Study of the cytotoxicity of asiaticoside on rats and tumour cells

Abstract

BackgroundCancer chemoprevention is considered one of the most promising areas in current cancer research, and asiaticoside, which is derived from the plant Centella asiatica, has a relative lack of systemic toxicity. The purpose of this study was to investigate whether asiaticoside is effective against 7,12-dimethylbenz(a)anthracene (DMBA)-induced carcinogenicity in vitro (MCF-7 and other cells) and in vivo (DMBA-induced rat cancer).MethodsAn MTT assay was performed involving the treatment of MCF-7 cells for 48 h with H2O2 alone and H2O2 + different asiaticoside concentrations. Flow cytometry was performed, and the level of caspase 3, tumour necrosis factor-alpha (TNF-α) and interleukin-1 (IL-1) were quantified. Adult female Sprague–Dawley (SD) rats were divided into five groups designated I (control), II (DMBA-induced cancer), III (pre- and post-treatment with asiaticoside (200 μg/animal) in DMBA-induced cancer), IV (post-treatment with asiaticoside in DMBA-induced cancer), and V (treated with asiaticoside alone, drug control). Twelve weeks post-DMBA, rats developed mammary tumours. Rats either were sacrificed or imaged with MIBI. Histological examination of tumour tissues was performed. Tumour MIBI uptake ratios were determined. The data are expressed as the means ± standard deviation. Appropriate t-test and ANOVA statistical methods were used to compare data.ResultsThe IC50 of asiaticoside for MCF-7 cells was determined to be 40 μM. Asiaticoside has potential for hydrogen peroxide cytotoxicity, and the caspase-3 activity increased with increasing asiaticoside dose in MCF-7 cells treated for 48 h. The expression of the cytokines TNF-α and IL-1β was significantly decreased and correlated with MIBI uptake ratios in vitro and in vivo after asiaticoside administration.ConclusionThis study demonstrates that asiaticoside is effective in vitro and in vivo in inducing apoptosis and enhancing anti-tumour activity.

RETRACTED: Dose‐dependent chemopreventive effects of citronellol in DMBA‐induced breast cancer among rats

“…The number of tumors per rat was calculated by physical examination of the mammary glands through touch and the palpable tumors were counted. The tumor volume and burden were calculated using V = 4/3π (D1/2) (D2/2) (D3/2) in which D1, D2, and D3 are three diameters (in mm) of the tumor (Al‐Saeedi, ).…”

In Silico Analyses and Cytotoxicity Study of Asiaticoside and Asiatic Acid from Malaysian Plant as Potential mTOR Inhibitors

“…Thus, asiaticoside from Centella asiatica was selected from the top 100 compounds because it has lower docking score and an equal/lower Lipinski rules violation than everolimus. Asiaticoside successfully showed its antitumor activity in vitro (KM3/BTZ multiple myeloma cell line and human breast cancer (MCF-7) cell line [ 39 , 40 ] and in vivo (7,12-Dimethylbenz(a)anthracene (DMBA)-induced rat mammary cancer) [ 40 ]. Despite the higher ∆G value of asiatic acid (−11.54 kcal/mol) compared to everolimus, it was selected as a potential mTOR inhibitor due to its well-proven antitumor activity against various other types of cancer, such as human ovarian cancer, hepatoma, colon cancer, and breast cancer [ 41 , 42 , 43 , 44 ].…”

“…Furthermore, natural products are more prone to resemble biosynthetic intermediates or endogenous metabolites than purely synthetic compounds and, thus, make use of active transport mechanisms [ 51 ]. Indeed, further justifications for selection of these compounds (asiaticoside and asiatic acid) as potential mTOR inhibitors are due to their relative lack of systemic toxicity [ 40 , 53 , 54 ], easily availability, and affordability.…”

Asiaticoside suppresses cell proliferation by inhibiting the NF‑κB signaling pathway in colorectal cancer

“…AC reduces the incidence of DMBA-induced breast cancer in rats by inhibiting expression of TNF-α and IL-1β ( 20 ). AC treatment considerably suppresses the proliferation of human breast cancer MCF-7 cells, and induces cell apoptosis in vitro ( 17 ).…”