Charakterystyka potencjału przeciwnowotworowego kwasu roburowego

Abstract

Roburic acid (RA), a tetracyclic triterpenoid, has demonstrated antiproliferative and anti-inflammatory properties, although its cellular mechanisms remain incompletely understood. This doctoral research aimed to characterize the anticancer activity of RA, with particular emphasis on colorectal cancer (CRC), and to identify the mechanisms underlying its effects on cell proliferation and survival. RA activity was initially evaluated in human cancer and non-malignant cell lines, followed by mechanistic studies in DLD-1, HCT-116, and HT-29 cells. RA inhibited cancer cell growth in a concentration- and time-dependent manner, with CRC cells exhibiting relatively high sensitivity. Reduced DNA synthesis, clonogenic capacity, and proliferation markers, together with G0/G1 cell cycle arrest, indicated a predominantly cytostatic effect. RA also attenuated TNF-α-induced NF-κB transcriptional activity and decreased mitochondrial membrane potential without inducing oxidative stress or DNA damage. Although apoptotic features and caspase-9 activation were detected under certain conditions, pharmacological inhibition of apoptosis, necroptosis, or ferroptosis did not reverse RA-induced growth inhibition. Furthermore, RA did not induce cellular senescence. Changes in P53 and P21 expression and subcellular localization suggested cell line-dependent modulation of cell cycle regulatory mechanisms. Complementary in silico analyses identified potential molecular targets, including CAII, CES1, EGFR, and PLA2G2A. Overall, RA primarily suppresses CRC cell proliferation through cytostatic mechanisms, while mitochondrial dysfunction and apoptosis represent secondary, context-dependent responses. These findings support further investigation of RA as a potential anticancer lead compound.