Colorectal cancer (CRC) remains a major clinical challenge owing to its high mortality and limited therapeutic options, highlighting the urgent need for novel anticancer agents. Andrographolide (AGL), the principal bioactive compound isolated from the medicinal herb Andrographis paniculata, has demonstrated promising anticancer activity across multiple malignancies; however, its effects on CRC and the underlying molecular mechanisms remain poorly elucidated. Here, we systematically evaluated the anti-CRC potential of AGL using both in vitro and in vivo models. AGL significantly inhibited the proliferation of HT-29 and HCT-116 CRC cell lines in a dose- and time-dependent manner, induced G1-phase cell cycle arrest, suppressed cell migration, and promoted apoptosis and necrosis as determined by CCK-8 assays, flow cytometry, wound-healing assays, and YO-PRO-1/propidium iodide dual staining. Integrated transcriptomic and proteomic analyses of AGL-treated HT-29 cells revealed extensive gene and protein alterations enriched in pathways governing cell cycle control, apoptosis, and cancer-related signaling, and Western blotting confirmed the upregulation of pro-apoptotic proteins and downregulation of anti-apoptotic proteins. Importantly, AGL also significantly suppressed tumor growth in an HT-29 subcutaneous xenograft mouse model. Collectively, these findings demonstrate that AGL exerts potent anti-CRC activity primarily through the induction of G1-phase arrest and apoptosis, supporting its potential as a promising natural lead compound for the development of novel CRC therapeutics.
Haocheng Guan, Yongchao Li, Menglong Xu et al.· Current Issues in Molecular...· 0 citations
Dry age-related macular degeneration (dAMD) is a leading cause of irreversible vision loss, driven by chronic oxidative stress and inflammation in the retinal pigment epithelium (RPE). Disruption of key negative regulators of the JAK-STAT pathway, particularly SOCS3, contributes to this oxidative-inflammatory cascade. To address this, we developed a dual-restricted ocular gene delivery platform that combines suprachoroidal administration with an RPE-specific Best1 promoter, enabling localized, durable, and cell-restricted SOCS3 expression. Comparative analysis showed that intravitreal injection poorly transduced the RPE, whereas suprachoroidal delivery improved AAV access to the RPE/outer retinal region, and the Best1 promoter further restricted expression to RPE cells, reducing neural retinal off-target expression. In vitro, SOCS3 restoration suppressed STAT3 activation, inflammatory cytokine release, reactive oxygen species accumulation, mitochondrial disruption, and barrier impairment. In vivo, the dual-restricted system achieved long-term, ocular-localized expression for at least six months, reducing microglial/macrophage activation, inflammation, oxidative stress, and apoptosis, thereby preserving outer retinal architecture. Ocular and systemic safety assessments detected no overt toxicity under the tested conditions. Together, these findings support suprachoroidal AAV-Best1-SOCS3 delivery as a dual-restricted platform for localized modulation of oxidative-inflammatory retinal degeneration and warrant further preclinical evaluation.
Yiquan Zhang, F. Luan, Jing Feng et al.· Journal of Controlled Releas...· 0 citations
