Anticancer Activity of Aqueous Extracts of Terminalia arjuna ( TA ) Bark

Our previous study demonstrated that an aqueous extract of TA bark ( TA AqE ) exerts cardioprotection against toxicity induced by doxorubicin (DOX), a commonly‐used anticancer chemotherapeutic agent. However, whether TA AqE has any effect on cancer cells remains unknown. Herein we investigated the effects of TA AqE on several human lung and breast cancer cell lines (ATCC) in vitro and on mice (Wnt‐transgenic model) bearing mammary tumors. Cell morphology and growth were monitored with phase‐contrast microscopy, while the colorimetric Cell Counting Kit (CCK)‐8 assay was used to evaluate cell viability. Fluorescent microscopy with Hoechst H33342, AnnexinV, propidium iodide (PI), and JC‐1 (a mitochondrial membrane potential dye) was used to detect cell membrane and mitochondrial integrity. Tumor growth in vivo was monitored with ultrasound biomicroscopy. We found that TA AqE , its fractions (designated as P faction and S fraction) and the ethanol extract of TA bark ( TA EtOH ) at 50 μg/ml inhibited growth of all cancer cells with negligible effect on non‐tumor lung fibroblasts (CCD‐19Lu) after 24‐h treatment. The order of the cytotoxic potency (at 50 μg/ml) was TA EtOH > P fraction > TA AqE ~ S fraction > gallic acid (10 μM), an active component of TA AqE , based on the cell viability assay. When TA AqE was separated with Microcon filter devices, the molecular mass of active components was greater than 10 kDa. Distinct AnnexinV/PI expression of these cancer cells suggested differential effects of TA AqE on apoptotic status. TA AqE and TA EtOH caused dose‐dependent cytotoxicity of human lung adenocarcinoma cells (A549) with 50 μg/ml showing more effective effects and different morphological changes such as increasing cytosolic vacuolization compared to DOX (1 μM). In non‐small cell lung cancer cells (H1975), TA AqE (5 μg/ml) caused a decrease in mitochondrial membrane potential in contrast to CCD‐19LU cells. In vivo treatment of Wnt‐transgenic mice with TA AqE (15 mg/kg body weight, daily in drinking water) for 3 days or 4 weeks reduced mammary tumor sizes with no recurrence noted 3.5 weeks and one month post‐treatment, respectively. In conclusion, TA AqE displays potential as an adjunct for cancer therapy in addition to its cardiotoxic protective effects. Mechanistically, TA AqE may induce cell membrane damage and reduction of mitochondrial function of cancer cells. Support or Funding Information UAMS Seeds of Science Funds to SJL This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .