Deoxyelephantopin and Its Isomer Isodeoxyelephantopin: Anti-Cancer Natural Products with Multiple Modes of Action

Abstract

Cancer is a leading cause of morbidity and mortality worldwide. The development of cancer involves aberrations in multiple pathways, representing promising targets for anti-cancer drug discovery. Natural products are regarded as a rich source for developing anti-cancer therapies due to their unique structures and favorable pharmacology and toxicology profiles. Deoxyelephantopin and isodeoxyelephantopin, sesquiterpene lactone compounds, are major components of Elephantopus scaber and Elephantopus carolinianus, which have long been used as traditional medicines to treat multiple ailments, including liver diseases, diabetes, bronchitis, fever, diarrhea, dysentery, cancer, renal disorders, and inflammation-associated diseases. Recently, deoxyelephantopin and isodeoxyelephantopin have been extensively explored for their anti-cancer activities. This review summarizes and discusses the anti-cancer activities of deoxyelephantopin and isodeoxyelephantopin, with an emphasis on their modes of action and molecular targets. Both compounds disrupt several processes involved in cancer progression by targeting multiple signaling pathways deregulated in cancers, including cell cycle and proliferation, cell survival, autophagy, and invasion pathways. Future directions of research on these two compounds towards anti-cancer drug development are discussed.

Chitosan Oligosaccharide Prevents Afatinib-Induced Barrier Disruption and Chloride Secretion through Modulation of AMPK, PI3K/AKT, and ERK Signaling in T84 Cells

“…MAPK-ERK regulates the cell cycle, gene expression, cell differentiation, cell survival, and apoptosis [ 45 ], whereas AMPK regulates cellular metabolism [ 46 ]. Several studies have shown that these two signaling cascades have intricate interplays in physiological and pathological processes [ 40 ].…”

Natural Products for Drug Discovery in the 21st Century: Innovations for Novel Therapeutics

“…Overall, the many exciting findings newly described [6][7][8][9][10][11][12][13] and reviewed [14][15][16][17] in this Special Issue can confidently lead us to a simple conclusion: natural products have a very bright future in the drug research of the 21st century!…”

“…A new approach to investigating the mechanism of action of bioactive NPs using atomic force microscopy described in the article by Knetzger et al also deserves special mention due to its high development potential [13]. The reviews within this SI [14][15][16][17], finally, provide a comprehensive source of current knowledge on particularly interesting types of NPs and their bioactivity. Indeed, the discovery of an entirely new mechanism of anticancer action with various NPs targeting it [17] demonstrates that NP research still yields fundamentally new findings in drug research based on the search for promising leads to develop innovative antitumor therapies.…”

“…Cancer certainly remains one of the most challenging health risks to humankind, and it is therefore no wonder that three out of the four reviews [15][16][17] focus entirely on NPs with anticancer activity and potential utility as leads against various neoplastic diseases. It is highly interesting and worth mentioning in this editorial that one particular class of NPs, sesquiterpene lactones (STLs), plays a major role in all three of these reviews.…”

“…Among the compounds mentioned in the review [15] is the STL deoxyelephantopin from the Elephatopus species (Asteraceae), which had previously been demonstrated to act against cancer cells. The promising antitumor potential of this compound and its congener isodeoxyelephantopin is the subject of the review by Mehmood and Muanprasad [16]. The authors provide a detailed overview on these compounds' multi-faceted interference with signaling pathways involved in cancer progression, ultimately leading to apoptosis.…”