Praziquantel-50

PZQ-50, Praziquantel

Summary of Key Functions:

Anti-parasitic:

Praziquantel has two main therapeutic pharmacological effects on the worms it is effective against:

1. Spastic paralysis occurs when the muscles of the worms contract rigidly. The body tension of Schistosoma japonicum increases only 20 seconds after exposure to praziquantel at low concentration. The contraction of worm muscle is related to the increase of membrane permeability by praziquantel and the loss of intracellular calcium ions.
2. Cortical damage and immune function are involved in killing the worms. Praziquantel has a rapid and obvious damage to the worm’s outer body cortex, causing the syncytial outer skin to swell forming vacuoles leading to the development of bullae which then protrude from the body surface.  Eventually the epidermis erodes due to ulceration leading to the circular and longitudinal muscles dissolveing rapidly. In human body, vacuolar degeneration of the epidermis was observed within 15 minutes after administration.

After the destruction of the cortex, the absorption and excretion of the parasite are affected. More importantly, the exposure of its surface antigen makes it vulnerable to human immune attack. A large number of eosinophils attach to the lesions and invade the parasite, which leads to its death.

Anti-Cancer

Praziquantel applied to the cancer treatment model, has the following three demonstrated actions:

1. Cellular level calcium ion influx resulting in cellular contraction of the cancer cells causing spastic paralysis. 
2. The cell membrane of the cancer cells is damaged allowing the body’s own immune function to activate and begin the apoptosis process of cellular death with the cancer cells.
3. Cancer cell membrane depolarization resulting in a significant decrease in alkaline phosphatase activity which then inhibits the uptake of glucose resulting in endogenous glycogen depletion and ultimate starvation of the cancer cells.

References

1. Wu et al. (2012). “Praziquantel Synergistically Enhances Paclitaxel Efficacy to Inhibit Cancer Cell Growth.” PLOS One. DOI: 10.1371/journal.pone.0051776. This study demonstrated PZQ’s synergistic enhancement of PTX in various cancer cell lines and mouse models, highlighting XIAP down-regulation. Available at: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0051776.ncbi.nlm.nih.govpmc.ncbi.nlm.nih.govjournals.plos.org
2. Kamsa-ard et al. (2015). “Association between Praziquantel Treatment and Cholangiocarcinoma: A Hospital-Based Matched Case–Control Study.” BMC Cancer. DOI: 10.1186/s12885-015-1779-0. This study noted an association between repeated PZQ use and CCA risk, suggesting caution in endemic areas. Available at: https://bmccancer.biomedcentral.com/articles/10.1186/s12885-015-1779-0.bmccancer.biomedcentral.comncbi.nlm.nih.gov
3. Ketkar (1982). “Praziquantel Results in the Carcinogenic Potency Database.” Toxicology. Reported weak carcinogenic potential in female hamsters at high doses, but inconclusive for humans. Available via: https://toxnet.nlm.nih.gov.toxnet.nlm.nih.gov
4. Imperiale et al. (2023). “Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?” Cancers. Discusses PZQ’s synergistic effects with PTX and the broader trend of repurposing anthelmintics for cancer. Available at: https://www.mdpi.com/2072-6694/13/13/3193.mdpi.com
5. Pourgholami et al. (2009). “Repurposing of Approved Non-Oncology Drugs for Cancer Therapy.” European Journal of Medical Research. Mentions PZQ’s potential in combination with PTX, emphasizing its role in enhancing apoptosis. Available at: https://eurjmedres.biomedcentral.com/articles/10.1186/s40001-023-01367-y
6. Wu, G. (2020). Praziquantel and albendazole pills can cure cancer. Journal of Advances in Medicine Science, 3(1), 38-45. https://doi.org/10.30564/jams.v3i1.1365
7. Guilford, F. T., & Yu, S. (2019). Antiparasitic and antifungal medications for targeting cancer cells: Literature review and case studies. Alternative Therapies in Health and Medicine, 25(4), 26-31. PubMed PMID: 31202208. https://todayspractitioner.com/wp-content/uploads/2019/08/Guilford.pdf
8. Pfab, C.; Schnobrich, L.; Eldnasoury, S.; Gessner, A.; El-Najjar, N. Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know? Cancers 2021, 13, 3193. https://doi.org/10.3390/cancers13133193