By Marilena Antunes-Ricardo, Ana Carolina Martínez Torres y Patricia Martínez Morales
The nopal, a plant endemic to Mexico, has been deeply connected to the country’s history and culture since pre-Hispanic times. It has also shown promise as a functional food, offering multiple health benefits, including being a source of compounds with chemopreventive effects.
In Mexico, cancer is reported as the third leading cause of death, accounting for 12% of all fatalities. Among the various types of cancer, colon cancer is the third most prevalent and the second most deadly, affecting women more frequently than men.
To date, surgery remains the primary treatment option, typically accompanied by chemotherapy as an adjuvant therapy.
However, alternative therapies are being explored, such as those aimed at directly inhibiting cellular proliferation, differentiation, and migration and immunotherapies that assist the immune system in targeting tumor cells.
Immunogenic Cell Death (ICD)
The immune system plays a critical role in tumor progression and development, as well as in its elimination and control.
On one hand, tumor progression can trigger chronic inflammation, characterized by the infiltration of immune cells into the tumor site. This promotes cancer development by inducing proliferation, survival, angiogenesis, and metastasis of cancer cells.
On the other hand, immune surveillance prevents cancer cells from establishing themselves and growing. Furthermore, cells can release signals that activate immune memory specific to the tumor when cells die, preventing cancer recurrence. This process is known as immunogenic cell death (ICD).
ICD is a regulated mechanism of cell death capable of activating an adaptive immune response to endogenous or exogenous antigens expressed by dying cells, such as tumor neoantigens. This type of cell death has been proposed as an alternative approach to restoring the immune response against tumors and targeting cancer cells by inhibiting their acquired immune suppression and tolerance mechanisms.
The mechanism of ICD involves the induction of endoplasmic reticulum (ER) stress to promote the exposure or release of damage-associated molecular patterns (DAMPs). A key characteristic of ICD is the exposure and release of DAMPs, which are recognized by pattern recognition receptors (PRRs) that alert the body to a state of danger, triggering the activation of an immune response and establishing immune memory.
Chemotherapeutic agents, radiation therapy, hypericin-based photodynamic therapy, and certain natural substances can stimulate ICD.
Activating ICD with natural molecules may offer a promising alternative for preventing and treating neoplastic diseases. Despite these benefits, few natural compounds have been explored as triggers of immunogenic cell death.
Nopal and the Immune System
Nopal is exceptionally resilient, thriving in drought and extreme temperatures. Recognized for its potential, the Food and Agriculture Organization (FAO) has called it: “food of the future”.
Historically, it has been recognized as a medicinal plant, commonly used as an adjunct in treating diabetes, cancer, high triglycerides and cholesterol levels, inflammation, obesity, and wound healing, among many other conditions.
In vitro and in vivo studies with various nopal extracts have demonstrated its potential antitumor effects on several cancer cell lines, particularly those related to colon cancer.
Additionally, nopal extracts have shown potent anti-inflammatory effects by modulating the production of different inflammatory biomarkers such as prostaglandins (PGE2), tumor necrosis factor-alpha (TNF-α), interleukins IL-1B and IL-6, as well as activating antioxidant enzymes like catalase (CAT), superoxide dismutase (SOD), and glutathione reductase (GSH), which are involved in the inflammatory cascade, such as cyclooxygenase (COX)-2, nitric oxide synthase (NOS), and myeloperoxidase.
This ability to modulate the inflammatory response to various stimuli —combined with its potential to induce cancer cell death— suggests that nopal may act as an inducer of immunogenic cell death and activate the antitumor immune response.
Research Status.
A research team from the Tecnológico de Monterrey, the Universidad Autónoma de Nuevo León (UANL), and the Benemérita Universidad Autónoma de Puebla (BUAP) is currently investigating whether nopal (Opuntia ficus-indica) can selectively exhibit antitumor effects on colon cancer cells by activating immunogenic cell death, and identifying which compounds might be responsible for this activity.
With this multidisciplinary approach, the project aims to establish scientific foundations for developing new strategies to combat various diseases, opening up broad possibilities in therapeutics, clinical nutrition, and the food industry.
This project is currently funded by the National Council of Humanities, Sciences, and Technologies (Conacyt), CF-2023-G-669, titled “Activation of the Antitumor Immune Response Induced by Compounds in Nopal (Opuntia ficus-indica) on Colorectal Cancer Cells,” approved under the “Science of the Border 2023” call.
References
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Authors
Marilena Antunes-Ricardo, Research Professor at the Institute for Obesity Research (IOR), Tecnológico de Monterrey, Monterrey campus.
Ana Carolina Martínez Torres, Research Professor and Coordinator of the PhD Program in Immunobiology at the Universidad Autónoma de Nuevo León (UANL).
Patricia Martínez-Morales, CONACYT Researcher for Mexico at the Faculty of Biological Sciences, Benemérita Universidad Autónoma de Puebla (BUAP), Puebla.
