Herb–Drug Interactions in Oncology: Focus on Mechanisms of Induction

Abstract

An increasing number of cancer patients are using complementary and alternative medicines (CAM) in combination with their conventional chemotherapeutic treatment. Considering the narrow therapeutic window of oncolytic drugs, this CAM use increases the risk of clinically relevant herb-anticancer drug interactions. Such a relevant interaction is that of St. John's wort with the anticancer drugs irinotecan and imatinib. It is, however, estimated that CAM-anticancer drug interactions are responsible for substantially more unexpected toxicities of chemotherapeutic drugs and possible undertreatment seen in cancer patients.Induction of drug-metabolizing enzymes and ATP-binding cassette drug transporters can be one of the mechanisms behind CAM-anticancer drug interactions. Induction will often lead to therapeutic failure because of lower plasma levels of the anticancer drugs, and will easily go unrecognized in cancer treatment, where therapeutic failure is common.Recently identified nuclear receptors, such as the pregnane X receptor, the constitutive androstane receptor, and the vitamin D-binding receptor, play an important role in the induction of metabolizing enzymes and drug transporters. This knowledge has already been an aid in the identification of some CAM probably capable of causing interactions with anticancer drugs: kavakava, vitamin E, quercetin, ginseng, garlic, β-carotene, and echinacea. Evidently, more research is necessary to prevent therapeutic failure and toxicity in cancer patients and to establish guidelines for CAM use. The Oncologist 2006;11:742-752 Learning ObjectivesAfter completing this course, the reader will be able to:1. Describe the possible pharmacokinetic interactions between complementary alternative medicines and oncolytic drugs and the clinical consequences thereof.2. Define the role of the nuclear receptors PXR, CAR, and VDR in herb-drug interactions.3. Discuss methods to measure induction of drug-metabolizing enzymes and transporters.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit

Phytochemicals: Extraction Methods, Basic Structures and Mode of Action as Potential Chemotherapeutic Agents

“…Molecular mechanisms of herb-drug interaction occur, the most notable is the ATP-binding cassette drug transporters such as P-glycoprotein (You & Moris, 2007) and the drug metabolizing enzymes (known as phase I and phase II enzymes), especially cytochrome P450 3A4 (CYP3A4) (Pal & Mitra, 2006;Meijerman et al, 2006).…”

Toxicity of Kava Kava

“…Since human CYP3A4 is responsible for approximately 60% of CYP450-mediated metabolism of drugs in therapeutic use today, with anti-cancer drugs in particular (69,70), this result suggests that kava can potentially affect drug metabolism. Upon metabolism, the kava lactones containing methylenedioxyphenyl group in kava extract inhibited multiple cytochrome P450 enzymes (71)(72)(73)(74)(75).…”

Protection by Panax ginseng C.A. Meyer against the genotoxicity of doxorubicin in somatic cells of Drosophila melanogaster

“…Plant products are being increasingly used as complementary or alternative medicines for the treatment for a variety of diseases, including cancer (Meijerman et al, 2006), although in many cases there is still only limited scientific evidence for their therapeutic efficacy. The root of Panax ginseng C. A. Meyer (Araliaceae), a common plant in eastern Asia, is widely used in Chinese natural medicine (Lee et al, 2004;Yoshikawa et al, 2007).…”

“…Because the use of alternative medicines in combination with conventional therapy may increase the risk of unwanted interactions in cancer patients (Meijerman et al, 2006), in this work we used the wing SMART to investigate the possible genotoxicity of three doses of a water-soluble form of the dry root of P. ginseng and its ability to protect against the genotoxicity of DOX. To our knowledge the effects of ginseng on DOX genotoxicity have not yet been studied in vitro or in vivo.…”