Interaction of a traditional Chinese Medicine (PHY906) and CPT-11 on the inflammatory process in the tumor microenvironment

Abstract

Background -Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906.Methods -Using a systems biology approach, we studied tumor tissue to identify reasons for the enhancement of the antitumor effect of CPT-11 (CPT-11) by PHY906 in a well-characterized pre-clinical model; the administration of PHY906 and CPT-11 to female BDF-1 mice bearing subcutaneous Colon 38 tumors.Results -We observed that 1) individually PHY906 and CPT-11 induce distinct alterations in tumor, liver and spleen; 2) PHY906 alone predominantly induces repression of transcription and immune-suppression in tumors; 3) these effects are reverted in the presence of CPT-11, with prevalent induction of pro-apoptotic and pro-inflammatory pathways that may favor tumor rejection.Conclusions -PHY906 together with CPT-11 triggers unique changes not activated by each one alone suggesting that the combination creates a unique tissue-specific response.

Old formula, new Rx: The journey of PHY906 as cancer adjuvant therapy

“…The results indicated that PHY906 could reduce inflammation when given alone. PHY906 was also able to enhance acute pro-inflammatory processes within the tumor when given in combination with CPT-11 (Wang et al, 2011). …”

Omic techniques in systems biology approaches to traditional Chinese medicine research: Present and future

“…Using a systemic approach, it applies a "top down" strategy to study the functions and perturbations of a biological system, from the end products of the metabolic network. This endows metabonomics with a holistic view, making it closer to TCM thinking and particularly fit to study pharmacological and toxicological effects of CHM (Lao et al, 2009;Wang et al, 2005Wang et al, , 2011aZhang et al, 2010). Used with a holistic approach, metabonomics has been also exploited to study and characterise Chinese medicine syndromes in several experimental models, recently reviewed (Wang et al, 2011a,b,c;Zhang et al, 2010).…”

Safety Surveillance of Traditional Chinese Medicine: Current and Future

“…Preclinical studies suggested PHY906 could enhance the therapeutic indices of a broad spectrum of anticancer agents without changing the pharmacokinetics of the chemotherapeutic agents studied. The mechanisms of action of PHY906 have been studied extensively [88, 89]. Various doses of PHY906 have been tested in phase I and II clinical trials in combination with escalating doses of irinotecan or capecitabine in a variety of solid tumors, and apecitabine for pancreatic and hepatocellular carcinomas.…”