Influence of Asiatic acid on cell proliferation and DNA damage in vitro and in vivo systems

Abstract

Asiatic acid (AA) is a triterpene with promising pharmacological activity. In the present study, in vitro and in vivo assays were conducted to understand the effect of AA on cell proliferation and genomic instability. AA was cytotoxic to human tumor cell lines (M059J, HeLa, and MCF‐7), with IC50 values ranging from 13.91 to 111.72 µM. In the case of M059J, AA exhibited selective cytotoxicity after 48 h of treatment (IC50 = 24 µM), decreasing the percentage of cells in the G0/G1 phase, increasing the percentage of cells in the S phase, and inducing apoptosis. A significant increase in chromosomal damage was observed in V79 cell cultures treated with AA (40 µM), revealing genotoxic activity. In contrast, low concentrations (5, 10, and 20 µM) of AA significantly reduced the frequencies of micronuclei induced by the mutagens doxorubicin (DXR), methyl methanesulfonate, and hydrogen peroxide. A reduction of DXR‐induced intracellular free radicals was found in V79 cells treated with AA (10 µM). The antigenotoxic effect of AA (30 mg/kg) was also observed against DXR‐induced chromosomal damage in Swiss mice. Significant reductions in p53 levels were verified in the liver tissue of these animals. Taken together, the data indicate that AA exerted antiproliferative activity in M059J tumor cells, which is probably related to the induction of DNA damage, leading to cell cycle arrest and apoptosis. Additionally, low concentrations of AA exhibited antigenotoxic effects and its antioxidant activity may be responsible, at least in part, for chemoprevention.

An Approach for Developing a Simple and Quick Method for Separation of Asiatic Acid and Asiaticoside Rich Fraction From Centella Asiatica and Simultaneous Determination by Reversed-Phase High-Performance Liquid Chromatography

“…Asiaticoside, madecassoside, and their sapogenin triterpene acids such as asiatic acid and madecassic acid are the most noticeable triterpenes present in C. asiatica. (Idris et al, 2021;Lu et al, 2021;Nouri et al, 2021;Ribeiro et al, 2021;Songvut et al, 2021;Sabaragamuwa et al, 2022) Polypharmacological properties of asiatic acid and asiaticoside sparked interest in the research community. Numerous researchers throughout the globe reported the different pharmacological properties of the active phytoconstituents such as anti-inflammatory, antioxidant, hepatoprotective properties, anti-diabetic properties, analgesic, antibacterial, cytotoxic, etc.…”

“…Numerous researchers throughout the globe reported the different pharmacological properties of the active phytoconstituents such as anti-inflammatory, antioxidant, hepatoprotective properties, anti-diabetic properties, analgesic, antibacterial, cytotoxic, etc. (Lu et al, 2021;Pingyod et al, 2021;Ribeiro et al, 2021;Thong et al, 2021;Mohammed et al, 2022). These pharmacological activities associated with the asiatic acid and asiaticoside has been thoroughly studied and well documented.…”

Asiatic acid inhibits osteosarcoma cell migration and invasion via the AKT/Sp1/MMP1 axis

“…[7][8][9] and has attracted recent attention regarding its diverse pharmacological properties including anti-inflammatory activity, 10 the promotion of wound healing, 11 neuroprotection, 12 and anti-cancer activity. 7,13,14 Studies have reported anti-cancer activities of AA that include inducing cell apoptosis by inhibiting cancer cell proliferation, 15 increasing endoplasmic reticulum (ER) stress, 16 and increasing reactive oxygen species (ROS) production. 17 Furthermore, AA demonstrates significant potential in impeding cancer cell metastasis by suppressing their migration and invasion capabilities and decreasing angiogenesis.…”