![]() ![]() ![]() BA exhibits anti-pancreatic cancer effects by suppressing pancreatic cancer growth and inducing apoptosis through the stress-activated protein kinase/mitogen-activated protein kinase/nuclear factor-κB/signal transducer and activator of transcription 3/B cell lymphoma-2 (JNK/p38 MAPK/NF-κB/Stat3/Bcl-2) signaling pathway ( Lu et al., 2021). Studies have demonstrated that BA concurrently exerts a multitude of biological properties, including suppression of tumor cell growth, reduction of malaria para-locus replication, alleviation of inflammation, and resistance to viral invasion ( Feng et al., 2010 Wang et al., 2011). Therefore, it is of significantly scientific and clinical implications to investigate the efficacy and mechanism of action of highly potent and low-toxic antitumor substances from TCM components on CC.īruceine A (BA) is a kind of active nigakilactone ingredient isolated from TMC Brucea javanica ( Nakao et al., 2009). An increasing amount of effective ingredients in traditional Chinese medicine (TCM) have been discovered and applied into various diseases ( Amin et al., 2011 Li et al., 2017 Al-Dabbagh et al., 2018 Hamza et al., 2020 Pan et al., 2021 Ren et al., 2021 Chen et al., 2022 Sun et al., 2022 Zuo et al., 2022). Currently, the conventional surgery is the primary treatment for CC, whereas radiotherapy, chemotherapy, and drug combination therapy are frequently adopted main treatments for advanced CC, yet recurrence, toxin accumulation, and drug resistance are the principal disadvantages of these treatments ( Bagheri et al., 2018 Siddiqui et al., 2018 Van der Jeught et al., 2018 Wegner et al., 2020 Wang et al., 2021a Wang et al., 2021b). Taken together, our results demonstrated that BA might be a promising chemotherapy drug in the treatment of CC.Ĭolon cancer (CC) is one of the most prevalent gastrointestinal malignancies, with the third highest incidence and the fourth highest mortality rate in the world, as well as increasing morbidity in the last decade ( Siegel et al., 2020). Further mechanistic studies revealed BA impacted cell cycle-related proteins by regulating the expression of P27 (a protein bridging the PI3K/Akt signaling pathway with cycle-related proteins), arresting the cell cycle in the G2 phase, inhibiting the proliferation of HCT116 and CT26, and facilitated the apoptosis in CC cells by activating the mitochondria-associated apoptosis protein Bax and accumulating reactive oxygen species, in addition to BA apparently inhibited the migration of CC cells. BA remarkably suppressed the proliferation of CC cells HCT116 and CT26 with 48-h IC50 of 26.12 and 229.26 nM, respectively, and the expression of p-PI3K/p-Akt was restrained by BA at the molecular level as verified by Western blot assay. Meanwhile, molecular docking results implied that BA could conjugate to pivotal proteins in the PI3K/Akt pathway. The network pharmacology research indicated that Akt1 and Jun and PI3K/Akt pathways are the predominant targets and critical signaling pathways, respectively, for BA treatment of CC. In this study, we investigated the anticancer effects of BA on CC cells and the underlying mechanisms. 4Department of Physiology, School of Basic Medical Sciences, Shenzhen University, Shenzhen, Chinaīruceine A (BA), a quassic ester from bruceine javanica, regulates diverse intracellular signal transduction pathways and manifests a variety of biological activities, however, its pharmacological mechanism in treating colon cancer (CC) is unclear.3Clinical Research Center, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China.2Department of Dermatology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.1State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.Chaozheng Zhang 1 †, Yuening Cao 1 †, Yi Zuo 1 †, Hongbin Cheng 1,2, Changqun Liu 1, Xila Xia 1, Bo Ren 1, Yun Deng 1, Maolin Wang 3,4* and Jun Lu 1*
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