Abstract
Cancer cells are reported to have elevated levels of reactive oxygen species (ROS) and are highly dependent on cellular defense mechanisms against oxidative stress. Numerous nutraceuticals and natural polyphenolic compounds have a wide range of abilities to alter cellular redox states with potential implications in various diseases. Furthermore, therapeutic options for cancers are mostly nonselective treatments including genotoxic or tubulin-targeting compounds. Some of the natural extracts, containing multiple bioactive compounds, could target multiple pathways in cancer cells to selectively induce cell death. Cymbopogon citratus (lemongrass) and Camellia sinensis (white tea) extracts have been shown to have medicinal properties, however, their activity against lymphoma and leukemia, as well as mechanistic details, have not been fully characterized. Herein, we report potent anti-cancer properties in dose and time-dependent manners of ethanolic lemongrass and hot water white tea extracts in lymphoma and leukemia models. Both extracts were able to effectively induce apoptosis selectively in these human cancer cell types. Interestingly, ethanolic lemongrass extract induces apoptosis primarily by the extrinsic pathway and was found to be dependent on the generation of ROS. Conversely, apoptotic induction by hot water white tea extract was independent of ROS. Furthermore, both of these extracts caused mitochondrial depolarization and decreased rates of oxygen consumption in lymphoma and leukemia cells, leading to cell death. Most importantly, both these extracts were effective in reducing tumor growth in human lymphoma xenograft models when administered orally. Thus, these natural extracts could have potential for being nontoxic alternatives for the treatment of cancer.
Highlights
Conventional chemotherapeutics for the treatment of cancer lead to serious side effects due to the nonselective nature of these treatments, targeting features common to both healthy and cancerous cells
These results are complemented by the reduction in cleavage of caspase-8 and -9 by N-acetyl cysteine (NAC) co-treatment (Figure 5E). These results indicate that lemongrass and white extracts induce cell death by different mechanistic pathways; lemongrass extract appears to be dependent on oxidative stress for the induction of apoptosis whereas white tea extract is independent of oxidative stress
We have shown for the first time that lemongrass and white tea extracts exhibit different mechanisms of action for the induction of apoptosis in human lymphoma and leukemia cell lines in vitro and are effective in reducing tumor growth in vivo (Figures 2A, 5A, 7A)
Summary
Conventional chemotherapeutics for the treatment of cancer lead to serious side effects due to the nonselective nature of these treatments, targeting features common to both healthy and cancerous cells. The oxidative and mitochondrial vulnerabilities unique to cancer cells, such as their increased dependence on aerobic glycolysis (Warburg effect), can be exploited. Cancerous cells may use a differential pathway of metabolism; it has been reported that they generate higher amounts of reactive oxygen species www.impactjournals.com/oncotarget (ROS). They have unregulated anti-oxidative defense mechanisms, and an increase in the production of ROS can trigger apoptosis [1, 2, 3]. Cancerous mitochondria have been shown to be selectively susceptible to certain compounds, further indicating that there are vulnerabilities unique to cancer cells [4, 5]
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