Curcumin-like structure (CCA-1.1) induces permanent mitotic arrest (Senescence) on Triple-negative breast cancer (TNBC) cells, 4T1

Abstract

Triple-negative breast cancer (TNBC) remains as the deadliest cancer type due to the lack of treatment options. Hence, several attempts have been made to develop new anticancer for TNBC therapy. This study intended to challenge curcumin analog (CCA)-1.1, which is derived from pentagamavunone-1 structure, against the 4T1 cell line and TNBC cell model, covering the cytotoxic activity in correlation with cell cycle progression, apoptosis induction, reactive oxygen species (ROS) generation, and senescence evidence. The cell viability, cell cycle profile, apoptosis induction, intracellular ROS level, and senescence induction were determined in vitro using trypan blue exclusion, propidium iodide (PI) staining, Annexin-PI staining, dichlorofluorescein diacetate staining, and senescence-associated-β-gal method. CCA-1.1 showed cytotoxic activity on 4T1 cells, giving half maximal inhibitory concentration value of 3M, but was less toxic on non-cancerous 3T3-L1 cells. CCA-1.1 induced rapid cell death and inhibited cell cycle progression at the mitotic phase. Instead, of causing apoptosis, CCA-1.1 induced mitotic catastrophe. Furthermore, CCA-1.1 itself increased the intracellular ROS level and induced senescence, possibly through catastrophic cell death. Altogether, our preliminary study strengthens the potency of CCA-1.1 for its anticancer activities against TNBC cells and prospective to be pharmaceutically developed as a novel candidate for cancer therapy.