Interactions Between Natural Products and Cancer Treatments: Underlying Mechanisms and Clinical Importance

Overview

Journal Cancer Chemother Pharmacol

Specialty Oncology

Date 2023 Jan 27

PMID 36707434

Authors

Wai-Jo Jocelin Chan

Jeffry Adiwidjaja

Andrew J McLachlan

Alan V Boddy

Joanna E Harnett

Affiliations

Soon will be listed here.

Abstract

Natural products, also referred to as dietary supplements, complementary and alternative medicines, and health or food supplements are widely used by people living with cancer. These products are predominantly self-selected and taken concurrently with cancer treatments with the intention of improving quality of life, immune function and reducing cancer symptoms and treatment side effects. Concerns have been raised that concurrent use may lead to interactions resulting in adverse effects and unintended treatment outcomes. This review provides an overview of the mechanisms by which these interactions can occur and the current evidence about specific clinically important natural product-drug interactions. Clinical studies investigating pharmacokinetic interactions provide evidence that negative treatment outcomes may occur when Hypericum perforatum, Grapefruit, Schisandra sphenanthera, Curcuma longa or Hydrastis canadensis are taken concurrently with common cancer treatments. Conversely, pharmacodynamic interactions between Hangeshashinto (TJ-14) and some cancer treatments have been shown to reduce the side effects of diarrhoea and oral mucositis. In summary, research in this area is limited and requires further investigation.

Citing Articles

Characterization and interactions between piperine and ezetimibe in their Anti-hyperlipidemic efficacy using Biopharmaceutics and Pharmacokinetics.

Marati K, Palatheeya S, Chettupalli A, Bukke S BMC Pharmacol Toxicol. 2025; 26(1):7.

PMID: 39810264 PMC: 11730522. DOI: 10.1186/s40360-025-00836-z.

Epimesatines P-S: Four Undescribed Flavonoids from Maxim. and Their Cytotoxicity Activities.

Xie S, Yu X, Zhang J, Hao Z, Zheng X, Feng W Molecules. 2024; 29(19).

PMID: 39407639 PMC: 11477557. DOI: 10.3390/molecules29194711.

Traditional and Complementary Medicine Use among Cancer Patients in Asian Countries: A Systematic Review and Meta-Analysis.

Choi S, Karki Kunwor S, Im H, Choi D, Hwang J, Ahmed M Cancers (Basel). 2024; 16(18).

PMID: 39335102 PMC: 11429845. DOI: 10.3390/cancers16183130.

Design, Synthesis, and Anticancer Activity of Novel Enmein-Type Diterpenoid Derivatives Targeting the PI3K/Akt/mTOR Signaling Pathway.

Wang J, Wang L, Zhang Y, Pan S, Lin Y, Wu J Molecules. 2024; 29(17).

PMID: 39274913 PMC: 11396751. DOI: 10.3390/molecules29174066.

Mistletoe Extract in Patients With Advanced Pancreatic Cancer: a Double-Blind, Randomized, Placebo-Controlled Tial (MISTRAL).

Wode K, Kienle G, Bjor O, Fransson P, Sharp L, Elander N Dtsch Arztebl Int. 2024; 121(11):347-354.

PMID: 38915151 PMC: 11539882. DOI: 10.3238/arztebl.m2024.0080.

References

Kappauf H, Bruntsch U, Horneber M, Kaiser G, Buschel G, Gallmeier W . Use of and attitudes held towards unconventional medicine by patients in a department of internal medicine/oncology and haematology. Support Care Cancer. 2000; 8(4):314-22. DOI: 10.1007/s005209900111. View

Oh B, Butow P, Mullan B, Beale P, Pavlakis N, Rosenthal D . The use and perceived benefits resulting from the use of complementary and alternative medicine by cancer patients in Australia. Asia Pac J Clin Oncol. 2010; 6(4):342-9. DOI: 10.1111/j.1743-7563.2010.01329.x. View

Hlubocky F, Ratain M, Wen M, Daugherty C . Complementary and alternative medicine among advanced cancer patients enrolled on phase I trials: a study of prognosis, quality of life, and preferences for decision making. J Clin Oncol. 2007; 25(5):548-54. DOI: 10.1200/JCO.2005.03.9800. View

Kumar N, Hopkins K, Allen K, Riccardi D, Besterman-Dahan K, Moyers S . Use of complementary/integrative nutritional therapies during cancer treatment: implications in clinical practice. Cancer Control. 2002; 9(3):236-43. DOI: 10.1177/107327480200900307. View

Cohen M, Hunter J . Complementary medicine products: interpreting the evidence base. Intern Med J. 2017; 47(9):992-998. DOI: 10.1111/imj.13534. View

Barnes J . Quality, efficacy and safety of complementary medicines: fashions, facts and the future. Part I. Regulation and quality. Br J Clin Pharmacol. 2003; 55(3):226-33. PMC: 1884210. DOI: 10.1046/j.1365-2125.2003.01810.x. View

Coxeter P, McLachlan A, Duke C, Roufogalis B . Herb-drug interactions: an evidence based approach. Curr Med Chem. 2004; 11(11):1513-25. DOI: 10.2174/0929867043365198. View

Niu J, Straubinger R, Mager D . Pharmacodynamic Drug-Drug Interactions. Clin Pharmacol Ther. 2019; 105(6):1395-1406. PMC: 6529235. DOI: 10.1002/cpt.1434. View

Ekhart C, Rodenhuis S, Smits P, Beijnen J, Huitema A . An overview of the relations between polymorphisms in drug metabolising enzymes and drug transporters and survival after cancer drug treatment. Cancer Treat Rev. 2008; 35(1):18-31. DOI: 10.1016/j.ctrv.2008.07.003. View

10.

Hartmann J, Haap M, Kopp H, Lipp H . Tyrosine kinase inhibitors - a review on pharmacology, metabolism and side effects. Curr Drug Metab. 2009; 10(5):470-81. DOI: 10.2174/138920009788897975. View

11.

Mizuno N, Niwa T, Yotsumoto Y, Sugiyama Y . Impact of drug transporter studies on drug discovery and development. Pharmacol Rev. 2003; 55(3):425-61. DOI: 10.1124/pr.55.3.1. View

12.

Lin J, Yamazaki M . Role of P-glycoprotein in pharmacokinetics: clinical implications. Clin Pharmacokinet. 2002; 42(1):59-98. DOI: 10.2165/00003088-200342010-00003. View

13.

Saneja A, Khare V, Alam N, Dubey R, Gupta P . Advances in P-glycoprotein-based approaches for delivering anticancer drugs: pharmacokinetic perspective and clinical relevance. Expert Opin Drug Deliv. 2013; 11(1):121-38. DOI: 10.1517/17425247.2014.865014. View

14.

Stieger B, Mahdi Z, Jager W . Intestinal and Hepatocellular Transporters: Therapeutic Effects and Drug Interactions of Herbal Supplements. Annu Rev Pharmacol Toxicol. 2016; 57:399-416. DOI: 10.1146/annurev-pharmtox-010716-105010. View

15.

Dolton M, Roufogalis B, McLachlan A . Fruit juices as perpetrators of drug interactions: the role of organic anion-transporting polypeptides. Clin Pharmacol Ther. 2012; 92(5):622-30. DOI: 10.1038/clpt.2012.159. View

16.

Chrubasik-Hausmann S, Vlachojannis J, McLachlan A . Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol. 2018; 71(1):129-138. DOI: 10.1111/jphp.12858. View

17.

Rodrigues A, Lai Y, Shen H, Varma M, Rowland A, Oswald S . Induction of Human Intestinal and Hepatic Organic Anion Transporting Polypeptides: Where Is the Evidence for Its Relevance in Drug-Drug Interactions?. Drug Metab Dispos. 2019; 48(3):205-216. DOI: 10.1124/dmd.119.089615. View

18.

Greenblatt D . Mechanisms and Consequences of Drug-Drug Interactions. Clin Pharmacol Drug Dev. 2017; 6(2):118-124. DOI: 10.1002/cpdd.339. View

19.

Nicolussi S, Drewe J, Butterweck V, Zu Schwabedissen H . Clinical relevance of St. John's wort drug interactions revisited. Br J Pharmacol. 2019; 177(6):1212-1226. PMC: 7056460. DOI: 10.1111/bph.14936. View

20.

Yang J, Kjellsson M, Rostami-Hodjegan A, Tucker G . The effects of dose staggering on metabolic drug-drug interactions. Eur J Pharm Sci. 2003; 20(2):223-32. DOI: 10.1016/s0928-0987(03)00200-8. View