Abstract
Pancreatic cancer is considered a lethal and treatment-refractory disease. To obtain a potent anticancer drug, the cytotoxic effect of 2-(benzo[d]oxazol-3(2H)-ylmethyl)- 5-((cyclohexylamino)methyl)benzene-1,4-diol, dihydrochloride (NSC48693) on human pancreatic cancer cells CFPAC-1, MiaPaCa-2, and BxPC-3 was assessed in vitro. The proliferation of CFPAC-1, MiaPaCa-2, and BxPC-3 is inhibited with IC50 value of 12.9±0.2, 20.6±0.3, and 6.2±0.6 µM at 48 h, respectively. This discovery is followed with additional analysis to demonstrate that NSC48693 inhibition is due to induction of apoptosis, including Annexin V staining, chromatins staining, and colony forming assays. It is further revealed that NSC48693 induces the release of cytochrome c, reduces mitochondrial membrane potential, generates reactive oxygen species, and activates caspase. These results collectively indicate that NSC48693 mainly induces apoptosis of CFPAC-1, MiaPaCa-2, and BxPC-3 cells by the mitochondrial-mediated apoptotic pathway. Excitingly, the study highlights an encouraging inhibition effect that human embryonic kidney (HEK-293) and liver (HL-7702) cells are more resistant to the antigrowth effect of NSC48693 compared to the three cancer cell lines. From this perspective, NSC48693 should help to open up a new opportunity for the treatment of patients with pancreatic cancer.
Highlights
Pancreatic cancer is considered an aggressive cancer since it usually goes undetected until it reaches the late stage [1]
The uncovered chemotherapeutic drugs have yet to achieve any real progress in clinical therapy so far, the chemotherapy is still a backbone in the treatment of advanced pancreatic cancer at present [25]
We focused on evaluating the effect of NSC48693 on the death by inducing apoptosis of human pancreatic cancer cells CFPAC-1, MiaPaCa-2, and BxPC-3 in vitro
Summary
Pancreatic cancer is considered an aggressive cancer since it usually goes undetected until it reaches the late stage [1]. It is regretful that little convincing results are found on clinically relevant improvements in quality of life and survival. To address this issue, there appears to be an urgent need for the development of new anticancer drugs. The active GTPbound Ras is in equilibrium with three distinct states, one of which is the open non-signaling conformation that is a transient intermediate during GTP hydrolysis [11]. This implies that the Ras intermediate is a convergent point for survival signaling in pancreatic cancer. Little efforts focus on the effect of NSC48693 on pancreatic cancer, it offers a selected choice of high quality inducer of apoptosis
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