Chemical evaluation and cytotoxic mechanism investigation of Clinacanthus nutans extract in lymphoma SUP-T1 cells.

ABSTRACT

Clinacanthus nutans has been used as herbal medicine with antidiabetic, blood pressure lowering, and diuretic properties in Singapore, Thailand, and Malaysia. The in vitro cellular study showed the chloroform extract possessed significant cytotoxicity against leukemia K562 and lymphoma Raji cells. The clinical study reported that administration of plant could treat or prevent relapse in 12 cancer patients. However, detailed mechanism of the anticancer effects and chemical profiles are not thoroughly studied. The chemical study did show that the acetone extract (MHA) exerted the highest antiproliferative effect on human leukemia MOLT-4 cells and lymphoma SUP-T1 cells in dose-dependent cytotoxicity. We found that the use of MHA increased apoptosis by 4.28%-43.65% and caused disruption of mitochondrial membrane potential (MMP) by 11.79%-26.93%, increased reactive oxygen species (ROS) by 19.54% and increased calcium ion by 233.83%, as demonstrated by annexin-V/PI, JC-1, H2 DCFDA, and Flou-3 staining assays, respectively. MHA-induced ER stress was confirmed by increase expression of CHOP and IRE-1α with western blotting assay. In conclusion, we identified good bioactivity in Clinacanthus nutans and recognize its potential effect on cancer therapy, but further research is needed to determine the use of the plant.