Exploring the surprising connection between SARS-CoV-2 spike protein and cervical cancer cell growth inhibition through scientific research findings.
When SARS-CoV-2 emerged in 2019, it unleashed a global race to understand its biological effects. While most attention focused on the virus's respiratory impacts, a group of scientists began investigating a surprising potential connection: how the virus's signature spike protein might interact with cancer cells. What they discovered challenged conventional thinking and opened new avenues for understanding the complex relationship between viruses and cancer.
The spike protein, which forms the distinctive "crown" on the virus's surface, serves as the key that allows SARS-CoV-2 to enter our cells. As vaccines using this protein were developed, researchers grew curious about its potential effects on various biological processes, including cancer growth 1 3 .
The key that allows SARS-CoV-2 to enter human cells
Almost all cases are caused by human papillomavirus (HPV)
To understand this research, we must first appreciate what the spike protein is and how it functions. The spike protein is a complex structural protein that forms protruding knobs on the virus's outer envelope. It consists of two main subunits: S1, which contains the receptor-binding domain that latches onto human ACE2 receptors, and S2, which manages the fusion process that allows viral entry into cells 6 .
This protein is remarkably versatile in its ability to bind to multiple human receptors. Beyond the well-known ACE2 receptor, research indicates it can also interact with neuropilin-1 (NRP-1), a protein that normally binds to vascular endothelial growth factor (VEGF-A) and plays important roles in both nerve function and blood vessel formation . This versatility suggests the spike protein may influence various biological pathways beyond viral entry.
When SARS-CoV-2 vaccines were developed, many utilized genetic instructions (mRNA) that allow our cells to temporarily produce the spike protein, triggering an immune response without the actual virus. This approach raised questions among scientists: if the spike protein is being produced throughout the body, what other effects might it have? This question became particularly intriguing for cancer researchers 1 3 .
In a fascinating twist that defied expectations, researchers at Des Moines University and the University of Missouri made a surprising discovery in 2024. Their experiments revealed that rather than promoting cancer growth, the SARS-CoV-2 spike protein actually inhibited the growth of cervical cancer cells and induced apoptosis (programmed cell death) 1 3 .
Beyond simply reducing cell numbers, the spike protein actively triggered programmed cell death. The approximately three-fold increase in key apoptotic markers provided strong evidence that the spike protein was not just slowing cancer growth but actively engaging cell death pathways 3 .
Cervical cancer represents an ideal model for studying viral impacts on cancer because we already know that almost all cases are caused by another virus—the human papillomavirus (HPV). This established relationship between viruses and cervical cancer development made it a logical starting point for investigating potential connections with SARS-CoV-2 3 .
Additionally, while ACE2 receptors (the spike protein's primary entry point) show only modest expression in the cervix, research has confirmed that spike proteins can utilize alternative receptors to exert effects on cells, making the cervical cancer investigation biologically plausible 3 6 .
To thoroughly investigate how the spike protein affects cervical cancer cells, researchers designed a comprehensive experiment using the SiHa cervical cancer cell line, which is widely used in cancer research. Their approach methodically examined multiple aspects of cell behavior when exposed to the spike protein 3 .
Researchers grew SiHa cervical cancer cells in laboratory conditions until they reached 70% confluence, indicating active growth phase 3 .
The cells were treated with purified SARS-CoV-2 spike protein at varying concentrations (10, 20, 50, and 200 ng/ml) for 72 hours. A control group received only culture medium for comparison 3 8 .
After treatment, 1,000 cells from each group were plated in Petri dishes and allowed to grow for 9 days. This test measures how many cells retain the ability to form colonies, indicating their reproductive capacity 3 .
Researchers used a colorimetric assay that measures mitochondrial dehydrogenase activity, which directly correlates with the number of viable, proliferating cells 3 .
Multiple methods were employed:
Using RT-PCR and immunohistochemistry, the team examined changes in key regulatory molecules, particularly p53 (a tumor suppressor) and TRAIL (a pro-apoptotic factor) 3 .
This multi-faceted approach allowed researchers to observe not just whether the spike protein affected cancer cells, but how it achieved these effects at a molecular level.
| Molecule | Function | Change After Spike Exposure |
|---|---|---|
| p53 | Tumor suppressor protein | Upregulated 2.2-fold |
| TRAIL | TNF-related apoptosis-inducing ligand | Upregulated 2.5-fold |
| PCNA | Proliferating cell nuclear antigen | Downregulated 60% |
The molecular analyses revealed the probable mechanism behind these effects. The significant upregulation of p53 (a critical tumor suppressor often called "the guardian of the genome") and TRAIL (a potent inducer of apoptosis) suggested that the spike protein was activating the cells' own anti-cancer defenses 1 3 .
| Research Tool | Specific Type/Product | Function in the Experiment |
|---|---|---|
| Cell Line | SiHa cervical cancer cells | Model system for studying cervical cancer biology |
| Spike Protein | Wild-type S1+S2 SARS-CoV-2 SP (BioLegend) | The key variable being tested |
| Culture Medium | DMEM with 10% FBS and 1% penicillin-streptomycin | Optimal cell growth conditions |
| Detection Assay | Clonogenic cell survival assay | Measures long-term reproductive capacity |
| Apoptosis Kit | Chemicon ApopTag TUNEL assay | Labels DNA breaks in dying cells |
| Caspase Test | BioVision caspase-3 colorimetric assay | Quantifies apoptosis execution |
| Molecular Analysis | RT-PCR for p53 and TRAIL | Measures gene expression changes |
While the cervical cancer findings pointed toward anti-cancer effects, the broader scientific picture appears more complex. Research on other cancer types has revealed potentially contradictory effects, highlighting that the spike protein's impact may depend heavily on context.
A 2024 study published in Oncotarget found that in certain lung and breast cancer cells, the spike protein could actually suppress p53 activity, potentially protecting cancer cells from death. This research showed that spike protein expression interrupted the interaction between p53 and MDM2 (a protein that regulates p53 degradation) and reduced activation of p53-target genes involved in growth arrest and apoptosis 4 .
This contradiction illustrates a fundamental principle in biology: context matters. The same molecule can have different effects in different cell types or under different conditions. As the Oncotarget study authors noted, "SARS-CoV-2 spike reduces chemotherapy-induced p53 transcriptional activity in cancer cells," which could potentially make some cancers more resistant to treatment 4 .
These seemingly contradictory findings don't necessarily invalidate either set of results—rather, they highlight the complexity of biological systems and the danger of oversimplifying scientific conclusions. The spike protein may indeed inhibit certain cancers while potentially promoting conditions favorable to others, or its effects may depend on additional factors such as:
The research exploring relationships between SARS-CoV-2 spike protein and cancer represents early-stage investigative science. The compelling evidence that spike protein can inhibit cervical cancer growth by activating p53 and TRAIL pathways offers fascinating insights but requires further validation.
Laboratory findings don't yet translate to clinical recommendations
Potentially protective in some contexts while possibly problematic in others
Need to explore mechanisms in more complex models and clinical settings
The researchers behind the cervical cancer study appropriately caution that "further studies are needed to elaborate on the potential effects of the SARS-CoV-2 spike protein on other cancer cell lines and normal physiological cell lines for comparison" 1 3 . Future research will need to explore these mechanisms in more complex models and ultimately in clinical settings.
What makes this story particularly compelling is how it exemplifies the unexpected directions science can take—from understanding a dangerous virus to potentially uncovering new avenues for cancer research. As this field advances, it may eventually yield insights that benefit both infectious disease treatment and oncology, proving that even in challenging times, scientific curiosity continues to light a path forward.