Fucoxanthin and Colorectal Cancer Prevention

Colorectal cancer (CRC), which ranks among the top 10 most prevalent cancers, can obtain a good outcome with appropriate surgery and/or chemotherapy. However, the global numbers of both new cancer cases and death from CRC are expected to increase up to 2030. Diet-induced lifestyle modification is suggested to be effective in reducing the risk of human CRC; therefore, interventional studies using diets or diet-derived compounds have been conducted to explore the prevention of CRC. Fucoxanthin (Fx), a dietary carotenoid, is predominantly contained in edible brown algae, such as Undaria pinnatifida (wakame) and Himanthalia elongata (Sea spaghetti), which are consumed particularly frequently in Asian countries but also in some Western countries. Fx is responsible for a majority of the anticancer effects exerted by the lipophilic bioactive compounds in those algae. Interventional human trials have shown that Fx and brown algae mitigate certain risk factors for CRC; however, the direct mechanisms underlying the anti-CRC properties of Fx remain elusive. Fx and its deacetylated type “fucoxanthinol” (FxOH) have been reported to exert potential anticancer effects in preclinical cancer models through the suppression of many cancer-related signal pathways and the tumor microenvironment or alteration of the gut microbiota. We herein review the most recent studies on Fx as a potential candidate drug for CRC prevention.

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Anticancer effects against colorectal cancer models of chloro(triethylphosphine)gold(I) encapsulated in PLGA–PEG nanoparticles

BioMetals ◽

10.1007/s10534-021-00313-0 ◽

2021 ◽

Author(s):

Alessio Menconi ◽

Tiziano Marzo ◽

Lara Massai ◽

Alessandro Pratesi ◽

Mirko Severi ◽

...

Keyword(s):

Colorectal Cancer ◽

Gold Complex ◽

Drug Candidate ◽

Side Reactions ◽

Anticancer Effects ◽

Cancer Models ◽

Free Gold ◽

Hct 116 ◽

New Formulation

AbstractChloro(triethylphosphine)gold(I), (Et3PAuCl hereafter), is an Auranofin (AF)-related compound showing very similar biological and pharmacological properties. Like AF, Et3PAuCl exhibits potent antiproliferative properties in vitro toward a variety of cancer cell lines and is a promising anticancer drug candidate. We wondered whether Et3PAuCl encapsulation might lead to an improved pharmacological profile also considering the likely reduction of unwanted side-reactions that are responsible for adverse effects and for drug inactivation. Et3PAuCl was encapsulated in biocompatible PLGA–PEG nanoparticles (NPs) and the new formulation evaluated in colorectal HCT-116 cancer cells in comparison to the free gold complex. Notably, encapsulated Et3PAuCl (nano-Et3PAuCl hereafter) mostly retains the cellular properties of the free gold complex and elicits even greater cytotoxic effects in colorectal cancer (CRC) cells, mediated by apoptosis and autophagy. Moreover, a remarkable inhibition of two crucial signaling pathways, i.e. ERK and AKT, by nano-Et3PAuCl, was clearly documented. The implications of these findings are discussed.

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Resveratrol and Its Nanoformulation Attenuate Growth and the Angiogenesis of Xenograft and Orthotopic Colon Cancer Models

Molecules ◽

10.3390/molecules25061412 ◽

2020 ◽

Vol 25 (6) ◽

pp. 1412 ◽

Cited By ~ 3

Author(s):

Thangirala Sudha ◽

Ali H. El-Far ◽

Deena S. Mousa ◽

Shaker A. Mousa

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Natural Compound ◽

Anticancer Effect ◽

Tumor Mass ◽

The Third ◽

Common Cancer ◽

Cancer Models ◽

Prevention And Treatment ◽

Colorectal Cancer Prevention

Cancer is a multifactorial disorder that induces mortality worldwide, and the colorectal type is the third most common cancer globally. Resveratrol (RSV) is a natural compound with an effective anticancer effect, especially against colorectal cancer, and therefore numerous studies recommended its use in colorectal cancer prevention and treatment. The current study investigated the effect of either RSV or its nanoformulation (NP-RSV) on the growth and vascularity of xenograft and orthotopic mice models in colon cancer (COLO205-luc). Both RSV and NP-RSV induced significant reductions in tumor growth and the hemoglobin percentages of the tumor mass, but NP-RSV showed greater bioavailability and efficacy than RSV. Generally, we recommend using NP-RSV as a therapeutic to control colon cancer.

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Phytosomal Curcumin Elicits Anti-tumor Properties Through Suppression of Angiogenesis, Cell Proliferation and Induction of Oxidative Stress in Colorectal Cancer

Current Pharmaceutical Design ◽

10.2174/1381612825666190110145151 ◽

2019 ◽

Vol 24 (39) ◽

pp. 4626-4638 ◽

Cited By ~ 13

Author(s):

Reyhaneh Moradi-Marjaneh ◽

Seyed M. Hassanian ◽

Farzad Rahmani ◽

Seyed H. Aghaee-Bakhtiari ◽

Amir Avan ◽

...

Keyword(s):

Oxidative Stress ◽

Colorectal Cancer ◽

Therapeutic Potential ◽

Vegf Signaling ◽

Anticancer Effects ◽

Inhibition Of Angiogenesis ◽

Underlying Mechanisms ◽

Apoptotic Activity

Background: Colorectal cancer (CRC) is one of the most common causes of cancer-associated mortality in the world. Anti-tumor effect of curcumin has been shown in different cancers; however, the therapeutic potential of novel phytosomal curcumin, as well as the underlying molecular mechanism in CRC, has not yet been explored. Methods: The anti-proliferative, anti-migratory and apoptotic activity of phytosomal curcumin in CT26 cells was assessed by MTT assay, wound healing assay and Flow cytometry, respectively. Phytosomal curcumin was also tested for its in-vivo activity in a xenograft mouse model of CRC. In addition, oxidant/antioxidant activity was examined by DCFH-DA assay in vitro, measurement of malondialdehyde (MDA), Thiol and superoxidedismutase (SOD) and catalase (CAT) activity and also evaluation of expression levels of Nrf2 and GCLM by qRT-PCR in tumor tissues. In addition, the effect of phytosomal curcumin on angiogenesis was assessed by the measurement of VEGF-A and VEGFR-1 and VEGF signaling regulatory microRNAs (miRNAs) in tumor tissue. Results: Phytosomal curcumin exerts anti-proliferative, anti-migratory and apoptotic activity in-vitro. It also decreases tumor growth and augmented 5-fluorouracil (5-FU) anti-tumor effect in-vivo. In addition, our data showed that induction of oxidative stress and inhibition of angiogenesis through modulation of VEGF signaling regulatory miRNAs might be underlying mechanisms by which phytosomal curcumin exerted its antitumor effect. Conclusion: Our data confirmed this notion that phytosomal curcumin administrates anticancer effects and can be used as a complementary treatment in clinical settings.

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Hemistepsin A suppresses colorectal cancer growth through inhibiting pyruvate dehydrogenase kinase activity

Scientific Reports ◽

10.1038/s41598-020-79019-1 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ling Jin ◽

Eun-Yeong Kim ◽

Tae-Wook Chung ◽

Chang Woo Han ◽

So Young Park ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Pyruvate Dehydrogenase ◽

Cancer Metabolism ◽

Aerobic Glycolysis ◽

Lactate Production ◽

Pyruvate Dehydrogenase Kinase ◽

Cancer Drug ◽

Potential Candidate ◽

Mitochondrial Ros

AbstractMost cancer cells primarily produce their energy through a high rate of glycolysis followed by lactic acid fermentation even in the presence of abundant oxygen. Pyruvate dehydrogenase kinase (PDK) 1, an enzyme responsible for aerobic glycolysis via phosphorylating and inactivating pyruvate dehydrogenase (PDH) complex, is commonly overexpressed in tumors and recognized as a therapeutic target in colorectal cancer. Hemistepsin A (HsA) is a sesquiterpene lactone isolated from Hemistepta lyrata Bunge (Compositae). Here, we report that HsA is a PDK1 inhibitor can reduce the growth of colorectal cancer and consequent activation of mitochondrial ROS-dependent apoptotic pathway both in vivo and in vitro. Computational simulation and biochemical assays showed that HsA directly binds to the lipoamide-binding site of PDK1, and subsequently inhibits the interaction of PDK1 with the E2 subunit of PDH complex. As a result of PDK1 inhibition, lactate production was decreased, but oxygen consumption was increased. Mitochondrial ROS levels and mitochondrial damage were also increased. Consistent with these observations, the apoptosis of colorectal cancer cells was promoted by HsA with enhanced activation of caspase-3 and -9. These results suggested that HsA might be a potential candidate for developing a novel anti-cancer drug through suppressing cancer metabolism.

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Prediction of 10-year and lifetime risk of cancer in individual patients with established cardiovascular disease, results from UCC-SMART and CANTOS

European Heart Journal ◽

10.1093/ehjci/ehaa946.2815 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

C.C Van 't Klooster ◽

P.M Ridker ◽

N.R Cook ◽

J.G.J.V Aerts ◽

J Westerink ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Factors ◽

Lung Cancer ◽

Cancer Risk ◽

Prediction Models ◽

Funding Source ◽

Cancer Models ◽

Total Cancer ◽

The Cantos ◽

Risk Of Cancer

Abstract Background As treatment for cardiovascular disease (CVD) has improved substantially over the last decades, more patients survive acute CVD manifestations and are at risk for developing cancer as well as recurrent CVD. Due to similar risk factors, including smoking and obesity, patients with established CVD are at higher risk for cancer. Objectives The aim of this study was to develop and externally validate prediction models for the estimation of 10-year and lifetime risk for total, colorectal, and lung cancer in patients with established CVD. Methods Data from patients with established CVD from the UCC-SMART prospective cohort study (N=7,280) were used for model development, and data from the CANTOS trial (N=9,322) were used for model validation. Predictors were selected based on previously published cancer risk prediction models or cancer risk factors, easy clinical availability, and availability in the derivation dataset (UCC-SMART cohort). A Fine and Gray competing risk-adjusted lifetime model was developed for total, colorectal, and lung cancer. Results Selected predictors were age, sex, smoking status, weight, height, alcohol use, antiplatelet use, diabetes mellitus, and C-reactive protein. External calibration for 4-year risks of the total cancer, colorectal cancer, and lung cancer models was good (Figure 1), and C-statistics were 0.63–0.74 in the CANTOS trial population. Median predicted lifetime risks in CANTOS were 26% (range 1%-52%) for total cancer, 4% (range 0%-13%) for colorectal cancer, and 5% (range 0%-37%) for lung cancer. Conclusions Lifetime and 10-year risk of cancer can be estimated with easy to measure variables in patients with established CVD, showing a wide distribution of predicted lifetime risks for total cancer and lung cancer. Using these lifetime models in clinical practice could increase understanding of cancer risk and aid in emphasizing healthy lifestyle changes. Figure 1. Calibration plots of cancer models Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): University Medical Center; Additional funding: CANTOS trial was funded by Novartis Pharmaceuticals.

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Anticancer effects of bifidobacteria on colon cancer cell lines

Cancer Cell International ◽

10.1186/s12935-021-01971-3 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zeinab Faghfoori ◽

Mohammad Hasan Faghfoori ◽

Amir Saber ◽

Azimeh Izadi ◽

Ahmad Yari Khosroushahi

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cancer Cells ◽

Cell Lines ◽

Cancer Cell ◽

Colon Cancer Cell ◽

Rt Pcr ◽

Anticancer Effects ◽

Colon Cancer Cell Lines ◽

Apoptotic Genes

Abstract Background Colorectal cancer (CRC), with a growing incidence trend worldwide, is resistant to apoptosis and has uncontrolled proliferation. It is recently reported that probiotic microorganisms exert anticancer effects. The genus Bifidobacterium, one of the dominant bacterial populations in the gastrointestinal tract, has received increasing attention because of widespread interest in using it as health-promoting microorganisms. Therefore, the present study aimed to assess the apoptotic effects of some bifidobacteria species on colon cancer cell lines. Methods The cytotoxicity evaluations performed using MTT assay and FACS-flow cytometry tests. Also, the effects of five species of bifidobacteria secretion metabolites on the expression level of anti- or pro-apoptotic genes including BAD, Bcl-2, Caspase-3, Caspase-8, Caspase-9, and Fas-R studied by real-time polymerase chain reaction (RT-PCR) method. Results The cell-free supernatant of all studied bifidobacteria significantly decreased the survival rates of colon cancer cells compared with control groups. Flow cytometric and RT-PCR results indicated that apoptosis is induced by bifidobacteria secretion metabolites and the mechanism for the action of bifidobacteria species in CRC prevention could be down-regulation and up-regulation of anti-apoptotic and, pro-apoptotic genes. Conclusions In the present study, different bifidobacteria species showed anticancer activity on colorectal cancer cells through down-regulation and up-regulation of anti-apoptotic and pro-apoptotic genes. However, further studies are required to clarify the exact mechanism of apoptosis induction by bifidobacteria species.

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Extract of Pogostemon cablin Possesses Potent Anticancer Activity against Colorectal Cancer Cells In Vitro and In Vivo

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/9758156 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Ju-Huei Chien ◽

Shan-Chih Lee ◽

Kai-Fu Chang ◽

Xiao-Fan Huang ◽

Yi-Ting Chen ◽

...

Keyword(s):

Colorectal Cancer ◽

Cell Apoptosis ◽

Cycle Arrest ◽

Anticancer Effects ◽

Pogostemon Cablin ◽

Colorectal Cancer Cells ◽

Potential Applicability ◽

Cancer Suppression

Pogostemon cablin (PCa), an herb used in traditional Chinese medicine, is routinely used in the amelioration of different types of gastrointestinal discomfort. However, the mechanisms underlying the cancer suppression activity of PCa in colorectal cancer (CRC) cells have yet to be clarified. The aim of this study was to investigate the anticancer effects of PCa, specifically the induction of apoptosis in CRC cells. The growth inhibition curve of CRC cells following exposure to PCa was detected by an MTT assay. Moreover, PCa combined with 5-FU revealed a synergic effect of decreased cell viability. PCa inhibited cell proliferation and induced cell cycle arrest at the G0/G1 phase and cell apoptosis through regulation of associated protein expression. An in vivo study showed that PCa suppressed the growth of CRC via induction of cell apoptosis with no significant change in body weight or organ histology. Our results demonstrated that PCa inhibits the growth of CRC cells and induces apoptosis in vitro and in vivo, which suggests the potential applicability of PCa as an anticancer agent.

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