Andrographolide sensitizes prostate cancer cells to TRAIL-induced apoptosis

Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising agent for anticancer therapy. The identification of small molecules that can establish the sensitivity of prostate cancer (PCa) cells to TRAIL-induced apoptosis is crucial for the targeted treatment of PCa. PC3, DU145, JAC-1, TsuPr1, and LNCaP cells were treated with Andrographolide (Andro) and TRAIL, and the apoptosis was measured using the Annexin V/PI double staining method. Real time-polymerase chain reaction (PCR) and Western blot analysis were performed to measure the expression levels of target molecules. RNA interference technique was used to down-regulate the expression of the target protein. We established a nude mouse xenograft model of PCa, which was used to measure the caspase-3 activity in the tumor cells using flow cytometry. In this research study, our results demonstrated that Andro preferentially increased the sensitivity of PCa cells to TRAIL-induced apoptosis at subtoxic concentrations, and the regulation mechanism was related to the up-regulation of DR4. In addition, it also increased the p53 expression and led to the generation of reactive oxygen species (ROS) in the cells. Further research revealed that the DR4 inhibition, p53 expression, and ROS generation can significantly reduce the apoptosis induced by the combination of TRAIL and Andro in PCa cells. In conclusion, Andro increases the sensitivity of PCa cells to TRAIL-induced apoptosis through the generation of ROS and up-regulation of p53 and then promotes PCa cell apoptosis associated with the activation of DR4.

The Prowess of Andrographolide as a Natural Weapon in the War against Cancer

“…Similar mechanism has been reported in prostate cancer cells. TRAIL and andrographolide combinatorially induced regression of tumors in mice xenografted with prostate cancer cells [ 54 ]. Andrographolide effectively reduced NF-ҡB/p65 subunit and stimulated the expression of DR4 and DR5 in bladder cancer cells [ 55 ].…”

Enhanced anti-cancer activity of andrographis with oligomeric proanthocyanidins through activation of metabolic and ferroptosis pathways in colorectal cancer

“…Accumulating evidence has demonstrated additional effects of andrographis with some of the conventional chemotherapeutic drugs. For instance, andrographis potentiated the antitumor effects of topotecan, paclitaxel, cisplatin and gemcitabine in acute myeloid leukemia, non-small cell lung cancer, oral squamous cell carcinoma and pancreatic cancer, respectively [33][34][35][36] . Previous studies have also demonstrated the anti-proliferative and chemo-sensitizing properties of andrographis in CRC cells 37,38 .…”

Synthesis, extracorporeal nephrotoxicity, and 3D‐QSAR of andrographolide derivatives

“…F.) Wall. Ex Nees (Family: Acanthaceae; Islam, 2017), exhibits various biological activities such as anti-inflammatory (Li et al, 2017;Wang et al, 2019), antivirus (Paemanee et al, 2019;Uttekar et al, 2012), anticancer (Peng et al, 2018;Reabroi et al, 2018;Wei et al, 2018), liver protection (Abdullah & Ismail, 2018), cardiovascular (Wu et al, 2018), and neuroprotective effect (Tao et al, 2018) and is mainly used in clinic for treating cold, fever, gastroenteritis, and upper respiratory tract. The nephrotoxicity of TCM has been reported since the 1980s (Upreti et al, 1989) and has attracted widespread attention (Feng et al, 2018;Song et al, 2018;Vanherweghem et al, 1993).…”