Antitumor Efficacy of the Herbal Recipe Benja Amarit against Highly Invasive Cholangiocarcinoma by Inducing Apoptosis both In Vitro and In Vivo

Abstract

Thailand is the country with highest incidence and prevalence of cholangiocarcinoma (CCA) in the world. Due to the frequently late diagnosis that is associated with this disease, most CCA patients are prescribed chemotherapy as a form of treatment. However, CCA is able to resist the presently available chemotherapy, so to the prognosis of this disease is still very poor. In this study, we investigated the anticancer potential of a Thai herbal recipe, Benja Amarit (BJA) against CCA and the relevant mechanisms of action that are involved. We found that BJA inhibited CCA cell viability in a dose-dependent manner, especially in highly invasive KKU-213 cells. The extract induced mitochondrial- and caspase-dependent apoptosis in CCA cells by regulating the nuclear factor-κB (NF-κB) signaling pathway. BJA also triggered autophagy in CCA cells. Nonetheless, the inhibition of autophagy enhanced BJA-induced CCA cell death via apoptosis. An in vivo xenograft model revealed the growth-inhibiting and death-inducing effects of BJA against CCA by targeting apoptosis. However, general toxicity to blood cells, kidneys and the liver, as well as changes in body weight, did not appear. Our findings suggest that the herbal recipe BJA might be used as a potentially new and effective treatment for cholangiocarcinoma patients.

Effect of Calomelanone, a Dihydrochalcone Analogue, on Human Cancer Apoptosis/Regulated Cell Death in an In Vitro Model

“…The activation of autophagy depends on the duration of treatment. Autophagy is induced over a short period of treatment time, whereas apoptosis is activated over a longer period of treatment time [ 35 ]. Since calomelanone increased HepG2 cell viability at 24 h, the investigation of whether calomelanone induced HepG2 cell survival via the autophagy-mediated mechanism was performed by HepG2 cell treatment at various concentrations of IC values over 48 h but over a shorter incubation period (24 h).…”

“…At 24 h, the IC values could not be determined due to the proliferation character of HepG2 cells in response to calomelanone. Monodansylcadaverine (MDC) is a specific fluorescence dye for autophagosomes, autophagolysosomes, or autophagic vacuoles, representing the functional autophagic flux [ 35 , 36 ]. Stained cells, both cell morphology (qualitatively) and quantitatively positive stained cells, were examined under fluorescence microscopy and by flow cytometry, respectively.…”

“…Activation of autophagy depends on the concentration used and the duration of treatment time [ 35 ]. Furthermore, a high dose of levofloxacononone, a chalcone derivative, can inhibit autophagy and induce apoptosis of human hepatocellular carcinoma SMMC-7721 cells, whereas the cells are protected by autophagy at low concentrations [ 62 ].…”

Metal‐Organic Frameworks Deliver a Conjugate of Functional Oligonucleotides and Photosensitizer to Induce Apoptosis for Enhancing Chemotherapy

“…Apoptosis, formerly also called programmed cell death (PCD), [15] has been widely proved to be a major type of cell death to suppress cancer development. Therefore, induction of apoptosis is considered to be a potential antitumor strategy [16] . Overexpression of Bcl‐2 has been identified in numerous cancers [17] .…”

Plant-Based Bioactive Molecules in Improving Health and Preventing Lifestyle Diseases

“…In particular, Costantini et al showed that the hydroxytyrosol contained in olive oil ( Olea europea ) induces the apoptotic death of melanoma cells by increasing ROS levels, p53 and γH2AX expression and by the decrease in AKT expression [ 3 ]. A Thai herbal preparation known as Benja Amarit is capable of inducing apoptotic death in cholangiocarcinoma cells, through the regulation of the nuclear factor-KB (NF-KB) signaling pathway [ 4 ]. Both hydroxytyrosol and Benja Amarit preparation result in safe and promising therapeutic tools for the treatment of these highly invasive tumors.…”