Cucurbitacin B inhibits cell proliferation and induces apoptosis in human osteosarcoma cells via modulation of the JAK2/STAT3 and MAPK pathways

Abstract

Abstract. Osteosarcoma (OS) is the most commonly diagnosed tumor of the bones in children and young adults. Even with conventional therapies the 5-year survival rate is ~65% in patients with OS. Considering the side effects and aggressiveness of malignant bone tumors, research is focussing on multi-targeted strategies in treatment. Cucurbitacin B, a triterpenoid compound has been demonstrated to induce apoptosis in various cancer cell types. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling cascades and mitogen activated protein kinases (MAPK) signalling cascades are critical regulators of tumorigenesis. The present study assessed the influence of cucurbitacin B on the viability and expression of MAPKs and proteins of the JAK2/STAT3 cascades in human OS cells (U-2 OS). Cucurbitacin B (20-100 µM) significantly reduced cell viability (P<0.05) and induced apoptosis, as assessed by MTT and Annexin V/propidium iodide staining, along with inhibiting cell migration. Gelatin zymography revealed supressed activities of matrix metalloproteinase (MMP-)2 and 9. Furthermore, cucurbitacin B effectively upregulated the apoptotic pathway and caused the effective inhibition of MAPK signalling and JAK2/STAT3 cascades. Multifold suppression of vascular endothelial growth factor by cucurbitacin B was also observed, indicating inhibition of angiogenesis. Thus, by downregulating major pathways-MAPK and JAK2/STAT3 and MMPs, cucurbitacin B has potent anti-proliferative and anti-metastatic effects that require further investigation with regards to cancer treatment.

Cytisine exerts anti-tumour effects on lung cancer cells by modulating reactive oxygen species-mediated signalling pathways

“…cell proliferation and growth. In contrast, JNK and p38 are induced by cellular stress and are closely associated with cell death [23,24]. NF-jB and STAT3 signalling pathways play pivotal roles in the cellular transcription process in a number of malignancies.…”

Change in Bitterness, Accumulation of Cucurbitacin B and Expression Patterns of CuB Biosynthesis-related Genes in Melon During Fruit Development

“…Topical application of CuB resulted in significant reduction of epidermal hyperplasia and inflammatory cytokines, and ameliorated psoriatic symptoms (Li et al, 2015). Natural cucurbitacins and their derivatives have been recognized as promising antitumor compounds for several types of cancer, including Non-small cell lung cancer (Marostica et al, 2017), Osteosarcoma (Zhang et al, 2017) and gastric cancer (Liu et al, 2017).…”

Cucurbitacin B inhibits the migration and invasion of breast cancer cells by altering the biomechanical properties of cells

“…CuB has a wide range of pharmacological effects such as anti-inflammatory, antiviral, anticancer, and other activities (Garg, Kaul, & Wadhwa, 2018;Chen, Chiu, Nie, Cordell, & Qiu, 2005;Jayaprakasam, Seeram, & Nair, 2003). In recent years, many studies have reported that CuB can inhibit cell proliferation and induce apoptosis of different types of cancer cells, and it has become a potentially safe anticancer drug (Chen et al, 2012;Promkan, Dakeng, Chakrabarty, Bogler, & Patmasiriwat, 2013;Shukla et al, 2015;Zhang, Gao, & Yang, 2017). Previous studies have shown that CuB interacts with the cytoskeleton by affecting actin filaments and the microtubule, and the cytoskeleton appears to be an early target (Wang, Tanaka, Peixoto, & Wink, 2017;Zhang et al, 2014).…”