Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells

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Abstract

Background & Aims: Low-molecular-weight citrus pectin (LCP) is a complex polysaccharide that displays abundant galactosyl (i.e., sugar carbohydrate) residues. In this study, we evaluated the anti-tumor properties of LCP that lead to Bcl-xL -mediated dampening of apoptosis in gastrointestinal cancer cells.

Methods: We used AGS gastric cancer and SW-480 colorectal cancer cells to elucidate the effects of LCP on cell viability, cell cycle and apoptosis in cultured cells and tumor xenografts.

Results: Significantly decreased cell viabilities were observed in LCP treated AGS and SW-480 cells ( P<0.05). Cell cycle-related protein expression, such as Cyclin B1, was also decreased in LCP treated groups as compared to the untreated group. The AGS or SW-480 cell-line tumor xenografts were significantly smaller in the LCP treated group as compared the untreated group ( P<0.05). LCP treatment decreased Galectin-3 (GAL-3) expression levels, which is an important gene in cancer metastasis that results in reversion of the epithelial-mesenchymal transition (EMT), and increased suppression of Bcl-xL and Survivin to promote apoptosis. Moreover, results demonstrated synergistic tumor suppressor activity of LCP and 5-FU against gastrointestinal cancer cells both in vivo and in vitro.

Conclusions: LCP effectively inhibits the growth and metastasis of gastrointestinal cancer cells, and does so in part by down-regulating Bcl-xL and Cyclin B to promote apoptosis, and suppress EMT. Thus, LCP alone or in combination with other treatments has a high potential as a novel therapeutic strategy to improve the clinical therapy of gastrointestinal cancer.

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Galectin-3 induces endothelial cell morphogenesis and angiogenesis.

Pratima Nangia-Makker, Yuichiro Honjo, Rebecca Sarvis … (2000)

Increasing evidence suggests that carbohydrate-binding proteins play an essential role in tumor growth and metastasis. However, conflicting results on their function in the regulation of cell proliferation and differentiation during angiogenesis have been reported. We have examined the role of galectin-3 in the regulation of human umbilical vein endothelial cell proliferation, differentiation, migration, and neovascularization. Galectin-3, a carbohydrate-binding protein, with specificity for type 1 and 11 ABH blood group epitopes and polylactosamine glycan containing cell surface glycoproteins, is the major nonintegrin cellular laminin-binding protein. Because galectin-3 expression was shown to be associated in some tumor systems with metastasis, we questioned whether it induces endothelial cell morphogenesis. Here we show that galectin-3 affects chemotaxis and morphology and stimulates capillary tube formation of HUV-EC-C in vitro and angiogenesis in vivo. Endothelial cell morphogenesis is a carbohydrate-dependent process, as it is neutralized by specific sugars and antibodies. These findings demonstrate that endothelial cell surface carbohydrate recognition event(s) can induce a signaling cascade leading to the differentiation and angiogenesis of endothelial cells.

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Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer

Sahdeo Prasad, Amit K. Tyagi (2015)

Gastrointestinal (GI) cancer, a cancer of different organs of the digestive system, is one of the most common cancers around the world. The incidence and death rate of some of these cancers are very high. Although a large variety of chemotherapeutic agents have been introduced since the last few decades to combat GI cancer, most of them are very expensive and have side effects. Therefore, the compounds derived from natural sources, which are considered to be safe and cost effective, are needed. Ginger (Zingiber officinale) is one of the most widely used natural products consumed as a spice and medicine for treating nausea, dysentery, heartburn, flatulence, diarrhea, loss of appetite, infections, cough, and bronchitis. Experimental studies showed that ginger and its active components including 6-gingerol and 6-shogaol exert anticancer activities against GI cancer. The anticancer activity of ginger is attributed to its ability to modulate several signaling molecules like NF-κB, STAT3, MAPK, PI3K, ERK1/2, Akt, TNF-α, COX-2, cyclin D1, cdk, MMP-9, survivin, cIAP-1, XIAP, Bcl-2, caspases, and other cell growth regulatory proteins. In this review, the evidences for the chemopreventive and chemotherapeutic potential of ginger extract and its active components using in vitro, animal models, and patients have been described.

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Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives.

Eshvendar Reddy Kasala, Lakshmi Narendra Bodduluru, Rajaram Mohanrao Madana … (2015)

Chrysin, a naturally occurring flavone, abundantly found in numerous plant extracts including propolis and in honey is one of the most widely used herbal medicine in Asian countries. Nowadays, chrysin has become the foremost candidate exhibiting health benefits, owing to its multiple bioactivities such as antioxidant, anti-inflammatory, anti-allergic, anti-diabetic, anti-estrogenic, antibacterial and antitumor activities. Anticancer activity is most promising among the multiple pharmacological effects displayed by chrysin. In vitro and in vivo models have shown that chrysin inhibits cancer growth through induction of apoptosis, alteration of cell cycle and inhibition of angiogenesis, invasion and metastasis without causing any toxicity and undesirable side effects to normal cells. Chrysin displays these effects through selective modulation of multiple cell signaling pathways which are linked to inflammation, survival, growth, angiogenesis, invasion and metastasis of cancer cells. This broad spectrum of antitumor activity in conjunction with low toxicity underscores the translational value of chrysin in cancer therapy. The present review highlights the chemopreventive and therapeutic effects, molecular targets and antineoplastic mechanisms that contribute to the observed anticancer activity of chrysin.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Biol Sci

Journal ID (iso-abbrev): Int. J. Biol. Sci

Journal ID (publisher-id): ijbs

Title: International Journal of Biological Sciences

Publisher: Ivyspring International Publisher (Sydney )

ISSN (Electronic): 1449-2288

Publication date Collection: 2016

Publication date (Electronic): 28 April 2016

Volume: 12

Issue: 6

Pages: 746-756

Affiliations

1. Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P.R.China.

2. Department of Digestive Endoscopy, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, P.R.China.

3. Department of Pathophysiology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450052, China.

4. Institute of Food Science, Zhejiang Academy of Agriculture Science, No. 298 Desheng Rd., Hangzhou 310021, P.R.China.

Author notes

✉ Corresponding author: Zhi-Qiang Ling, M.D, Ph.D., Zhejiang Cancer Research Institute, Zhejiang Province Cancer Hospital, Zhejiang Cancer Center, No.38 Guangji Rd., Banshanqiao District, Hangzhou 310022, China. Tel: +86-571-88122423, Fax: +86-571-88122587 E-mail: lingzq@ 123456zjcc.org.cn or lingzq@ 123456hotmail.com .

Conflicts of interest: This study is not related to any potentially competing financial or other interests.

Article

Publisher ID: ijbsv12p0746

DOI: 10.7150/ijbs.13988

PMC ID: 4870717

PubMed ID: 27194951

SO-VID: 8fb82d86-558f-4244-a56f-844c3d0f07d1

Copyright © © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.

Chemoprevention of Low-Molecular-Weight Citrus Pectin (LCP) in Gastrointestinal Cancer Cells

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Most cited references 36

Galectin-3 induces endothelial cell morphogenesis and angiogenesis.

Ginger and Its Constituents: Role in Prevention and Treatment of Gastrointestinal Cancer

Chemopreventive and therapeutic potential of chrysin in cancer: mechanistic perspectives.

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