Cancer: Leukemia
Action: Anti-oxidative, MDR
Leukemia
Because tumor necrosis factor-alpha (TNF-alpha) is well known to induce inflammatory responses, its clinical use is limited in cancer treatment. Rosmarinic acid (RA), a naturally occurring polyphenol flavonoid, has been reported to inhibit TNF-alpha-induced NF-kappaB activation in human dermal fibroblasts. Investigation found that RA treatment significantly sensitizes TNF-alpha-induced apoptosis in human leukemia U937 cells through the suppression of nuclear transcription factor-kappaB (NF-kappaB) and reactive oxygen species (ROS). This inhibition was correlated with suppression of NF-kappaB-dependent anti-apoptotic proteins (IAP-1, IAP-2, and XIAP). RA treatment also normalized TNF-alpha-induced ROS generation. Additionally, ectopic Bcl-2 expressing U937 reversed combined treatment-induced cell death, cytochrome c release into cytosol, and collapse of mitochondrial potential.
Results demonstrated that RA inhibits TNF-alpha-induced ROS generation and NF-kappaB activation, and enhances TNF-alpha-induced apoptosis (Moon, Kim, Lee, Choi, & Kim, 2010).
MDR
The intracellular accumulation of adriamycin, rhodamine123 (Rh123), and the expression of P-glycoprotein (P-gp) were assayed by flow cytometry. The influence of RA on the transcription of MDR1 gene was determined by reverse transcription-polymerase chain reaction. The results showed that RA could reverse the MDR of SGC7901/Adr cells, increase the intracellular accumulation of Adr and Rh123, and decrease the transcription of MDR1 gene and the expression of P-gp in SGC7901/Adr cells (Li et al., 2013).
Anti-cancer
Rosmarinic acid (RA), one of the major components of polyphenol, possesses attractive remedial features. Supplementation with RA significantly reduced the formation of aberrant crypt foci (ACF) and ACF multiplicity in 1,2-dimethylhydrazine (DMH) treated rats. Moreover RA supplementation prevented the alterations in circulatory anti-oxidant enzymes and colonic bacterial enzymes activities. Overall, results showed that all three doses of RA inhibited carcinogenesis, though the effect of the intermediary dose of 5 mg/kg b.w. was more pronounced (Karthikkumar et al., 2012).
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