A team led by Dr. Khosit Pinmai from Thammasat University has investigated the combination effects of P. emblica and T. bellerica extracts with conventional cytotoxic agents against human cancer cells. This study shows a synergistic effect of P. emblica and T. bellerica extracts with doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells.
Several herbs with diversified pharmacological properties are known to be rich sources of chemical constituents that may have potential for the treatment of several human cancers. Data from the Department of Preclinical Science, Faculty of Medicine, Thammasat University, demonstrates that the growth inhibitory activity of doxorubicin or cisplatin, as single agents, may be modified in combination with emblic myrobalan or belleric myrobalan extracts and may be synergistically enhanced in some cases.
An article to be published on March 14, 2008, in the World Journal of Gastroenterology demonstrates the combination of effective phytochemicals with chemotherapeutic agents. A study was conducted by Khosit Pinmai of Thammasat University, in which he evaluated the interaction of myrobalan extracts with chemotherapeutic drugs on cancer cell growth by isobologram and the combination index (CI) method of Chou-Talalay.
Several studies have shown that doxorubicin and cisplatin have harmful effects on health and can lead to the development of primary and secondary drug resistance in tumor cells, thereby limiting the clinical success of cancer chemotherapy. Recent reports show that combination chemotherapy is a superior modality and that naturally occurring dietary supplements with known anti-cancer properties could be used in combination chemotherapy to reduce the systemic toxicity of chemotherapeutic agents.
The study provides corroborative evidence, as it shows that emblic myrobalan and belleric myrobalan extracts were selectively toxic against two cancer cell lines and that in combination with doxorubicin and cisplatin produced an increased growth inhibitory effect in both hepatocellular carcinoma (HEpG2) and lung cancer (A549) cells. When using synergistic drug combinations at corresponding dose levels, the calculation of the dose reduction index (DRI) at the IC50 demonstrated possible reductions in doxorubicin concentrations for the drug combinations, ranging from 1.64-fold (myrobalan + doxorubicin in A549) to 4.69-fold (myrobalan + doxorubicin in HEpG2). The dose reduction level was different and specific to each combination and cell line.
These findings support the hypothesis that combinations of plant extracts and chemotherapeutic agents allow a reduction in the dosage of the latter (e.g., doxorubicin and cisplatin), while retaining the benefits but minimizing the cytotoxic effects, thus enhancing therapeutic efficacy.
In the view of the authors, the mechanism of interaction between myrobalan extracts and chemotherapeutic drugs is unclear, and it is possible that multiple compounds in the myrobalan extracts are involved. Previously, phytochemical studies have shown that myrobalan contains a variety of chemical components, including hydrolysable tannins (e.g., emblicanin, gallic acid and ellagic acid).
Further studies are needed to assess the underlying mechanism(s) and signal transduction pathways leading to growth inhibition induced by single agents and combinations both in vitro and in vivo.
Reference: Pinmai K, Chunlaratthanabhorn S, Ngamkitidechakul C, Soonthornchareon N, Hahnvajanawong C. Synergistic growth inhibitory effects of Phyllanthus emblica and Terminalia bellerica extracts with conventional cytotoxic agents doxorubicin and cisplatin against human hepatocellular carcinoma and lung cancer cells. World J Gastroenterol 2008; 14(10): 1491-1497
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