Natural Terpenoids Against Female Breast Cancer: A 5-year Recent Research

What is it about?

The approval of Taxol® in 1993 marked the great entrance of terpenoids in the anti-cancer area. Over decades, other prominent natural terpenoids have become indispensable for the modern pharmacotherapy of breast cancer. Given the rapid evolution of drug resistance, effective treatments for advanced breast cancers requiring cytotoxic chemotherapy represent a major unmet clinical need. Therefore, innovative agents effective in long-term chemotherapy are urgently needed. This review examines recent (January 1st, 2012 to December 31st, 2016) advances/research about natural terpenoids, and their mechanisms against female breast cancer.

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Why is it important?

Phytochemicals such as thymoquinone (8), costunolide (46), tanshinone IIA (132), triptolide (136), cucurbitacin B (179), celastrol (226) and lycopene (238) that simultaneously inhibited several or all aspects/steps (proliferation, migration, apoptosis resistance, tumor angiogenesis or metastasis) of cancer progression in vitro and in vivo appear to be promising to overcome breast cancer treatment failure and had caught our attention. Several chemicals are declared promising based only on their cytotoxicity/antiproliferative activities. This conclusion is often too limited and overestimated because they were tested in no or not more than two normal cell lines. Cytotoxicity and high selectivity (low cytotoxicity in normal cells) have to go together. Till today there is no concensus on the minimal number/type of normal cells to be used in a study and we suggested that at least normal cells from the organs/tissues such as liver, kidney, heart, bladder, neurons, and blood, the injury of which is associated with life-threating conditions have to be screened. Another weakness of the majority (up to 59%) of articles recorded is the lack of a positive control or standard/reference although many of these articles were published in highly-reputated, peer-reviewed international journals supposed to be rigorous and demanding. Positive control is indispensable and a part of good experimental design or properly performed studies in pharmacology. It helps to classify unexpected results and to determine the therapeutic and/or toxic effects of the investigated substance/chemical in correlation to the reference. Moreover, it is almost impossible to compare studies that lack positive controls or references. In line with this conflicting or quite different results (IC50 values) have been observed with many compounds. Such discrepancies are probably attributed to the (type of) assays used, the purity of compounds, the experimental set-up, operator’s experience or other experimental parameters including cell number, number of mitochondria and metabolic rate. To limit speculation on differing IC50 values, a combination of different types of assays (metabolic and non-metabolic) is recommended. Editors additionally have to put emphasis on the declaration of the purity of the investigated substance and that depending on the type of assay at least one suitable positive control has to be used.