EXPLORING THE ANTI-CANCER ACTIVITIES OF STILBENE ANALOGUES AND DERIVATIVES
Stilbenes, defense compounds produced by plants including red grapes, peanuts, and blueberries, have been popularized in recent years based on observed health benefits. Resveratrol is the most widely studied stilbene, due to the high content in red wine linked with cardiovascular health. Additional studies have revealed resveratrol to possess significant antioxidant and anti-cancer effects. Many stilbenes are classified as phytoestrogens due to their ability to bind and alter the activity of the estrogen receptor; however, unlike estrogen, do not appear to negatively impact breast and reproductive organs. Stilbenes thus represent a novel option for cancer therapeutic development. Currently, a series of more than 30 novel analogues are being screened to determine effects on cell proliferation, viability, morphology, and motility in both estrogen receptor positive and negative cell lines. Compounds identified as active will be further tested to determine the effective dose range and mechanism of action.
DETERMINING THE EFFECTS OF ESSENTIAL OILS ON CANCER CELLS
Essential oils are naturally occurring aromatic compounds derived from plants giving them their aroma. Medicinal use of essential oils dates back centuries but has recently made a comeback within the natural remedies movement. Many drugs are developed from natural compounds, from Tylenol to Penicillin, and several essential oils have shown promise as anti-cancer compounds. The majority of research on essential oils and cancer have focused on palliative care, but a few essential oils have been shown to have therapeutic activity. We have acquired a library of 52 pure essential oils that are commercially available and widely used for many common ailments with little if any reported side effects. The focus of this proposed research is to identify essential oils with anti-cancer activity against triple-negative breast cancers and to determine the effective dose range of each active compound.
UNRAVELING THE ROLE OF EXTRACELLULAR MATRIX COMPOSITION AND ARCHITECTURE IN PANCREATIC CANCER
Pancreatic ductal adenocarcinoma (PDAC) is one of the most stromal-rich cancers with structural components (ie. non-cancer cells) composing up to 90% of the tumor mass. One of the most extensive components of tumor stroma is the extracellular matrix (ECM), involved in maintaining tissue structure, cellular signaling, and regulation of tissue remodeling in normal and diseased tissues. The goal of this proposal is to determine if differences in ECM composition and architecture exist between normal pancreatic and PDAC tumor tissue using a decellularization model (removal of cells from the ECM). The overall purpose of this work is to demonstrate measurable differences in tumor tissue architecture and composition between normal and cancer tissue and determine the effects of these differences of pancreatic cancer cell transformation and progression to more advanced phenotypes.
NONCODING RNA REGULATION OF BREAST CANCER METASTASIS
Focusing on the molecular basis of breast cancer, this project is examining the mechanisms of non-coding RNA interactions that regulate cancer progression and metastasis. Bioinformatic analyses revealed potential crosstalk between the metastasis associated long noncoding RNA (lncRNA) HOTAIR and microRNA (miRNA) associated with cancer progression. Manipulation of the estrogen receptor positive (ER+) cell line, MCF-7, allowed for the investigation of HOTAIR’s effects on cancer proliferation, motility, morphology, and gene expression. Additionally, multiple splice variants of HOTAIR have been identified, each with binding sites to a different set of miRNA, indicating the isoforms may induce divergent regulatory pathways. This project will continue to utilize traditional bench research with cutting-edge bioinformatics techniques to fully understand how non-coding RNA regulate cancer progression in the hopes of identifying new therapeutic targets.
ATTACKING CANCER AT THE NANO-SCALE WITH NOBLE-METAL NANOPARTICLES
Nanoparticles (NPs) possess distinctive physicochemical properties, promising a wide variety of applications, ranging from design of consumer products to effective disease diagnosis and treatment. Their small sizes allow them to enter living cells and organisms. The mechanisms of NP reactivity are still unknown, despite their interactions with live cells and embryos being extensively studied. The effects observed in previous studies using gold (Au) or silver (Ag) NPs offer the possibility of noble-metal NPs use as unconventional therapeutic approaches for targeting of cancer cells. Our focus is on the design of model NPs for in vivo and in vitro analysis of transport, biocompatibility and toxicity of noble-metal NPs. In the lab, we synthesized spherical Au NPs and Ag NPs with an average diameter of 4 nm and 12 nm respectively, which were stable (non-aggregated) in biological medias. We are currently optimizing green synthesis for a non-toxic but reliable production. Our localized surface plasmon resonance (LSPR) spectra and scattering intensity methods using dark-field optical microscopy and spectroscopy (DFOMS) allow us to characterize single NPs in living embryos and cells in real-time at nanometer resolution. Due to their immortal nature, cancer cells grow indefinitely and are excellent cellular models to study NP effects on cell growth and development. We are in the process of testing NPs in cancer cells to determine the uptake and transport, and comparing size and concentrations effects on cell proliferation and viability.
FOR MORE INFORMATION ON DR. CHOU'S AND DR. LEE'S NANOPARTICLE RESEARCH, CHECK OUT THEIR MOST RECENT ACS JOURNAL PUBLICATION:
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