Isoquinocycline B induces G0/G1 cell cycle arrest and apoptosis in MDA-MB-231 cancer cells

Breast cancer remains one of the leading causes of cancer-related deaths, with therapeutic resistance and limited treatment options posing significant challenges. This study investigated the anticancer properties of isoquinocycline B (IQCB), an anthraquinone derivative obtained from a freshwater sponge microbiome Micromonospora sp. MS-62 (FBCC-B8445), against the MDA-MB-231 human breast cancer cell line. IQCB showed the greatest activity against cytotoxicity with an IC₅₀ values of 9.2 ± 1.0 μM. IQCB treatment led to G0/G1 cell cycle arrest and apoptosis through mitochondrial pathways by suppressing cyclin D1/CDK4 expression, enhancing p27 levels, and reducing phosphorylated Akt levels. Furthermore, IQCB induced oxidative stress by promoting excessive reactive oxygen species (ROS) production, thereby activating JNK and p38-MAPK signaling while simultaneously inhibiting ERK phosphorylation. Apoptotic markers such as PARP cleavage and caspase-3 activation confirmed that mitochondrial-mediated apoptosis was a key mechanism of action. These results highlight the potential of IQCB as a therapeutic candidate for breast cancer and underscore the need for further research to explore its efficacy and mechanisms.