Cordiaquinone B induces cytotoxicity and oxidative stress-mediated apoptosis in human colorectal cancer cells invitro and invivo.

Cordiaquinones are natural molecules derived from the Varronia and Cordia genera with diverse biological potential. In this work, the effects of Cordiaquinone B were initially evaluated in a panel of cancer cell lines. Subsequently, it was first-hand investigated both in vitro and in vivo in human colorectal adenocarcinoma (HCT-116) cells. Experiments were conducted using two-dimensional (2D) and three-dimensional (3D) cell cultures and in the HCT-116 xenograft model in immunodeficient CB17-SCID mice. Cordiaquinone B inhibited the viability of both adherent and non-adherent cancer cell lines without inducing hemolysis in human erythrocytes. In Cordiaquinone B-treated HCT-116 cells, morphological changes and alterations in apoptosis-related protein levels were observed, indicating an apoptotic mechanism associated with mitochondrial oxidative stress. This was supported by an increased mitochondrial superoxide content and prevention of observed cytotoxic and apoptotic effects by N-acetylcysteine (NAC) pretreatment. In the 3D tumor model of HCT-116 spheroids, Cordiaquinone B treatment led to a spheroid size reduction. Additionally, in CB17-SCID mice, a dose of 3 mg/kg/day inhibited HCT-116 tumor growth by 42.6 % without causing severe organ toxicity or alterations in hematological parameters, except for mild to moderate hepatic and pulmonary alterations. These results demonstrate the efficacy of Cordiaquinone B and highlight its potential as a promising candidate for colorectal cancer therapy.