Abstract
Breast cancer is a growing health issue globally and accounts as a second most cause of mortality. Natural products have been a fundamental of health care for long. Plants derived natural products have gained considerable attention over synthetic medicines, since they are safe and non-toxic. Krameria lappacea (Dombey) Burdet and B.B. Simpson plant belonging to Krameriaceae family, has been known for its beneficial effects against diseases. Herein, firstly, cytotoxic potential of petroleum ether (KLH), chloroform (KLC), ethyl acetate (KLEA), and ethanolic (KLET) extracts of K. lappacea was screened against MCF-7 cells exposed to 10-1000 μg/mL for 24 h. Secondly, the most cytotoxic extract (KLH) was used to explore the mechanisms of cytotoxicity in MCF-7 cells. MCF-7 cells were treated with KLH at 250-1000 μg/mL to measure the oxidative stress markers (glutathione (GSH) and lipid peroxidation (LPO)) and reactive oxygen species (ROS) generation. Further, loss of mitochondrial membrane potential (MMP) and caspase-3 and -9 enzyme activities were studied. The viability of MCF-7 cells were decreased from 44% to 90% for KLH, from 7% to 71% for KLEA, from 39% to 80% for KLC, and from 3% to 81% for KLET, respectively at 250-1000 μg/mL as observed by MTT assay. An increase of 91% in LPO and 2.2-fold in ROS generation and a decrease of 59% in GSH and 68% in MMP levels at 1000 μg/mL showed that KLH induced MCF-7 cell death via oxidative stress and elevated level of ROS generation which further leads to mitochondrial membrane dysfunction and activation of caspase enzymes. The findings of this study provide a mechanistic insight on anticancer efficacies of K. lappacea extracts against MCF-7 cells and support the use of it for the treatment of breast cancer diseases.