Anticancer Treatment in Vitro and in Vivo

Extracts of St John’s wort have been studied in vitro, and, to a limited extent, in vivo, for the treatment of cancer. Several studies, for example, demonstrated that hyperoside, a flavanol glycoside present in plants of the Hypericum genera, induces autophagy and/or apoptosis in human non–small cell lung and pancreatic cancer cells.7,8 Hyperoside treatment also inhibited tumor growth in mouse models with human lung or pancreatic cancer xenografts.8,9

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St John’s wort extract has also been studied as a photosensitizer as a treatment for some tumor types. An in vitro study demonstrated that hypericin, an extract from St John’s wort, combined with photodynamic therapy (PDT) resulted in cell death due to apoptosis in both pigmented and unpigmented human melanoma cells.10 Other studies also found that hypericin treatment induced apoptosis in human squamous cell carcinoma cells and human bladder cells after application of PDT.11,12

One single-arm, in-human study evaluated St John’s wort applied as a topical extract to non-melanoma skin cancers of 34 patients, including actinic keratosis, basal cell carcinoma, and morbus Bowen.13 Lesions were irradiated 2 hours after application of the extract, and the combined extract plus PDT was administered weekly for a mean of 6 weeks.

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Complete clinical response was observed among 50% of patients with actinic keratosis, 28% of patients with superficial BCC, and 40% of patients with Bowen disease. Complete histologic response occurred in 11% and 80% of patients with superficial BCC and Bowen disease, respectively.

Radiation-induced Toxicity

A case report of a patient who received radiation for adjunctive treatment of head and neck squamous cell carcinoma suggested that St John’s wort supplementation may result in an unusually intensive skin reaction that resolved after discontinuation.14 Though the authors noted that the mechanism is unknown, they hypothesized that it could be explained by the photosensitizing effects of St John’s wort.

Conclusions

There are few in-human studies that have evaluated the effect of St John’s wort as an anticancer agent or a preventative against treatment-related toxicities. In vivo studies suggest that extracts of St John’s wort may have apoptotic effects on cancer cells, but human studies have not been conducted to test this hypothesis. In vitro data indicate that St John’s wort extract is a photosensitizer that induces cell death when combined with PDT, but a small in-human pilot study demonstrated modest benefit with the combination.

Importantly, St John’s wort induces CYP3A4 expression, which can alter the plasma levels of some anticancer agents, such as irinotecan and docetaxel, and a case report suggests that it may enhance skin sensitivity to radiation therapy. St John’s wort, therefore, should be used with caution among some patients, depending on their anticancer regimen.

References

  1. St. John’s wort. National Institutes of Health website. https://nccih.nih.gov/health/stjohnswort/ataglance.htm. Updated September 2016. Accessed October 2, 2017.
  2. Kober M, Pohl K, Efferth T. Molecular mechanisms underlying St. John’s wort drug interactions. Curr Drug Metab. 2008;9:1027-37.
  3. Satia JA, Littman A, Slatore CG, Galanko JA, White E. Associations of herbal and specialty supplements with lung and colorectal cancer risk in the VITamins And Lifestyle (VITAL) Study. Cancer Epidemiol Biomarkers Prev. 2009;18:1419-28. doi: 10.1158/1055-9965.EPI-09-0038
  4. Brasky TM, Lampe LW, Potter JD, Patterson RE, White E. Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) Cohort. Cancer Epidemiol Biomarkers Prev. 2010;19:1696-708. doi: 10.1158/1055-9965.EPI-10-0318
  5. Mathijssen RH, Verweij J, de Bruijn P, Loos WJ, Sparreboom A. Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst. 2002;94:1247-9.
  6. Goey AK, Meijerman I, Rosing H, et al. The effect of St John’s wort on the pharmacokinetics of docetaxel. Clin Pharmacokinet. 2014;53:103-10. doi: 10.1007/s40262-013-0102-5
  7. Fu T, Wang L, Jin X, Sui HJ, Liu Z, Jin Y. Hyperoside induces both autophagy and apoptosis in non-small cell lung cancer cells in vitro. Acta Pharmacologica Sinica. 2016;37:505-18. doi: 10.1038/aps.2015.148
  8. Li Y, Wang Y, Li L, et al. Hyperoside induces apoptosis and inhibits growth in pancreatic cancer via Bcl-2 family and NF-κB signaling pathway both in vitro and in vivo. Tumour Biol. 2016;37:7345-55. doi: 10.1007/s13277-015-4552-2
  9. Liu YH, Liu GH, Mei JJ, Wang J. The preventive effects of hyperoside on lung cancer in vitro by inducing apoptosis and inhibiting proliferation through caspase-3 and P53 signaling pathway. Biomed Pharmacother. 2016;83:381-91. doi: 10.1016/j.biopha.2016.06.035
  10. Kleemann B, Loos B, Scriba TJ, Lang D, DAvids LM. St John’s wort (Hypericum perforatum L.) photomedicine: hypericin-photodynamic therapy induces metastatic melanoma cell death. PLoS ONE. 2014;9:e103762. doi: 10.1371/journal.pone.0103762
  11. Sharma KV, Davids LM. Hypericin-PDT-induced rapid necrotic death in human squamous cell carcinoma cultures after multiple treatment. Cell Biol Int. 2012;36:1261-6. doi: 10.1042/CBI20120108
  12. Stavropoulos NE, Kim A, Nseyo UU, et al. Hypericum perforatum L. extract – novel photosensitizer against human bladder cancer cells. J Photochem Photobiol B. 2006;84:64-9.
  13. Kacerovska D, Pizinger K, Majer F, Smid F. Photodynamic therapy of nonmelanoma skin cancer with topical hypericum perforatum extract–a pilot study. Photochem Photobiol. 2008;84:779-85. doi: 10.1111/j.1751-1097.2007.00260.x
  14. Putnik K, Stadler P, Schafer C, Koelbl O. Enhanced radiation sensitivity and radiation recall dermatitis (RRD) after hypericin therapy – case report and review of literature. Radiat Oncol. 2006;1:32. doi: 10.1186/1748-717X-1-32

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