Abstract
Prostate cancer (PCa) is the most common diagnosed cancer and is the third cause of cancer mortality in men in the USA. Andrographolide, a diterpenoid lactone isolated from Andrographis paniculata, has shown to possess anticarcinogenic activity in a variety of cancer cells. In this study, we examined the efficacy of Andrographolide in PCa using in vitro and in vivo models. Androgen-independent (PC3) and androgen-dependent (22RV1) cell lines were treated with Andrographolide to determine the effect in cell motility, cell proliferation and apoptosis. Andrographolide decreased PCa cell migration, decreased invasion, and increased cell apoptosis in vitro. Tumor growth was evaluated using an orthotopic xenograft model in which the prostates of SCID mice were injected with 22RV1, and mice were treated three times per week with Andrographolide 10 mg/kg. Andrographolide decreased tumor volume, MMP11 expression and blood vessels formation in vivo. Gene expression analysis identified cellular compromise, cell cycle, and “DNA recombination, replication and repair” as the major molecular and cellular functions altered in tumors treated with Andrographolide. Within DNA repair genes we confirmed increased expression of genes involved in DNA double strand break repair. Consistent with this observation we detected increased γH2AX in Andrographolide treated tumors and in cells in culture. Taken together, these data suggest that Andrographolide inhibits PCa by promoting DNA damage.
Highlights
Prostate cancer (PCa) is the second most frequently diagnosed cancer in men, with 1.1 million new cases estimated in 2012 and was the fifth leading cause of cancer death in men worldwide in 2012 [1]
At 12 and 24 hours, the migration of PC3 cells was significantly reduced by 10% and 15%, respectively, in cells treated with Andrographolide (25 μM) when compared to control (P < 0.05) (Figure 2B)
It has been observed that Andrographolide inhibits cancer cell proliferation, induces cell-cycle arrest, and promotes apoptosis [18, 25, 26]
Summary
Prostate cancer (PCa) is the second most frequently diagnosed cancer in men, with 1.1 million new cases estimated in 2012 and was the fifth leading cause of cancer death in men worldwide in 2012 [1]. PCa is the most common cancer in men as well as one of the leading causes of cancer-related mortality in the United States [2]. Chemoprevention and prevention with phytochemicals has been widely studied in cancers such as lung, colon, breast and prostate cancer. The major component of this plant, Andrographolide, has www.oncotarget.com been reported to have therapeutic potential against liver disorders, common cough and cold, infection, inflammation and cancer in humans [7, 8, 10,11,12,13,14,15]. Previous studies demonstrate that Andrographolide possesses potent antiangiogenic activity and, since angiogenesis plays an important role in tumorigenesis, it could have potential therapeutic effects [19, 20]
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