• Animal cells and systems
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• 제15권1호
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• pp.9-17
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• 2011

Colorectal cancer is the third leading cause of cancer-related death in Western countries. Chemotherapeutic agents with different mechanisms of action have shown an increase in cure rates. In the present study, we investigated the effect of a combination of low concentration of paclitaxel (taxol, 5 nM) and topoisomerase 1 inhibitor camptothecin (CPT) on HCT116 colon cancer cells. Although the viability of cells treated with taxol alone was similar to that of control cells, sequential treatment with taxol and CPT exhibited high cytotoxicity. However, the opposite sequence of treatment did not exert cytotoxic effects on HCT116 cells. This enhanced cytotoxicity of the sequential combination therapy was the result of mitotic arrest, which increased the level of $p21^{Cip1/WAF1}$ through the p38 mitogen-activated protein kinase (MAPK) pathway. Knockdown by $p21^{Cip1/WAF1}$ siRNA or treatment with a p38 inhibitor reduced the viability of cells sequentially exposed to taxol and CPT. Taken together, a low taxol concentration in combination with CPT induced mitotic arrest in HCT116 cells, leading to synergistic cell death through enhanced expression of $p21^{Cip1/WAF1}$ and p38 MAPK pathway. Therefore, taxol could playa role as a sensitizer of CPT in colon cancer cells.

• 대한한방내과학회지
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• 제31권2호
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• pp.273-289
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• 2010

Objectives : To investigate the anti-cancer effect of Baekduong-tang(BDOT) against cancer cells, the signaling pathway of apoptosis was explored in human colon cancer cells. Materials and Methods : Human colon cancer cell lines, including HT-29 and HCT-116 cells, were used. Cell viability was measured by MTT assay. Apoptosis was determined by DAPI nuclei staining and flow cytometry in HCT-116 cells treated with 0.25 mg/$m{\ell}$ Baekduong-tang for 48 hrs. Results : Baekduong-tang induced the apoptosis of p53 positive HCT-116 cells with G2/M phase arrest. Treatment with Baekduong-tang led to increased expression and phosphorylation of p53 and decreased expression of CDK2 and CDK6 in HCT-116 cells. It also activated caspase-3 through caspase-10 and caspase-9 activation. Finally, Baekduong-tang induced production $H_2O_2$, superoxide anion ($O_2^-$) and NO and modulated proteins expression including SOD, NOS, Bax and Bcl-2. Conclusions : These results indicate Baekduong-tang induces apoptotic death of HCT-116 cells through G2/M phase arrest and disturbance of intracellular redox status in a p53-dependent manner.

• Asian Pacific Journal of Cancer Prevention
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• 제15권11호
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• pp.4651-4657
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• 2014

The development of chemopreventive approaches using a concoction of phytochemicals is potentially viable for combating many types of cancer including colon carcinogenesis. This study evaluated the anti-proliferative effects of ginger and Gelam honey and its efficacy in enhancing the anti-cancer effects of 5-FU (5-fluorouracil) against a colorectal cancer cell line, HCT 116. Cell viability was measured via MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulphenyl)-2H-tetrazolium) assay showing ginger inhibiting the growth of HCT 116 cells more potently ($IC_{50}$ of 3mg/mL) in comparison to Gelam honey ($IC_{50}$ of 75mg/mL). Combined treatment of the two compounds (3mg/mL ginger+75mg/mL Gelam honey) synergistically lowered the $IC_{50}$ of Gelam honey to 22mg/mL. Combination with 35 mg/mL Gelam honey markedly enhanced 5-FU inhibiting effects on the growth of HCT 116 cells. Subsequent analysis on the induction of cellular apoptosis suggested that individual treatment of ginger and Gelam honey produced higher apoptosis than 5-FU alone. In addition, treatment with the combination of two natural compounds increased the apoptotic rate of HCT 116 cells dose-dependently while treatment of either ginger or Gelam honey combined with 5-FU only showed modest changes. Combination index analysis showed the combination effect of both natural compounds to be synergistic in their inhibitory action against HCT 116 colon cancer cells (CI 0.96 < 1). In conclusion, combined treatment of Gelam honey and ginger extract could potentially enhance the chemotherapeutic effect of 5-FU against colorectal cancer.

• 대한의생명과학회지
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• 제29권4호
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• pp.287-295
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• 2023

Amifostine was developed to protect cells, but it is known to induce cytotoxicity and apoptosis, and the exact mechanism is unknown. In this study, we investigated how the DNA mismatch repair (MMR) system interacts with p53 to prevent apoptosis, cell cycle arrest, and cytoprotective effects induced by amifostine. HCT116 colon cancer cells sublines HCT116/p53+,HCT116/p53+, HCT116/p53-, HCT116/E6 and HCT116+ch3/E6 cells were used for evaluation. Amifostine induced G1 arrest and increased toxicity two-fold in p53- cells regardless of MMR expression. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Amifostine induced the expression of p21 protein in both p53+ and p53- cells. As for apoptosis, compared to p53- cells, p53+ cells showed 3.5~4.2 times resistance to amifostine-induced apoptosis. HCT116+E6 with both p53 and MMR loss showed maximum apoptosis at 48 h, and HCT116+ch3/E6HCT116+ch3/E6 with p53 loss showed maximum apoptosis at 24 h. As a result, it was confirmed through in vitro experiments that amifostine-induced G1 cell cycle arrest and apoptosis are mediated through a pathway dependent on MMR and p53 protein.

• 생명과학회지
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• 제21권1호
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• pp.89-95
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• 2011

식품에서 추출한 파이토케미컬은 여러 암종에서 암세포의 증식억제와 apoptosis를 유도한다. 최근에 이러한 파이토케미컬의 세포 내 신호전달 기작에 관한 관심이 높아지고 있으며, 본 연구에서는 파이토케미컬의 일종인 커큐민과 EGCG를 HCT116 대장암세포에 처리함으로써 암세포의 증식억제와 apoptosis 유도 효과를 알아보고, 암세포의 증식에 관여하는 Akt의 활성과 종양 억제유전자인 p53의 신호경로를 규명하고자 하였다. 그 결과, 커큐민과 EGCG를 처리했을 때 HCT116 세포의 증식이 억제되었고, 암세포에서 apoptosis 효과가 나타남을 확인하였다. 동일한 조건에서 Western blotting을 실시했을 때 Akt의 활성은 감소하였으며 p53의 발현은 증가하였다. 또한 Akt의 저해제인 LY294002를 처리했을 때 암세포의 증식이 더욱 강하게 억제되었으며, p53의 발현은 더욱 강하게 증가하는 것으로 나타났다. 따라서 HCT116 세포에서 커큐민과 EGCG 처리에 의한 암세포의 증식 억제 및 apoptosis는 p53의 발현이 증가함에 따라 유도되며, 이러한 p53의 발현 증가는 Akt 신호경로를 저해함으로써 일어난다는 것을 확인하였다.

• Natural Product Sciences
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• 제22권3호
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• pp.209-215
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• 2016

Kigelia africana (Lam.) Benth. (Bignoniaceae) is a flowering plants in South, Central and West Africa and commonly known as the sausage tree (Eng.); worsboom (Afr.); umVunguta, umFongothi (Zulu); Modukguhlu (North Sotho); Muvevha (Venda). The dried, powdered fruits are used as dressing for wounds and ulcers, haemorrhoids, rheumatism, purgative, skin-firming, lactation in breast-feeding mothers. The aim of this study is to investigate the cytotoxic and apoptotic potentials of 70% ethanolic extracts of Kigelia africana fruits in HCT116 human colon cancer cells. Treatment of Kigelia africana fruits with various concentrations resulted in a sequence of characteristic of apoptosis, including loss of cell viability and morphological changes. Flow cytometry analysis showed Kigelia africana fruits increased the sub-G1 phase (apoptosis) population. Apoptosis confirmed by annexin V-fluorescein isothiocyanate and propidium iodide double staining in HCT116 human colon cancer cell lines. Moreover, analysis of the mechanism indicated that Kigelia africana fruits showed an increased Bax and Bcl-2 expressions in a dose-dependent manner, resulting in activation of hallmarks of apoptotic events, caspase-3, caspase-9 and cleaved poly-ADP-ribose polymerase. This is the first report to demonstrate the cytotoxicity of Kigelia africana fruits on HCT116 human colon cancer cells.

• International Journal of Oral Biology
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• 제46권1호
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• pp.7-14
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• 2021

Vinpocetine induces anti-inflammatory effects in various inflammatory diseases via the inhibition of phosphodiesterase type-1-independent nuclear factor-κB signaling pathway and the release of inflammatory cytokines. In this study, we investigated the effect of vinpocetine on the proliferation of colon cancer cells and its underlying molecular mechanisms. Our data showed that vinpocetine inhibits the viability and proliferation of colon cancer cells. Vinpocetine treatment induced cell death in HCT116 cells, which the percentages of sub-G1 phase were significantly increased, and the apoptosis-related genes were regulated after HCT116 cells were treated with vinpocetine. In sum, our findings indicated that vinpocetine could be a therapeutically useful candidate in the treatment of colon cancer.

• Nutrition Research and Practice
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• 제8권5호
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• pp.487-493
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• 2014

BACKGROUND/OBJECTIVES: D. candidum is a traditional Chinese food or medicine widely used in Asia. There has been little research into the anticancer effects of D. candidum, particularly the effects in colon cancer cells. The aim of this study was to investigate the anticancer effects of D. candidum in vitro and in vivo. MATERIALS/METHODS: The in vitro anti-cancer effects on HCT-116 colon cancer cells and in vivo anti-metastatic effects of DCME (Dendrobium canidum methanolic extract) were examined using the experimental methods of MTT assay, DAPI staining, flow cytometry analysis, RT-PCR, and Western blot analysis. RESULTS: At a concentration of 1.0 mg/mL, DCME inhibited the growth of HCT-116 cells by 84%, which was higher than at concentrations of 0.5 and 0.25 mg/mL. Chromatin condensation and formation of apoptotic bodies were observed in cancer cells cultured with DCME as well. In addition, DCME induced significant apoptosis in cancer cells by upregulation of Bax, caspase 9, and caspase 3, and downregulation of Bcl-2. Expression of genes commonly associated with inflammation, NF-${\kappa}B$, iNOS, and COX-2, was significantly downregulated by DCME. DCME also exerted an anti-metastasis effect on cancer cells as demonstrated by decreased expression of MMP genes and increased expression of TIMPs, which was confirmed by the inhibition of induced tumor metastasis in colon 26-M3.1 cells in BALB/c mice. CONCLUSIONS: Our results demonstrated that D. candidum had a potent in vitro anti-cancer effect, induced apoptosis, exhibited anti-inflammatory activities, and exerted in vivo anti-metastatic effects.

• The Korean Journal of Physiology and Pharmacology
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• 제21권2호
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• pp.267-273
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• 2017

The p53-inducible gene 3 (PIG3), initially identified as a gene downstream of p53, plays an important role in the apoptotic process triggered by p53-mediated reactive oxygen species (ROS) production. Recently, several studies have suggested that PIG3 may play a role in various types of cancer. However, the functional significance of PIG3 in cancer remains unclear. Here, we found that PIG3 was highly expressed in human colon cancer cell lines compared to normal colon-derived fibroblasts. Therefore, we attempted to elucidate the functional role of PIG3 in colon cancer. PIG3 overexpression increases the colony formation, migration and invasion ability of HCT116 colon cancer cells. Conversely, these tumorigenic abilities were significantly decreased in in vitro studies with PIG3 knockdown HCT116 cells. PIG3 knockdown also attenuated the growth of mouse xenograft tumors. These results demonstrate that PIG3 is associated with the tumorigenic potential of cancer cells, both in vitro and in vivo, and could play a key oncogenic role in colon cancer.

• Asian Pacific Journal of Cancer Prevention
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• 제15권13호
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• pp.5201-5205
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• 2014

Emodin, a natural anthraquinone isolated from the traditional Chinese medicine Radix rhizoma Rhei, can induce apoptosis in many kinds of cancer cells. This study demonstrated that emodin induces apoptosis in human colon cancer HCT116 cells by provoking oxidative stress, which subsequently triggers a p53-mitochondrial apoptotic pathway. Emodin induced mitochondrial transmembrane potential loss, increase in Bax and decrease in Bcl-2 expression and mitochondrial translocation and release of cytochrome c to cytosol in HCT116 cells. In response to emodin-treatment, ROS increased rapidly, and subsequently p53 was overexpressed. Pretreatment with the antioxidant NAC diminished apoptosis and p53 overexpression induced by emodin. Transfecting p53 siRNA also attenuated apoptosis induced by emodin, Bax expression and mitochondrial translocation being reduced compared to treatment with emodin alone. Taken together, these results indicate that ROS is a trigger of emodin-induced apoptosis in HCT116 cells, and p53 expression increases under oxidative stress, leading to Bax-mediated mitochondrial apoptosis.