Gold nanoparticle resveratrol complex increases apoptosis in KRAS mutant pancreatic cancer cells
Seung Myun Hong1, Deok Jae Lee1, Dong Gun Lee1
1Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea.
Abstract:
The KRAS G12D mutation is the most prevalent type of pancreatic cancer and is found in about 35% of patients. Numerous natural chemicals are frequently investigated in cancer treatment to decrease side effects. Resveratrol (RVT) is a polyphenol that can promote cancer cell apoptosis and improve chemotherapy efficacy in cancers. To enhance delivery rate and efficacy, the size of about 30 nm gold nanoparticles (GNPs) was synthesized and conjugated to resveratrol via polyvinylpyrrolidone (GRs) for high bioavailability. Compared to RVT and GNPs, GRs had less inflammatory response and less toxicity on RAW 264.7 cells. This suggests that the toxicity of resveratrol can be alleviated by conjugation with gold nanoparticles. The viability of the human pancreatic cancer cell line (AsPC-1) decreased in sequence of GRs > RVT > GNPs, suggesting an enhanced anticancer effect of the GRs compared to resveratrol (RVT) alone. In addition, the extent of apoptosis was much bigger with GRs compared to RVT and GNPs. The apoptotic effects were confirmed with cell cycle arrest and expression of apoptosis-related genes and proteins. Thus, GRs had a better extent of anticancer effect than RVT, suggesting that GRs be considered as one of the prospective anti-cancer drugs for pancreatic cancer treatment.
Insights
Gold nanoparticles conjugated with resveratrol (GRs) show reduced toxicity and enhanced anticancer effects against pancreatic cancer cells. This novel formulation, GRs, offers a promising therapeutic strategy for KRAS G12D-mutated pancreatic cancer.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Oncology
Background:
- KRAS G12D mutation is a primary driver in pancreatic cancer, affecting approximately 35% of patients.
- Resveratrol (RVT), a natural polyphenol, exhibits anticancer properties including apoptosis induction and enhanced chemotherapy efficacy.
- Developing effective drug delivery systems is crucial to improve bioavailability and reduce side effects of natural compounds like RVT.
Purpose of the Study:
- To synthesize and characterize resveratrol-conjugated gold nanoparticles (GRs) for enhanced pancreatic cancer treatment.
- To evaluate the in vitro toxicity and anti-proliferative effects of GRs compared to RVT and gold nanoparticles (GNPs) alone.
- To investigate the mechanism of action of GRs, including apoptosis induction and cell cycle effects.
Main Methods:
- Synthesis of ~30 nm gold nanoparticles (GNPs) conjugated with resveratrol (RVT) via polyvinylpyrrolidone (GRs).
- In vitro assessment of toxicity and inflammatory response on RAW 264.7 cells.
- Evaluation of cell viability and apoptosis induction in human pancreatic cancer cell line (AsPC-1).
- Analysis of cell cycle arrest and expression of apoptosis-related genes and proteins.
Main Results:
- GRs exhibited significantly lower toxicity and inflammatory response compared to RVT and GNPs.
- GRs demonstrated a superior anticancer effect on AsPC-1 cells, leading to a greater decrease in cell viability than RVT or GNPs.
- GRs significantly enhanced apoptosis induction, confirmed by cell cycle arrest and modulation of apoptosis-related markers.
Conclusions:
- Resveratrol conjugation with gold nanoparticles (GRs) effectively alleviates RVT toxicity while enhancing its anticancer efficacy.
- GRs represent a promising nanotherapeutic approach for treating KRAS G12D-mutated pancreatic cancer.
- The enhanced apoptotic effects of GRs warrant further investigation as a potential anti-cancer drug candidate.
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