Inhibition of DMH‑DSS‑induced colorectal cancer by liposomal bovine lactoferrin in rats

Sugihara, Yoshikazu; Zuo, Xiaoxu; Takata, Takashi; Jin, Shengjian; Miyauti, Mutumi; Isikado, Atusi; Imanaka, Hiromichi; Tatsuka, Masaaki; Qi, Guangying; Shimamoto, Fumio

doi:10.3892/ol.2017.6976

Cited by 22 publications

(20 citation statements)

References 36 publications

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“…Generally, hLf and bLf have been shown to exert anti-cancer activity for both tumor prevention and treatment [18,109]. The Lf preventive effect has been demonstrated in several animal models bearing different types of tumors, including lung, tongue, esophagus, liver, and colorectal [110][111][112][113], whereas Lf treatment was found efficient in inhibiting growth, metastasis, and tumor-associated angiogenesis [18,114,115], as well as in boosting chemotherapy [116,117].…”

Section: Lactoferrin and Cancermentioning

confidence: 99%

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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Despite recent advances in cancer therapy, current treatments, including radiotherapy, chemotherapy, and immunotherapy, although beneficial, present attendant side effects and long-term sequelae, usually more or less affecting quality of life of the patients. Indeed, except for most of the immunotherapeutic agents, the complete lack of selectivity between normal and cancer cells for radioand chemotherapy can make them potential antagonists of the host anti-cancer self-defense over time. Recently, the use of nutraceuticals as natural compounds corroborating anti-cancer standard therapy is emerging as a promising tool for their relative abundance, bioavailability, safety, low-cost effectiveness, and immuno-compatibility with the host. In this review, we outlined the anti-cancer properties of Lactoferrin (Lf), an iron-binding glycoprotein of the innate immune defense. Lf shows high bioavailability after oral administration, high selectivity toward cancer cells, and a wide range of molecular targets controlling tumor proliferation, survival, migration, invasion, and metastasization. Of note, Lf is able to promote or inhibit cell proliferation and migration depending on whether it acts upon normal or cancerous cells, respectively. Importantly, Lf administration is highly tolerated and does not present significant adverse effects. Moreover, Lf can prevent development or inhibit cancer growth by boosting adaptive immune response. Finally, Lf was recently found to be an ideal carrier for chemotherapeutics, even for the treatment of brain tumors due to its ability to cross the blood-brain barrier, thus globally appearing as a promising tool for cancer prevention and treatment, especially in combination therapies.

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Section: Lactoferrin and Cancermentioning

confidence: 99%

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

et al. 2020

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“…Many different drug regimens induce the CAC model, which have different rates of tumor formation and different times of tumor onset. Azoxymethane (AOM) + DSS, DMH + DSS, AOM/DMH + trinitrobenzenesulfonic acid are the 3 most commonly used modeling methods [23][24][25]. Although DSS + AOM is widely used, AOM is expensive and highly toxic and has high transportation requirements.…”

mentioning

confidence: 99%

Effect of TLR2 on the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer

Meng

Li²,

Zang³

et al. 2020

Cancer Cell Int

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Background: Colitis-associated cancer (CAC) is a complication of inflammatory bowel disease (IBD) with a poor prognosis because it is often diagnosed in advanced stages with local progression or metastasis. Compared with the more common polyp-induced sporadic colorectal cancer (sCRC), CAC has different molecular mechanisms. Toll-like receptor 2 (TLR2) expression is not limited to cells related to inflammation and immune function. High levels of TLR2 expression in tumor tissues of colorectal cancer (CRC) patients have been reported. This report is to investigate the effects of knockout and knockdown of the TLR2 gene on the proliferation of CAC and sCRC. Methods: Twelve C57BL/6 J wild-type mice (WT) and 12 TLR2 knockout mice (TLR2-/-) were used to rapidly establish a colitis-associated cancer (CAC) model via the 1,2-dimethylhydrazine-dextran sodium sulfate (DMH-DSS) method and were divided into the normal WT control group (NC), TLR2 knockout control group (KC), normal wild-type tumor modeling group (NT), and TLR2 knockout tumor modeling group (KT), with 6 mice in each group. The general performance of the mice during modeling, the gross changes of the colon and the rectum, and the pathological score of HE staining were used to observe tumor growth. The expression of TLR2 was detected by immunohistochemistry, and tumor proliferation was detected by Ki67 labeling. Lentivirus carrying TLR2-RNAi was used to stably infect colorectal cancer cells (HCT116 and HT29) to knock down TLR2 gene expression. The experimental groups included the uninfected control group, negative control group, and gene knockdown group. After infection, the expression of TLR2 protein was detected by Western blot, and cell proliferation and the cell cycle were detected by the CCK-8 method and fluorescence-activated cell sorting. Western blot was used to detect the expression levels of p-NF-κβ, cyclin D1 and cyclin D3 protein in each group of cells. Results: TLR2 knockout in the CAC model resulted in greater changes in body weight and more severe diarrhea and colorectal hemorrhage. However, knocking out the TLR2 gene reduced the shortening of colorectal length, the number of tumors, and the total tumor volume and inhibited the growth of CAC. Knocking out the TLR2 gene also reduced the pathological score and tumor severity. TLR2 was localized in the cell membrane of the colorectal epithelium of the NC group and of the colorectal tumors of the NT group and was highly expressed in the NT group, while antigen Ki67 was localized in the nucleus of the colorectal tumor cells of the NT group and the KT group, and its expression was reduced in the KT group. In an in vitro sporadic colorectal cancer cell experiment, TLR2 protein in the TLR2 knockdown group was significantly downregulated, and TLR2 knockdown significantly inhibited the

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“…Lf can target cells colon cancer cells and may internalize itself utilizing these receptors regulated by intestinal epithelial cells [ 57 ]. Liposomal bovine Lf was able to inhibit the expression of TNF-α mRNA expression in colorectal RKO and RCN-9 cells resulting in a lower inflammation, as demonstrated by reduced numbers of neutrophils associated with suppression of colorectal polyps [ 184 ]. In a study by Kanwar et al, alginate coated, chitosan conjugated, calcium phosphate, Fe saturated bLf nanocapsules (AEC-CCo-CP-Fe-bLf NCs) with a size of 396.1 nm were effective against triple positive cancer stem like Caco-2 cells [ 14 ].…”

Section: Pharmaceutical Applicationsmentioning

confidence: 99%

Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand

et al. 2020

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Recent progress in protein-based nanomedicine, inspired by the success of Abraxane® albumin-paclitaxel nanoparticles, have resulted in novel therapeutics used for treatment of challenging diseases like cancer and viral infections. However, absence of specific drug targeting, poor pharmacokinetics, premature drug release, and off-target toxicity are still formidable challenges in the clinic. Therefore, alternative protein-based nanomedicines were developed to overcome those challenges. In this regard, lactoferrin (Lf), a glycoprotein of transferrin family, offers a promising biodegradable well tolerated material that could be exploited both as an active therapeutic and drug nanocarrier. This review highlights the major pharmacological actions of Lf including anti-cancer, antiviral, and immunomodulatory actions. Delivery technologies of Lf to improve its pries and enhance its efficacy were also reviewed. Moreover, different nano-engineering strategies used for fabrication of drug-loaded Lf nanocarriers were discussed. In addition, the use of Lf for functionalization of drug nanocarriers with emphasis on tumor-targeted drug delivery was illustrated. Besides its wide application in oncology nano-therapeutics, we discussed the recent advances of Lf-based nanocarriers as efficient platforms for delivery of anti-parkinsonian, anti-Alzheimer, anti-viral drugs, immunomodulatory and bone engineering applications.

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Inhibition of DMH‑DSS‑induced colorectal cancer by liposomal bovine lactoferrin in rats

Cited by 22 publications

References 36 publications

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

Lactoferrin’s Anti-Cancer Properties: Safety, Selectivity, and Wide Range of Action

Effect of TLR2 on the proliferation of inflammation-related colorectal cancer and sporadic colorectal cancer

Lactoferrin, a multi-functional glycoprotein: Active therapeutic, drug nanocarrier & targeting ligand

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