Mayapple (Podophyllum peltatum)

As stated above, modern cancer treatments often target the cell replication process in an effort to stop cancer cells from replicating, arresting the growth of the tumor. Human cells (other than sperm and egg cells) replicate through a process called mitosis. During mitosis, the cell generates a copy of its DNA, condenses that DNA into a structure called a chromosome, then splits those chromosomes in half, and pulls the identical halves to either end of the cell. At that point, the cell splits into two, with each new daughter cell containing the same genetic information as the original parent cell. Within this process, the point at which the half-chromosomes, or chromatids, are pulled to separate ends of the cell requires a structure called a mitotic spindle which serves as the rope that both anchors the chromatids to each end of the cell, and which pulls them to that end.

Etoposide is being investigated as a chemotherapeutic agent that works by inhibiting the ability of cells to create tubulin, the protein that makes up the metaphorical fibers of the metaphorical rope of those mitotic spindles.⁵ Without these proteins, the mitotic spindles cannot form, and without the mitotic spindles, the cell cannot replicate. This leads to the arrest of tumor growth.

Use of etoposide as a chemotherapeutic is currently limited for three primary reasons. First, it is myelosuppressive.⁶ This means that it attacks bone marrow, which limits the body’s ability to produce red blood cells (necessary for the circulation of oxygen) and white blood cells (necessary for the maintenance and function of the immune system). Similar to other chemotherapeutic drugs, there have been clinical cases where tumors have developed drug-resistance to etoposide, limiting its long-term efficacy.⁷ Lastly, etoposide, like other chemotherapeutics, does not only damage cancer cells, but damages and kills healthy body cells as well. Nevertheless, researchers are continuing to investigate etoposide as a means of using chemotherapy against tumors that have grown resistant to the more commonly applied chemotherapeutic treatments.⁸

Research on etoposide in managing cytokine storm syndrome

Further research is exploring the potential application of etoposide as an intervention to mitigate the effects of cytokine storm syndrome. Cytokine storm syndrome is a process by which a person’s immune system recognizes a threat (e.g., a virus, like COVID-19, or an accumulation of dead or infected cells, resulting in sepsis), and launches an immune response.⁹ This immune response particularly releases cytotoxic t-cells, which are a type of white blood cell that will destroy damaged or infected cells within the body as a method of preventing the further spread of the inciting threat. However, in some cases (particularly in cases like COVID-19), this means that this immune response ends up destroying more cells than the body can afford to lose, potentially resulting in organ failure, and sometimes, death.¹⁰

Etoposide, when administered in clinical settings, has demonstrated a capacity to kill some of the cytotoxic t-cells during a cytokine storm, slowing down organ deterioration and giving clinicians time to administer alternative drugs and treatments to address the primary cause of the cytokine storm.¹¹

Based on this preliminary evidence and the lack of information available about COVID-19 and potential available treatments at the time, a team of clinicians documented their use of etoposide for a patient experiencing multiple complications due to COVID-19, including cytokine storm syndrome, in 2020.¹² There were a number of interventions with more supporting evidence that these care providers attempted to administer over the course of the patient’s first 20 days in the hospital, but as the patient’s condition continued to deteriorate, they turned to etoposide. They administered two doses of etoposide, one week apart, and after another five days, the patient improved enough to be transferred out of the ICU. Later they were able to adequately breathe on their own, so they were removed from the ventilator, underwent physical therapy, and were later released from the hospital.¹³

This is a single case study, meaning no broad conclusions about the use of etoposide in the management of COVID-19 and cytokine storm syndrome should be drawn at this juncture. Nevertheless, future research will likely continue to explore the use of etoposide in the management of these conditions and reach a more definitive conclusion.

Cautions:

All parts of the Mayapple plant are poisonous except for the fully ripe fruit.¹⁴ The roots, leaves, stems, seeds, and underripe fruit is toxic to humans, cattle, and swine, and could lead to severe bowel discomfort and vomiting.¹⁵ Exercise extreme caution when harvesting mayapple fruit to eat, and consult multiple sources to identify the plant and to verify the ripeness of the fruit.