanol extracts of leaves from Rodgersia podophylla against human colorectal cancer cells, HCT116. RPL dose-dependently decreased the cell viability through RPL-induced apoptosis in HCT116 cells. RPL induced inactivation the nuclear factor κB(NF-κB) through blocking IκB-α degradtion and P65 nuclear accumulation. The inhibition of GSK3β by LiCl attenuated RP-L-mediated NF-κB signaling inactivation. In addition, RP-L induced GSK3β activation. Based on these findings, RPL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

NADPH oxidase inhibitor diphenyleneiodonium induces p53 expression and cell cycle arrest in several cancer cell lines (NADPH oxidase 저해제인 diphenyleneiodonium의 p53 발현 및 암세포의 성장억제에 대한 연구)

  • Jo, Hong-Jae;Kim, Kang-Mi;Song, Ju-Dong;Park, Young-Chul
    • Journal of Life Science
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    • v.17 no.6 s.86
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    • pp.778-782
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    • 2007
  • The Diphenyleneiodonium (DPI) is widely used as an inhibitor of flavoenzymes, particularly NADPH oxidase. In this study, we investigated the effect of DPI on the cell growth progression of human colon cancer cells HCT-116 (wild-type p53), HT-29 (p53 mutant) and human breast cancer cells MCF-7 (wild-type p53). DPI treatment in cancer cells evoked a dose- and time-dependent growth inhibition, and also induced the cell cycle arrest in C2/M phase. The peak of cell population arrested in C2/M phase was observed at12 hr after treatment of DPI. In addition, DPI significantly induced the expression of p53, which induces proapoptotic genes in response to DNA damage or irreparable cell cycle arrest, at 6 hr in DPI-stimulated cells. However, a catechol apocynin, which inhibits the assembly of NADPH oxidase, did not induce p53 expression. This suggest that p53 expression induced by DPI is not associated with the inhibition of NADPH oxidase. In conclusion, we suggest that DPI induces the expression of wild-type p53 by ROS-in-dependent mechanism in several cancer cells, and upregulated p53 may be involved in regulatory mechanisms for growth inhibition and cell cycle arrest at C2/M phase in DPI-stimulated cells.

Antioxidant and Anti-cancer Activities of Squash (Cucurbita moschata Duch.) Leaf Extract In vitro (호박잎 추출물의 in vitro 항산화 및 항암 효과)

  • Kwak, Youngeun;Ju, Jihyeung
    • Korean Journal of Food Science and Technology
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    • v.45 no.6
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    • pp.770-776
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    • 2013
  • The aim of this study was to investigate the antioxidant and anti-cancer activities of squash leaf extract (SLE) in vitro. The total polyphenol and flavonoid levels of SLE were 263.4 mg gallic acid equivalent/100 g and 73.6 mg quercetin equivalent/100 g, respectively. The radical-scavenging activity of SLE at the concentration of 300 ${\mu}g/mL$ was 69.4%. SLE significantly inhibited human cancer cell growth (by 60.6-87.9% in HCT116 colon cancer cells and by 73.4-86.4% in H1299 lung cancer cells at the concentrations of 37.5, 75, and 150 ${\mu}g/mL$) and attachment (by 28.4% in HCT116 and by 16.8% in H1299 at the concentration of 150 ${\mu}g/mL$). SLE also altered nucleus morphology and increased nuclear staining intensity (by 42.8-58.2% in HCT116 and by 25.5-32.9% in H1299 at the concentrations of 37.5 and 75 ${\mu}g/mL$), indicating its apoptosis-inducing activity. These results demonstrate the antioxidant and anti-cancer activities of SLE in vitro.