Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model

Ledesma‐Martínez, Edgar; Pérez-Cordero, Claudia Leticia; Córdova-Galaviz, Yolanda; Sánchez-Tellez, Guadalupe; Huerta-Yépez, Sara; Aguíñiga-Sánchez, Itzen; Miranda-Peralta, Enrique; García, Alberto Monroy; Weiss‐Steider, Benny; Santiago‐Osorio, Edelmiro

doi:10.3892/ol.2012.758

Cited by 11 publications

(11 citation statements)

References 18 publications

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“…Epicatechin was reported to promote the bone marrow cells proliferation, encouraged myeloid colonies development from them and improved the IL‐3 effect to raise the colony forming‐unit amounts in culture (Takano, Tanaka, Tsukamoto, Yahagi, & Fushiya, ). WEHI‐3B cells migrated to the bone marrow starting from 24 hr post‐inoculation, indicating their aggressive invasion to secondary sites, and causing 100% animal mortality within 30 days (Ledesma‐Martínez et al, ). Here, the M. citrifolia leaf extract showed hematopoiesis inductive effect, while inducing leukemia cells apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Epicatechin and scopoletin‐rich Morinda citrifolia leaf ameliorated leukemia via anti‐inflammatory, anti‐angiogenesis, and apoptosis pathways in vitro and in vivo

et al. 2019

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The anti‐leukemia mechanisms of Morinda citrifolia L. leaf extract were investigated on human Jurkat leukemia cells and in leukemia‐induced BALB/c mice. The leukemia‐induced mice were fed daily with the extract (100 or 200 mg/kg BW) and compared to ATRA (All‐trans‐retinoic‐acid; 5 mg/kg BW). After 4 weeks’ treatment, the extract (standardized to epicatechin and scopoletin), arrested Jurkat cell‐cycle at the G0/G1 phase and activated the caspase‐3 and caspase‐8 (death‐receptor extrinsic pathways). The extract dose‐dependently reduced the blood and bone marrow myeloblasts levels of leukemia‐induced mice; upregulated cancer suppressor genes CSF3, SOCS1, PTEN and TRP53; increased anti‐inflammatory IL10 and IL4; downregulated anti‐apoptotic or proliferation genes; decreased the pro‐inflammatory NF‐κβ; suppressed pro‐angiogenesis VEGFA mRNA expressions, and restored the homeostatic immune or leukocytes levels. The extract directly ameliorated leukemia via cancer cells apoptosis, suppressed inflammation and angiogenesis; and mitigated bone marrow myeloblasts imbalance, without any observable toxicity on the animals. Practical applications The scopoletin (coumarin) and epicatechin (flavonoid)‐rich Morinda citrifolia (Noni) leaves may be used as functional food ingredient, vegetables, or dietary supplements to treat and suppress leukemia progression by directly killing the cancer cells and preventing new cancer cells development and bone marrow myeloblast imbalance in the bone marrow, without being toxic to normal cells. The M. citrifolia leaf extract suppressed inflammation, and potential metastasis by inhibiting new cancer‐related blood vessel formation.

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Section: Discussionmentioning

confidence: 99%

Epicatechin and scopoletin‐rich Morinda citrifolia leaf ameliorated leukemia via anti‐inflammatory, anti‐angiogenesis, and apoptosis pathways in vitro and in vivo

et al. 2019

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“…Over time, it has been shown that SC accelerates the transition of band cells from bone marrow to polymorphonuclear cells, thus inducing macrophage colony-stimulating factor (M-CSF) [37]. Bone marrow progenitor cells of mice cultured with interleukin 3 (rmIL-3) as a growth factor in the presence of SC show increased cell numbers that exceed 50% [38]. Consequently, the administration of SC every 48 h for 6 days in BALB/c mice has been shown to increase myeloid cell proliferation and the number of total and mononuclear cells from bone marrow, events that are considered indices of medullary haematopoiesis activation [36].…”

Section: Caseins As Regulators Of Haematopoiesis and The Immune Symentioning

confidence: 99%

“…The first evidence of the antileukaemic activity of protein milks was shown in vitro by SC inhibiting the proliferation of leukaemia in mouse cells, such as those from the WEHI-3, J774, and P388 cell lines, even inducing apoptosis in one of them: the WEHI-3 myelomonocytic leukaemia cell line. However, in mononuclear normal cells from BALB/c mice (MNCs) bone marrow, SC induces a marked proliferation stimulus [38]. The evidence showed that normal tissues could be less sensitive to the biological effects of new molecules with potential antileukaemic properties [104, 105]; these data are significant since the usefulness of a potential anticancer compound depends not only on its ability to induce cytotoxicity in malignant cells but also on its relative lack of ability to induce toxicity in normal tissues and, in the case of SC, its ability to suppress the proliferation and induce the death of leukaemia cells.…”

Section: Caseins and Peptides Derived From Caseins Have Antileukaementioning

confidence: 99%

“…It was later shown that SC injected i.p. into mice inoculated lethally with WEHI-3 myelomonocytic leukaemia cells reduced the tumour burden and suppressed hepatomegaly, which collectively increased the survival of the leukaemic mice to a significant extent [38]. Similarly, in mice inoculated with cells from the J774 leukaemia macrophage-like cell line, a model of macrophage-like tumour M5 AML, SC significantly reduced splenomegaly, hepatomegaly, and the presence of solid tumours [110].…”

Section: Caseins and Peptides Derived From Caseins Have Antileukaementioning

confidence: 99%

“…We know that SC administration in the peritoneal cavity promotes the survival of leukaemic mice [38, 110]. The possible mechanism of this antileukaemic effect may be due to the activation of TLRs by α -casein to exerting an antitumour activity (Figure 1(b)).…”

Section: Mechanism Of Action For Caseins and Derivate Peptides In mentioning

confidence: 99%

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Casein and Peptides Derived from Casein as Antileukaemic Agents

Ledesma‐Martínez

Aguíñiga-Sánchez

Weiss‐Steider

et al. 2019

Journal of Oncology

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Milk is a heterogeneous lacteal secretion mixture of numerous components that exhibit a wide variety of chemical and functional activities. Casein, the main protein in milk, is composed of α-, β-, and κ-caseins, each of which is important for nutritional value and for promoting the release of cytokines, also are linked to the regulation of haematopoiesis and immune response and inhibit the proliferation and induce the differentiation of leukaemia cells. It has been shown that the digestive process of caseins leads to the release of bioactive peptides that are involved in the regulation of blood pressure and the inhibition or activation of the immune response by serving as agonists or antagonists of opioid receptors, thus controlling the expression of genes that exert epigenetic control. Later, they bind to opioid receptor, block nuclear factor κ-beta, increase the redox potential, and reduce oxidative stress and the pro-inflammatory agents that favour an antioxidant and anti-inflammatory environment. Therefore, the bioactive peptides of casein could be compounds with antileukaemia potential. This review provides a summary of current knowledge about caseins and casein peptides on the immune system as well as their roles in the natural defence against the development of leukaemia and as relevant epigenetic regulators that can help eradicate leukaemia.

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Anti-cancer potential of casein and its derivatives: novel strategies for cancer treatment

Romero-Trejo,

Aguiñiga-Sanchez,

Ledesma-Martínez

et al. 2024

Med Oncol

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Cancer is one of the leading causes of death worldwide, with over 10 million fatalities annually. While tumors can be surgically removed and treated with chemotherapy, radiotherapy, immunotherapy, hormonal therapy, or combined therapies, current treatments often result in toxic side effects in normal tissue. Therefore, researchers are actively seeking ways to selectively eliminate cancerous cells, minimizing the toxic side effects in normal tissue. Caseins and its derivatives have shown promising anti-cancer potential, demonstrating antitumor and cytotoxic effects on cells from various tumor types without causing harm to normal cells. Collectively, these data reveals advancements in the study of caseins and their derivative peptides, particularly providing a comprehensive understanding of the molecular mechanism of action in cancer therapy. These mechanisms occur through various signaling pathways, including (i) the increase of interferon-associated STAT1 signaling, (ii) the suppression of stemness-related markers such as CD44, (iii) the attenuation of the STAT3/HIF1-α signaling, (iv) the down-expression of uPAR and PAI-1, (v) the loss of mitochondrial membrane potential and reduced intracellular ATP production, (vi) the increase of caspase-3 activity, and (vii) the suppression of TLR4/NF-кB signaling. Therefore, we conclude that casein could be an effective adjuvant for cancer treatment.

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Casein induces the proliferation of bone marrow mononuclear cells, apoptosis of WEHI-3 leukaemic cells and increased survival in a leukaemia mouse model

Cited by 11 publications

References 18 publications

Epicatechin and scopoletin‐rich Morinda citrifolia leaf ameliorated leukemia via anti‐inflammatory, anti‐angiogenesis, and apoptosis pathways in vitro and in vivo

Epicatechin and scopoletin‐rich Morinda citrifolia leaf ameliorated leukemia via anti‐inflammatory, anti‐angiogenesis, and apoptosis pathways in vitro and in vivo

Casein and Peptides Derived from Casein as Antileukaemic Agents

Anti-cancer potential of casein and its derivatives: novel strategies for cancer treatment

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