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

Sep 21, 2026

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Cancer causes over 10 million deaths annually worldwide, yet many conventional therapies can harm normal tissues through toxic side effects. Caseins and their derivatives demonstrate antitumor and cytotoxic activity across multiple tumor types while avoiding damage to normal cells. Evidence synthesized in this work links anticancer effects to defined molecular mechanisms, including STAT1/interferon enhancement, reduced CD44 stemness, STAT3/HIF1-α attenuation, decreased uPAR and PAI-1 expression, mitochondrial dysfunction with lower ATP, increased caspase-3 activity, and inhibition of TLR4/NF-кB signaling.

LanguageEnglish

CategoryResearch & Report

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Pages13

Reading Time33 min

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Abstract

Introduction

Milk composition

Medical Oncology (2024) 41:200 [https://doi.org/10.1007/s12032-024-02403-8](https://doi.org/10.1007/s12032-024-02403-8) Anti‑cancer potential of casein and its derivatives: novel strategies for cancer treatment Daniel Romero‑Trejo1 · Itzen Aguiñiga‑Sanchez1,2 · Edgar Ledesma‑Martínez1 · Benny Weiss‑Steider1 · Edith Sierra‑Mondragón3 · Edelmiro Santiago‑Osorio1 Received: 12 March 2024 / Accepted: 2 May 2024 / Published online: 11 July 2024 © The Author(s) 2024 Abstract 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. Keywords Milk protein · Casein · Cancer · Apoptosis · Signaling pathways Introduction In 2020, the World Health Organization (WHO) reported 18.1 million cancer cases, and 9.6 million cancer deaths in 2018, with a projected increase to 29.4 million cases in 2040. The highest incidence among males was observed for lung cancer (14.3%), prostate cancer (14.1%), and colorectal cancer (10 .6%) . For females, breast cancer (24 .5%), colorectal * Edelmiro Santiago-Osorio [edelmiro@unam.mx](edelmiro@unam.mx) 1 Hematopoiesis and Leukemia Laboratory, Research Unit on Cell Differentiation and Cancer, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, 09230 Mexico City, Mexico 2 Department of Biomedical Sciences, School of Medicine, Faculty of High Studies Zaragoza, National Autonomous University of Mexico, 56410 Mexico City, Mexico 3 Department of Physiology, Biophysics, and Neurosciences, Center for Research and Advanced Studies of the National Polytechnic Institute, 07360 Mexico City, DF, Mexico cancer (9.4%), and lung cancer (8.4%) were most frequently affected being a global health problem. In both sexes, lung, breast, and colorectal cancer are the leading causes of death worldwide by cancer [1] . Although 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. Despite knowledge of the genetic basis and molecular mechanisms ofthis disease, cancer remains a highly aggressive pathology with a high mortality rate. This is primarily due to chemoresistance developed by tumor cells, metastasis formation, and the highly cytotoxic side effects in normal tissues [2–4] . Therefore, there is an urgent need to study new therapeutic molecules that can eradicate cancer cells while minimizing toxic side effects on healthy organs. In this regard, bioactive peptides obtained from milk show promise as antitumor agents, limiting the growth of cancer cells and, at the same time, positively influencing immune sys

FAQs

Why are researchers seeking selective cancer therapies?

Current cancer treatments often produce toxic side effects in normal tissues. This drives the search for approaches that selectively eliminate cancer cells while minimizing harm to healthy cells.

What anticancer mechanisms are linked to caseins and their derivatives?

Reported mechanisms include enhanced STAT1/interferon signaling, suppression of CD44 stemness markers, reduced STAT3/HIF1-α signaling, down-expression of uPAR and PAI-1, mitochondrial membrane potential loss with reduced ATP, increased caspase-3 activity, and inhibition of TLR4/NF-кB signaling.

What is the proposed therapeutic role of casein?

The findings support the conclusion that casein could be an effective adjuvant for cancer treatment based on its antitumor potential and cytotoxic effects on cancer cells.

Sep 21, 2026

Uploaded by Aria