Psychopharmacology

Paeonol triggers apoptosis in HeLa cervical cancer cells: the role of mitochondria-related caspase pathway

Paeonol is a biologically active component purified from the root bark of Cortex Moutan that exerts pharmacological effects on the cervical cancer. In this study, we aim to evaluate the anti-cervical cancer capacity of paeonol and to investigate the mechanism driving its anti-cervical cancer effect. Paeonol administration markedly restrained the proliferation and caused apoptosis in HeLa cells. Furthermore, paeonol treatment resulted in a mitochondrial dysfunction in HeLa cells, including the inducing of mitochondrial membrane potential (MMP), reactive oxygen species (ROS) production, and the release of cytochrome c. Moreover, the Bcl-2/Bax proportion was obviously downregulated and cleaved caspase-3 expression was evaluated through paeonol treatment. Additionally, the expression of p-PI3K and p-Akt was noticeably reduced in response to paeonol treatment in HeLa cells. Our findings indicated that paeonol exerts an anticancer potential in HeLa cells, at least in a manner, via triggering the mitochondrial pathway of cellular apoptosis by inhibiting PI3K/Akt signaling. Thus, paeonol has great potential as a promising therapeutic compound to resist human cervical cancer.

Decoding the genetic links between substance use disorder and cancer vulnerability

Cancer remains a leading cause of mortality and morbidity worldwide, imposing a significant public health burden. While cannabis and opioids are widely used in cancer pain management, their potential for abuse and addiction has raised concerns regarding their long-term health effects, including possible associations with cancer risk. However, the relationship between substance use disorders (SUDs) and cancer susceptibility remains controversial. This Mendelian randomization (MR) study aimed to investigate the potential causal effects of cannabis use disorder (CUD) and opioids use disorder (OUD) on cancer vulnerability. We conducted a two-sample MR study using summary statistics from genome-wide association studies, including data from FinnGen and UK Biobank. The primary analytical approach was the inverse-variance weighted (IVW), complemented by a range of sensitivity analyses to assess the robustness of the findings. IVW analysis identified a causal association between OUD and bladder cancer (OR = 1.040, 95% CI 1.004-1.078, P = 0.029, adj. P = 0.125), acute myeloid leukemia (OR = 0.931, 95% CI 0.885-0.978, P = 0.005, adj. P = 0.061) and ovarian cancer (OR = 0.937, 95% CI 0.891-0.984, P = 0.010, adj. P = 0.064). Sensitivity analysis yielded directionally consistent results. Reverse MR analysis provided no statistically significant evidence supporting a causal effect of these cancers on OUD (all P > 0.05). Additionally, no evidence of a significant causal relationship was observed between CUD and any cancer type (P > 0.05). This study suggests a potential causal link between OUD and increased susceptibility to bladder cancer, acute myeloid leukemia, and ovarian cancer, warranting further investigation in larger, multi-ethnic population studies. These results contribute to the ongoing discourse on the long-term health impacts of substance use disorders and highlight the need for further research to elucidate their potential oncogenic effects.