Myung Chul Cha¹, Dong Seok Lee^{1, 2,}

With the development of health technology, effective treatments for many types of cancer have been developed and contributed to increasing the survival rate of cancer patients, but pancreatic cancer still has a very low survival rate. In this study, the effect of ethyl acetate (EtOAc) fraction from Opuntia humifusa on PANC-1 human pancreatic cancer cells was investigated. The extract was obtained by treating the fruit powder of O. humifusa with 50% EtOH, and then the EtOAc fraction was selected to conduct this study. The PANC-1 cells cultured in Dulbecco’s modified Eagle’s medium (DMEM) with fetal bovine serum and penicillin were seeded on a 96 well plate, cultured for 24 h, and treated with EtOAc fraction for 12 to 72 h. 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay confirmed that cancer cells were reduced by more than 50% in the experimental group treated with EtOAc fraction for 48 h compared to the control group. In order to explore the signal transduction pathway in anti-cancer activity, western blotting was performed. ERK1/2 and Akt, enzymes involved in the upstream signaling pathway directing cell proliferation and invasiveness were reduced by the EtOAc fraction compared to the control. Cleaved caspase-3, a representative effector caspase involved in apoptosis was increased compared to the control by the EtOAc fraction. The EtOAc fraction extensively induced apoptosis through extrinsic, intrinsic, and ER-stress signaling pathways. Effective anti-pancreatic cancer activity was achieved by treating PANC-1 cells with EtOAc fraction through reduction of poly (ADP-ribose) polymerase (PARP), a necessary factor for cell repair, lamin A/C, a major component of nuclear membrane structures, and CDK4, which is required to start the G1/S phase in the cell cycle. In conclusion, it was found that the EtOAc fraction from O. humifusa inhibited the proliferation, invasiveness, cell cycle progression, and cell repair ability of PANC-1 pancreatic cancer cells, while effectively inducing apoptosis of them through extrinsic, intrinsic, and ER-stress signaling pathways.

Opuntia humifusa, PANC-1, apoptosis, cell cycle arrest, signaling pathways