Andrographolide Selectively Inhibits the Growth of LA7 Mammary Adenocarcinoma Cells

Breast cancer (BC) causes significant mortality and morbidity, specifically in women globally. The first line of available therapies are far from satisfactory due to their adverse side effects, drug resistance, and reoccurrence of the cancer. As a result, natural source-based complementary medicines with anticancer activity and lesser side effects are widely investigated. Andrographolide (AGL), an active phytomolecule of <i>Andrographis paniculata</i>, exhibits diverse pharmacological activities against various diseases. The purpose of the study is to investigate the potential anticancer activity of AGL on LA7 cells, an <i>in vitro</i> mammary tumor model system, to understand its interaction with red blood cells (RBC) and effect on their membrane integrity. LA7 is a mammary adenocarcinoma cell line established by Renato Dulbecco in 1979 from the mammary tumor of Sprague-Dawley (SD) rat treated with 7,12-dimethylbenz-[<i>a</i>]-anthracene (DMBA). At first, a simple, rapid solvent extraction-gravimetric column chromatography method was employed for separation and purification of AGL from the dried leaf extract of <i>A. paniculata</i>. AGL showed significant anticancer activities on LA7 cells, with a potency similar to tamoxifen, an FDA-approved drug for BC. Mechanistic investigation showed that AGL triggers DNA damage, disruption of mitochondrial integrity, oxidative stress, cell cycle arrest at the G2/M phase, and apoptosis in LA7 mammary tumor cells. Furthermore, computational studies were performed to study the atomistic level understanding of AGL targeting LA7 cells. AGL exhibited a strong stable interaction with the active sites of BCL-2, NF-κB, and PKC-α proteins. Hematological complications are common side effects of most of the chemotherapeutic drugs. Toxicity analysis using Sprague-Dawley (SD) rats and human blood cells demonstrated no deleterious effects of AGL and devoid of hemolysis of RBCs. Morphological analysis by light and scanning electron microscopy (SEM) showed no observable changes in structural integrity of RBC membranes indicating nonhemolytic nature of AGL. Our results suggested that AGL has significant potential to be explored as an anticancer agent in BC therapy without any RBC toxicity.