• Nutrition Research and Practice
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• 제18권1호
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• pp.62-77
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• 2024

BACKGROUND/OBJECTIVES: Colorectal cancer (CRC) is the third most common cancer worldwide with a high recurrence rate. Oxaliplatin (OXA) resistance is one of the major reasons hindering CRC therapy. β-Carotene (BC) is a provitamin A and is known to have antioxidant and anticancer effects. However, the combined effect of OXA and BC has not been investigated. Therefore, this study investigated the anticancer effects and mechanism of the combination of OXA and BC on CRC. MATERIALS/METHODS: In the present study, the effects of the combination of OXA and BC on cell viability, cell cycle arrest, and cancer stemness were investigated using HCT116, HT29, OXA-resistant cells, and human CRC organoids. RESULTS: The combination of OXA and BC enhanced apoptosis, G₂/M phase cell cycle arrest, and inhibited cancer cell survival in human CRC resistant cells and CRC organoids without toxicity in normal organoids. Cancer stem cell marker expression and self-replicating capacity were suppressed by combined treatment with OXA and BC. Moreover, this combined treatment upregulated apoptosis and the stem cell-related JAK/STAT signaling pathway. CONCLUSIONS: Our results suggest a novel potential role of BC in reducing resistance to OXA, thereby enhances the anticancer effects of OXA. This enhancement is achieved through the regulation of cell cycle, apoptosis, and stemness in CRC.

• 한국자원식물학회지
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• 제29권3호
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• pp.297-304
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• 2016

The seed of safflower (Carthamus tinctorius L) has been reported to suppress human cancer cell proliferation. However, the mechanisms by which safflower seed inhibits cancer cell proliferation have remained nuclear. In this study, the inhibitory effect of the safflower seed (SS) on the proliferation of human colorectal cancer cells and the potential mechanism of action were examined. SS inhibited markedly the proliferation of human colorectal cancer cells (HCT116, SW480, LoVo and HT-29). In addition, SS suppressed the proliferation of human breast cancer cells (MDA-MB-231 and MCF-7). SS treatment decreased cyclin D1 protein level in human colorectal cancer cells and breast cancer cells. But, SS-mediated downregulated mRNA level of cyclin D1 was not observed. Inhibition of proteasomal degradation by MG132 attenuated cyclin D1 downregulation by SS and the half-life of cyclin D1 was decreased in SS-treated cells. In addition, SS increased cyclin D1 phosphorylation at threonine-286 and a point mutation of threonine-286 to alanine attenuated SS-mediated cyclin D1 degradation. Inhibition of ERK1/2 by PD98059 suppressed cyclin D1 phosphorylation and downregulation of cyclin D1 by SS. In conclusion, SS has anti-proliferative activity by inducing cyclin D1 proteasomal degradation through ERK1/2-dependent threonine-286 phosphorylation of cyclin D1. These findings suggest that possibly its extract could be used for treating colorectal cancer.

• Bulletin of the Korean Chemical Society
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• 제29권7호
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• pp.1303-1310
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• 2008

Inhibitors of farnesyltransferase (FT), a key enzyme in the post-translational modifications of Ras proteins, have been extensively studied as novel anticancer agents in the preclinical stages, some of which are currently in clinical development. Previously, it has been reported that a novel FT inhibitor LB42907 inhibits Ras farnesylation in the nanomolar range in vitro. The aim of this study was to assess the antitumor efficacy of LB42907 in vitro and in vivo. Anchorage-independent growth of various human tumor cell lines was potently inhibited by treatment with LB42907, comparable to other FT inhibitors in clinical development. In the nude mouse, oral administration of LB42907 demonstrated potent antitumor activity in several human tumor xenograft models including bladder, lung and pancreas origin. Interestingly, significant tumor regression in EJ (bladder) and A549 (lung) xenografts was induced by LB42907 treatment. The effectiveness of LB42907 was also investigated in simultaneous combination with paclitaxel, vincristine, cisplatin or gemcitabine against NCI-H460, A549, and HCT116 cells in vitro using median-effect analysis. LB42907 markedly synergized with most anticancer drugs tested in this study in NCI-H460 cell. In contrast, LB42907 displayed antagonism or partial synergism with these drugs in A549 and HCT116 cells, depending on the class of combined drugs and/ or the level of cytotoxicity. Our results demonstrate that LB42907 is an effective antitumor agent in vitro and in vivo and combination of LB42907 with other chemotherapeutic drugs results in synergistic or antagonistic effects mainly in a cell line-dependent manner. Further preclinical study is warranted.

• 생명과학회지
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• 제21권2호
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• pp.194-201
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• 2011

Caudal homeodomain 단백질은 초파리에서 사람에 이르기까지 보존되어 있으며, 장조직의 발생과 유지에 필수적인 역할을 한다. CDX1과 CDX2의 발현 감소 혹은 소실이 대장암과 연관되어 있음이 잘 알려져 있다. 대장암 발생은 산화성 스트레스와 밀접한 관련이 있으며, 대장암 조직에서 항산화효소인 catalase의 발현이 감소되어 있다. 하지만 그 분자적 기전은 잘 밝혀져 있지 않다. 본 연구에서는 초파리와 사람의 caudal homeodomain 단백질들이 catalase의 발현을 조절하는 것을 보여준다. 초파리 caudal heterozygous 돌연변이체의 대장조직에서 catalase의 발현이 감소되어 있고 ROS 생성이 증가되어 있음을 관찰하였다. 그리고 caudal 유전자의 과발현에 의해 catalase promoter의 활성과 mRNA 수준이 각각 증가함을 확인하였다. 또한 사람의 대장암 세포주인 HCT116 세포에서 CDX1과 CDX2가 catalase promoter의 활성과 단백질 수준에서 catalase를 상향 조절함을 관찰하였다. 이러한 결과들은 CDX1과 CDX2가 catalase 발현 조절을 통하여 장의 항상성 유지와 암발생 과정에 관여함을 시사한다.

• Nutrition Research and Practice
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• 제6권5호
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• pp.396-404
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• 2012

The aim of the study was to investigate the inhibitory effects of calcium against intestinal cancer in vitro and in vivo. We first investigated the effects of calcium treatment in HCT116 and HT29 human colon cancer cells. At the concentration range of 0.8-2.4 mM, calcium significantly inhibited cell growth (by 9-29%), attachment (by 12-26%), invasion (by 15-31%), and migration (by 19-61%). An immunofluorescence microscope analysis showed that the treatment with calcium (1.6 mM) for 24 h increased plasma membrane ${\beta}$-catenin but decreased nuclear ${\beta}$-catenin levels in HT29 cells. We then investigated the effect of dietary calcium on intestinal tumorigenesis in $Apc^{Min/+}$ mice. Mice received dietary treatment starting at 6 weeks of age for the consecutive 8 weeks. The basal control diet contained high-fat (20% mixed lipids by weight) and low-calcium (1.4 mg/g diet) to mimic the average Western diet, while the treatment diet contained an enriched level of calcium (5.2 mg calcium/g diet). The dietary calcium treatment decreased the total number of small intestinal tumors (by 31.4%; P < 0.05). The largest decrease was in tumors which were ${\geq}$ 2 mm in diameter, showing a 75.6% inhibition in the small intestinal tumor multiplicity (P < 0.001). Immunohistochemical analysis showed significantly reduced nuclear staining of ${\beta}$-catenin (expressed as nuclear positivity), but increased plasma membrane staining of ${\beta}$-catenin, in the adenomas from the calcium-treated groups in comparison to those from the control group (P < 0.001). These results demonstrate intestinal cancer inhibitory effects of calcium both in human colon cancer cells and $Apc^{Min/+}$ mice. The decreased ${\beta}$-catenin nuclear localization caused by the calcium treatment may contribute to the inhibitory action.

• 생명과학회지
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• 제22권1호
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• pp.41-48
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• 2012

봉독은 동양의학에서 관절염, 류마티즘 및 각종 암을 포함하여 다양한 질병을 치료하기 위하여 이용되었다. 최근 봉독의 신생혈관 억제효과에 대한 연구가 보고되었으나 정확한 분자메커니즘에 대해서는 보고가 미흡하다. 따라서, 본 연구는 봉독이 인간결장암세포인 HCT116세포에서 신생혈관생성과 종양진행에 중요한 역할을 하는 HIF-$1{\alpha}$와 VEGF 발현 억제효과를 조사하였다. 그 결과 봉독은 $CoCl_2$로 유도한 저산소 상태에서 VEGF와, HIF-$1{\alpha}$의 발현을 감소시키며 HIF-$1{\alpha}$의 promoter 영역인 HRE 활성을 억제하였다. 이러한 봉독의 HIF-$1{\alpha}$ 발현억제효과는 ERK1/2의 인산화 조절을 통한 것이며, 봉독은 p38, JNK, AKT의 인산화에는 영향을 끼치지 않았다. 또한 봉독의 효과를 나타내는 단일물질 탐색을 위해 봉독의 생리활성 물질로 알려진 아파민과 멜리틴을 조사한 결과, HIF-$1{\alpha}$와 VEGF 억제효과는 아파민에 기인하는 것이라고 예상 할 수 있었다. 이와 같은 결과를 통하여 본 연구에서는 봉독의 혈관신생 억제에 대한 새로운 신호전달기전 및 인간 결장암세포 전이 억제제로서의 잠재성을 확인하였다.

• 한국식품영양과학회지
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• 제45권6호
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• pp.918-922
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• 2016

본 연구에서는 귀리 추출물에 대한 항산화 활성과 암세포 증식 억제 활성을 측정하고 각 추출용매에 따른 차이를 비교 분석하고자 하였다. 추출물의 항산화 활성은 2,2-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)와 1,1-diphenyl-2-picrylhydrazyl(DPPH) 라디칼 제거능 및 환원력을 이용하여 측정하였으며, 암세포 증식 억제 활성은 대장암, 폐암 및 유방암 세포주를 이용하여 평가하였다. 총 폴리페놀 함량, ABTS 및 DPPH 라디칼 제거능, 환원력 모두 methanol 추출물이 각각 8.2 mg gallic acid equivalent/g residue, 12.1 mg Trolox equivalent antioxidant capacity(TEAC)/g residue, 4.4 mg TEAC/g residue 및 $A_{700}=0.39$로 가장 높은 활성을 나타내었다. 또한 암세포 증식 억제 활성은 methanol 추출물이 대장암(HCT116), 폐암(NCI-H460) 및 유방암(MCF7) 세포에서 각각 69.5, 75.2 및 84.8%로 높은 증식 억제 활성을 나타내었다. 따라서 추출용매에 따라 귀리의 항산화 및 암세포 증식 억제 활성에 차이가 나타나며, 이는 추출용매의 극성에 따라 추출된 생리활성 물질, 특히 폴리페놀 화합물의 용해도 차이로 생각된다. 본 연구 결과는 점차 관심이 높아지고 있는 천연 항산화제 및 항암제로서 귀리에 관한 생리활성 연구에 있어 기초자료로 활용될 수 있을 것으로 생각되며, 귀리의 소비 촉진에 영향을 끼칠 것으로 생각된다.

• 한국식품영양과학회지
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• 제41권7호
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• pp.881-887
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• 2012

유산균과 금은화, 발효 금은화는 장누수 증후군과 연관된 장 상피세포 점막 투과성 감소에 대하여 유의한 효과를 나타내었다. 따라서 유산균을 단독으로 사용하는 방법과 유산균을 이용해 발효시킨 금은화를 증가된 장 투과성 및 장내미생물 불균형으로 인한 장누수 증후군과 관련된 일련의 증상들을 치료하고 면역관련 질환 및 만성 염증성 질환에도 응용할 수 있을 것으로 예상되며 이에 대한 앞으로의 추가 연구가 필요할 것으로 사료된다.

• Journal of Applied Biological Chemistry
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• 제63권1호
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• pp.103-110
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• 2020

Objective: The objective of our study was to investigate anti-cancer effects of Danggui Liuhuang Decoction extract bioconverted by protease liquid coenzyme of Aspergillus kawachii (DLD-BE), compared to a non-bioconverted DLD extract (DLD-E) and determine the underlying mechanisms. Methods: DLD-E and DLD-BE were evaluated for their ability to modulate these signaling pathways and suppress the proliferation of human colorectal cancer (CRC) cells, HCT-116, LoVo, and HT-29. The anti-cancer effects of DLD-E and DLD-BE were measured by using proliferation and migration assays, cell cycle analysis, Western blots, and real-time PCR. Results: In this study, treatment with DLD-E and DLD-BE at concentrations of 25-100 ㎍/mL inhibited proliferation and migration in human CRC cells. DLD-BE induced apoptotic cell death and decreased COX-2 expression in HT-29 cells. The mechanisms of action included modulation of the AKT and extracellular-signal-regulated kinase signaling cascades along with inhibition of COX-2 expression. The results demonstrate novel anti-cancer mechanisms of DLD-BE against the growth of human CRC cells. Thus, we propose that DLD-BE can be developed as a more potent supplement to inhibit colorectal tumor growth and intestinal inflammation than DLD-E.

• Journal of Microbiology and Biotechnology
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• 제21권6호
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• pp.582-589
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• 2011

Bioconversion of timosaponin A-III (TA-III), one of the major steroidal saponins isolated from the rhizomes of Anemarrhenae asphodeloides Bunge (Liliaceae), was investigated in Saccharomyces cerevisiae. Five bioconversion products, denoted compounds 2-6, were obtained. Biotransformation metabolite 2 was a stereoisomer of TAIII with a specific isotype F-ring and ${\beta}$-ranged $CH_3$-21, which rarely occurs in nature. The structure of 2 was elucidated by extensive spectroscopic analysis (H-H COSY, HSQC, HMBC), as well as by high-resolution mass spectral analysis. The growth inhibitory activity of compounds 1-6 was assayed against four human cancer cell lines, HepG2, H-1299, HT-29, and HCT-116. Compounds 1 and 2 obviously inhibited the growth of the four types of cancer cells with $IC_{50}$ values being less than 19${\mu}M$. A structure-activity relationship is discussed, and the spirostane-ring F in compounds 1 and 2 appears to be the critical bioactive moiety for the cell growth inhibitory property.