Anti-cancer activity of asiatic acid against human cholangiocarcinoma cells through inhibition of proliferation and induction of apoptosis

Abstract

Plant-derived anti-cancer agents have been of considerable interest due to their promising effectiveness with low side effects. Asiatic acid, the main constituent of the medicinal plant Centella asiatica (L.) Urban, has a wide range of biological properties such as antioxidant, anti-inflammatory and anti-cancer activities. Cholangiocarcinoma (CCA), which is a malignant tumor of bile duct epithelium, is one of the leading cancers in Southeast Asia, notably the northeast of Thailand where the liver fluke, Opisthorchis viverrini predominates. Many in vitro and in vivo studies have provided evidence supporting that oxidative stress induced by chronic inflammation is involved in CCA genesis with aggressive clinical outcomes. This study was performed to evaluate the cytotoxic effects of asiatic acid on two human CCA cell lines (KKU-156 and KKU-213). Cell viability was determined by a sulforhodamine B (SRB) assay. Morphological changes of the cells were observed by microscopy. Cell apoptosis was detected by flow cytometry using annexin V and propidium iodide (PI) staining. Messenger RNA (mRNA) expression levels of BAX, BCL2 and Survivin/BIRC5 were analyzed by real-time polymerase chain reaction (PCR). It was found that asiatic acid efficiently suppressed CCA cellular viability via induction of apoptosis. In addition, the occurrence of asiatic acid-induced apoptosis was confirmed by microscopic observation of apoptotic vesicles, down-regulation of anti-apoptotic genes (BCL2 and Survivin/BIRC5) and increased early and late apoptotic cells. Our results showed the chemotherapeutic activities of asiatic acid, suggesting the anti-cancer properties of this compound should be clinically assessed and its supplementation may lead to an improvement of survival of CCA patients.

Asiatic Acid, Extracted from Centella asiatica and Induces Apoptosis Pathway through the Phosphorylation p38 Mitogen-Activated Protein Kinase in Cisplatin-Resistant Nasopharyngeal Carcinoma Cells

“…It has been proposed that Asiatic acid has various pharmacological activities such as anti-inflammatory and antioxidant, as well as the potent anti-hypertensive, neuro and cardio-protective, antimicrobial, and antitumor activities [5]. Many studies had proved the anti-cancer effects in vitro or in vivo of AA in breast cancer, ovary cancer, colon cancer, gastric cancer, cholangiocarcinoma, glioblastoma, lung cancer, lymphoma, and melanoma [6,[11][12][13][14][15][16][17][18]. Our study corresponds with these researches and revealed the anti-cancer effect of AA in both dose and time dependent manners in cisplatin-resistance NPC cell lines (Figure 1b).…”

Asiaticoside Antagonizes Proliferation and Chemotherapeutic Drug Resistance in Hepatocellular Carcinoma (HCC) Cells

“…For example, asiatic acid has shown anti-cancer effects in non-small cell lung cancer (NSCLC) by impeding transforming growth factor-β1 (TGF-β1)-induced epithelial-mesenchymal transition (EMT) [ 31 ]. In addition, asiatic acid also inhibits the proliferation of human cholangiocarcinoma cells through inhibition of proliferation and induction of apoptosis [ 32 ]. As a major compound of Centella asiatica , asiaticoside has been reported to show significant antitumor effects in multiple myeloma via mechanisms of action related to autophagy induction, activation of effector caspases, and inhibition of cell migration, invasion, and STAT-3 signaling pathways [ 17 ].…”

The The Effects of Centella asiatica Extract (CAE) on Methamphetamine-Induced Neurotoxicity via Human Neuroblastoma Cell Line

“…This cytotoxicity is due to asiatic acid found in CAE which induced apoptosis and cell death (Park et al, 2005). Sakonsinsiri et al (2018) also reported antitumor and cytotoxicity of CAE attributed by its high alkaloidal content.…”