Harmaline induces apoptosis and inhibits migration in A2780 ovarian cancer cells in vitro.

Ovarian cancer is one of the most prevalent malignancies in women. Harmaline is reported to have powerful anticancer properties. We aimed to investigate the apoptotic and antimetastatic properties of harmaline in A2780 ovarian cancer cells. Cell viability, apoptosis, migration, and invasion were investigated in cells treated with harmaline. Reactive oxygen species (ROS) production, mRNA expression of apoptosis-associated genes, MMP-2, and MMP-9 were measured. Harmaline attenuated the viability of A2780 ovarian cancer cells in a dose- and time-dependent way. Furthermore, compared to NIH/3T3 mouse normal cell line (IC50 = 417 µM), the malignant A2080 cells were more sensitive to harmaline (IC50 = 300 µM after 24 h). Harmaline increased the production of ROS, raised the mRNA expression of p53 and the Bax/Bcl2 ratio. Harmaline also increased the proportion of cells in the late apoptotic and necrotic phases. MMP-2 and MMP-9's mRNA expression, gelatinase activity, and migration of A2780 cells also decreased by harmaline. These findings suggest that harmaline may have the potential to be a therapeutic drug for ovarian cancer by triggering apoptosis and suppressing invasion and migration.

Role of interleukin-6-mediated inflammation in the pathogenesis of inflammatory bowel disease: focus on the available therapeutic approaches and gut microbiome.

Inflammatory bowel disease (IBD) is considered a chronic inflammatory and multifactorial disease of the gastrointestinal tract. Crohn's disease (CD) and ulcerative colitis (UC) are two types of chronic IBD. Although there is no accurate information about IBD pathophysiology, evidence suggests that various factors, including the gut microbiome, environment, genetics, lifestyle, and a dysregulated immune system, may increase susceptibility to IBD. Moreover, inflammatory mediators such as interleukin-6 (IL-6) are involved in the immunopathogenesis of IBDs. IL-6 contributes to T helper 17 (Th17) differentiation, mediating further destructive inflammatory responses in CD and UC. Moreover, Th1-mediated responses participate in IBD, and the antiapoptotic IL-6/IL-6 receptor (IL-6R)/signal transducer and activator of transcription 3 (STAT3) signals are responsible for preserving Th1 cells in the site of inflammation. It has been revealed that fecal bacteria isolated from UC-active and UC-remission patients stimulate the hyperproduction of several cytokines, such as IL-6, tumor necrosis factor-α (TNF-α), IL-10, and IL-12. Given the importance of the IL-6/IL-6R axis, various therapeutic options exist for controlling or treating IBD. Therefore, alternative therapeutic approaches such as modulating the gut microbiome could be beneficial due to the failure of the target therapies so far. This review article summarizes IBD immunopathogenesis focusing on the IL-6/IL-6R axis and discusses available therapeutic approaches based on the gut microbiome alteration and IL-6/IL-6R axis targeting and treatment failure.