Abstract
BackgroundPancreatic cancer is aggressive with no symptoms until the advanced stage reached. The increased resistance of pancreatic cancer to chemotherapy demonstrates a dilemma in the clinical field. Hence, it is a matter of great urgency to develop an effective drug to treat patients with pancreatic cancer. Betulinic acid is a major triterpene isolated from spina date seed. Several studies have suggested its low toxicity and side effects to patients with malaria and inflammation. However, relevant studies on betulinic acid in inhibiting cancer were insufficient and the molecular mechanism was unclear. This study aimed to systematically explore the potential anti-cancer functions of betulinic acid in pancreatic cancer, and investigate its underlying molecular mechanism.MethodsThe Counting Kit-8 assay, colony formation, transwell invasion assay, wound healing assay, flow cytometry and xenograft nude mice model were used to evaluate the effect of betulinic acid on the proliferation, invasion and migration ability of pancreatic cancer cells.ResultsOur results showed that betulinic acid obviously suppressed pancreatic cancer both in vitro and in vivo in a dose-dependent manner. We also determined that betulinic acid inhibited pancreatic cancer by specifically targeting mTOR signaling rather than Nrf2 or JAK2.ConclusionsThese findings clarify that betulinic acid is a potential and valuable anticancer agent for pancreatic cancer, and indicate the specific molecular target of betulinic acid.
Highlights
Pancreatic cancer is aggressive with no symptoms until the advanced stage reached
A major natural product extracted from spina date seed, exhibits multiple biological activities such as anti-malarial, antiinflammatory and anti-human immunodeficiency virus (HIV) [4]
Real-time Cellular Analysis System (RTCA) showed that the cell proliferation of PANC-1 and SW1990 reduced remarkably after treatment with 20 and 60 μM betulinic acid than the DMSO
Summary
The increased resistance of pancreatic cancer to chemotherapy demonstrates a dilemma in the clinical field. It is a matter of great urgency to develop an effective drug to treat patients with pancreatic cancer. Betulinic acid is a major triterpene isolated from spina date seed. Relevant studies on betulinic acid in inhibiting cancer were insufficient and the molecular mechanism was unclear. This study aimed to systematically explore the potential anti-cancer functions of betulinic acid in pancreatic cancer, and investigate its underlying molecular mechanism. A major natural product extracted from spina date seed, exhibits multiple biological activities such as anti-malarial, antiinflammatory and anti-HIV [4]. Steele et al have suggested that betulinic acid can be an anti-malarial
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