Andrographolide induces DNA damage in prostate cancer cells

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.

Advances in ameliorating inflammatory diseases and cancers by andrographolide: Pharmacokinetics, pharmacodynamics, and perspective

“…Further study confirmed that andrographolide ameliorated prostate cancer by enhancing DNA damage. 239 This was consistent with Mir et al's research finding andrographolide reduced prostate cancer cell growth by targeting cell cycle regulators. 240 They have shown that andrographolide reduced prostate cancer cell migration by altering CXCL11, CXCR3, and CXCR7.…”

Andrographis paniculata and Its Bioactive Diterpenoids Protect Dermal Fibroblasts against Inflammation and Oxidative Stress

“…In 2014, Sareer et al showed that Andrographolide (ANDRO) is the main bioactive compound in the leaves of Andrographis paniculata [39]. To date, this molecule is known for its antiviral [40], anticancer [41], hepatoprotective [42], antioxidant [43] and anti-inflammatory [44] properties. Other diterpenoids are present in the aerial part of the plant: 14-deoxyandrographolide (14DAP) and 14-deoxy-11,12-didehydroandrographolide (14DAP11-12), neoandrographolide (NEO) (Figure 1).…”

Cytotoxicity and Synergistic Effect of Biogenically Synthesized Ternary Therapeutic Nano Conjugates Comprising Plant Active Principle, Silver and Anticancer Drug on MDA-MB-453 Breast Cancer Cell Line

“…Participation of unsaturated lactone present in AP could have played a role in stabilization and synergy by sensitization of cancer cells as reported in literature (Zhou et al, 2008, Zhou et al, 2010. The higher rate of cancer cell inhibition of the ternary combination involving AP could be arising through nuclear condensation derived induction of apoptosis and cell cycle arrest observed in several cancers (Venkatadri et al, 2016, Babykutty et al, 2008Forestier-Román et al, 2019). The cytotoxicity result shows that ternary formulation has greater advantage when it comes to inhibiting cancer cell line.…”