Abstract
For centuries, plants have been exploited by mankind as sources of numerous cancer chemotherapeutic agents. Good examples of anticancer compounds of clinical significance today include the taxanes (e.g., taxol), vincristine, vinblastine, and the podophyllotoxin analogues that all trace their origin to higher plants. While all these drugs, along with the various other available therapeutic options, brought some relief in cancer management, a real breakthrough or cure has not yet been achieved. This critical review is a reflection on the lessons learnt from decades of research on the iridoid glycoside geniposide and its aglycone, genipin, which are currently used as gold standard reference compounds in cancer studies. Their effects on tumour development (carcinogenesis), cancer cell survival, and death, with particular emphasis on their mechanisms of actions, are discussed. Particular attention is also given to mechanisms related to the dual pro-oxidant and antioxidant effects of these compounds, the mitochondrial mechanism of cancer cell killing through reactive oxygen species (ROS), including that generated through the uncoupling protein-2 (UCP-2), the inflammatory mechanism, and cell cycle regulation. The implications of various studies for the evaluation of glycosidic and aglycone forms of natural products in vitro and in vivo through pharmacokinetic scrutiny are also addressed.
Highlights
Plants have been extensively used by mankind to treat a number of diseases, including cancer
We have identified many other compounds that can induce pro-oxidative biological effects in the presence of copper ions, as well as cytotoxicity in cancer cells [159,160,161,162,163,164]
Through the effect related to Uncoupling Protein-2 (UCP2) inhibition, Mailloux et al [176] have shown that drug-resistant leukemic cells could be sensitized to the cytotoxic action of menadione, doxorubicin, and epirubicin when co-treated with genipin
Summary
Plants have been extensively used by mankind to treat a number of diseases, including cancer. Biomedicines 2018, 6, 39 and teniposide) that act by inhibiting topoisomerase II are further remarkable examples of anticancer drug discoveries based on natural products/plants Another group of plant-derived therapeutic agents are the cytotoxic quinoline alkaloids, such as camptothecin, which inhibit topoisomerase I. Whether one aims to discover novel drugs or validate those natural sources (e.g., plants) commonly used as traditional medicine in developing nations, scrutinizing decades of research on those reported to show some promise is a vital scientific endeavor. In this regard, the present review highlights the lessons learned from researches on the iridoid glycoside, geniposide, and its aglycone, genipin
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