We use cookies to understand how you use our site and to improve your experience. This includes personalizing content and advertising. To learn more, click here. By continuing to use our site, you accept our use of cookies. Cookie Policy.

Features Partner Sites Information LinkXpress hp
Sign In
Advertise with Us
LGC Clinical Diagnostics

Download Mobile App




Leelamine Blocks Melanoma Growth by Disrupting Cellular Cholesterol Transport

By LabMedica International staff writers
Posted on 03 Jun 2014
Print article
An experimental chemotherapeutic drug interferes with intracellular cholesterol transport, which kills melanoma cells by disrupting several molecular pathways simultaneously.

The drug, leelamine, which is a natural compound isolated from pine bark, is a diterpene compound and a weak agonist of the cannabinoid CB1 receptor. The structure of leelamine contains no binding oxygen atoms, underscoring its weak association with the CB1 binding site. Leelamine has been reported to inhibit PDK (pyruvate dehydrogenase kinase) activity.

The PI3 kinase (PI3K), MAP kinase (MAPK), and STAT3 molecular pathways promote disease development by being constitutively activated in 50%–70% of melanomas. To identify a drug capable of simultaneously targeting the PI3K, MAPK, and STAT3 cascades, investigators at the Pennsylvania State University (Hershey, USA) screened 480 compounds from a natural product library. Leelamine was identified as the best potential inhibitor.

Results published in the March 31, 2014, online edition of the journal Molecular Cancer Therapeutics revealed that leelamine inhibited the growth of preexisting xenografted melanoma tumors by an average of 60% by targeting the PI3K, MAPK, and STAT3 pathways without affecting animal body weight or blood markers of major organ function. The mechanism of action of leelamine was mediated by disruption of cholesterol transport, causing decreased cellular proliferation and, consequently leading to increased tumor cell apoptosis as well as decreased tumor vascularization.

"Natural products can be a source of effective cancer drugs, and several are being used for treating a variety of cancers," said senior author Dr. Gavin Robertson, professor of pharmacology, pathology, dermatology, and surgery at The Pennsylvania State University. "Over 60% of anticancer agents are derived from plants, animals, marine sources. or microorganisms. However, leelamine is unique in the way that it acts. To a cancer cell, resistance is like a traffic problem in its circuitry. Cancer cells see treatment with a single drug as a road closure and use a detour or other roads to bypass the closure. The cancer cell is addicted to these pathways, and when they are shut down, the bypass routes cannot be used. The result is the cancer cells die."

Related Links:

The Pennsylvania State University


Gold Member
TORCH Panel Rapid Test
Rapid TORCH Panel Test
Antipsychotic TDM AssaysSaladax Antipsychotic Assays
New
Free Human Prostate-Specific Antigen CLIA
LIAISON fPSA
New
FLU/RSV Test
Humasis FLU/RSV Combo

Print article

Channels

Clinical Chemistry

view channel
Image: The new saliva-based test for heart failure measures two biomarkers in about 15 minutes (Photo courtesy of Trey Pittman)

POC Saliva Testing Device Predicts Heart Failure in 15 Minutes

Heart failure is a serious condition where the heart muscle is unable to pump sufficient oxygen-rich blood throughout the body. It ranks as a major cause of death globally and is particularly fatal for... Read more

Hematology

view channel
Image: The smartphone technology measures blood hemoglobin levels from a digital photo of the inner eyelid (Photo courtesy of Purdue University)

First-Of-Its-Kind Smartphone Technology Noninvasively Measures Blood Hemoglobin Levels at POC

Blood hemoglobin tests are among the most frequently conducted blood tests, as hemoglobin levels can provide vital insights into various health conditions. However, traditional tests are often underutilized... Read more

Immunology

view channel
Image: Under a microscope, DNA repair is visible as bright green spots (“foci”) in the blue-stained cell DNA. Orange highlights actively growing cancer cells (Photo courtesy of WEHI)

Simple Blood Test Could Detect Drug Resistance in Ovarian Cancer Patients

Every year, hundreds of thousands of women across the world are diagnosed with ovarian and breast cancer. PARP inhibitors (PARPi) therapy has been a major advancement in treating these cancers, particularly... Read more

Microbiology

view channel
Image: HNL Dimer can be a novel and potentially useful clinical tool in antibiotic stewardship in sepsis (Photo courtesy of Shutterstock)

Unique Blood Biomarker Shown to Effectively Monitor Sepsis Treatment

Sepsis remains a growing problem across the world, linked to high rates of mortality and morbidity. Timely and accurate diagnosis, along with effective supportive therapy, is essential in reducing sepsis-related... Read more
Copyright © 2000-2024 Globetech Media. All rights reserved.