Cucurbitacin: Ancient Compound Shedding New Light on Cancer Treatment

Abstract

Cucurbitacins and their derivatives are triterpenoids found in medicinal plants known for their diverse pharmacological and biological activities, including anticancer effects, throughout human history. Although initial attention to cucurbitacin as a potential anticancer drug withered for decades, recent discoveries showing that cucurbitacin is a strong STAT3 (Signal Transducers and Activators of Transcription-3) inhibitor have reclaimed the attention of the drug industry one more time. There is increasing evidence showing that some cucurbitacins not only inhibit the JAK-STAT pathway, but also affect other signaling pathways, such as the MAPK pathway, which are also known to be important for cancer cell proliferation and survival. Moreover, some reports have shown the synergistic effect of cucurbitacins with known chemotherapeutic agents, such as doxorubicin and gemcitabine. In this review, we will summarize the recent discoveries regarding molecular mechanisms of action of cucurbitacins in human cancer cells and discuss the possibilities of cucurbitacin as a future anticancer drug in clinical settings.

Cucurbitacin I inhibits tumorigenic ability and enhances radiochemosensitivity in nonsmall cell lung cancer‐derived CD133‐positive cells

“…32 Several reports have indicated the synergistic effect of cucurbitacin with known chemotherapeutic agents, such as doxorubicin and gemcitabine. 33 In the current study, our data revealed that treatment with cucurbitacin I in CD133-positive NSCLC cells effectively improved their chemoresistance to cisplatin, doxorubicin, 5-FU, and paclitaxel (Fig. 5).…”

Focus on ADF/Cofilin: Beyond Actin Cytoskeletal Regulation

“…The actin cytoskeletal reorganization is involved in these phenotypes, and several toxins targeting on the networks of actin filaments have been reported to efficiently inhibit cell cycle progression and induce apoptosis in cancer cells [74,75]. For instance, cucurbitacins [76,77] derived from medicinal plants have many isoforms and they are widely used in cancer therapy because they disrupt the formation of filamentous actin and subsequently cause G2/M phase arrest and apoptosis in breast cancers [78], glioblastoma (GBM) [79], and prostate cancer [80]. In addition, a series of actin toxins that display highly antitumor effects have been used for anticancer researches by interfering the actin polymerization and depolymerization.…”

Study of chemical residues from Nemarioc-AL and Nemafric-BL phytonematicides in tomato fruit

“…However, at high concentrations, where growth of cells is inhibited, the cucurbitacins would be cytotoxic (Lee et al, 2010). The observation in this study, where cucurbitacins were undetectable (Figures 2 and 3), is important for the potential commercialisation of Nemarioc-AL and Nemafric-BL phytonematicides.…”

“…In density-dependent growth (DDG) context , the accumulation of cucurbitacin in edible produce and in subsequent products would be risky since in small quantities that characterise chemical residues, cucurbitacins could stimulate cell division in animals, thereby inducing cancer (Lee et al, 2010). However, at high concentrations, where growth of cells is inhibited, the cucurbitacins would be cytotoxic (Lee et al, 2010).…”