"Flavopiridol + nanoparticles" dramatically improves the inhibition of lung cancer cell activity in

Lung cancer is the world's second most prevalent cancer in terms of incidence and the first in terms of mortality.

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for about 80% of all lung cancers. However, about 75% of patients are already at an intermediate to advanced stage at the time of diagnosis and have a low 5-year survival rate. Smoking and chronic inflammation are known to be high-risk factors for developing lung cancer.

Studies over the past few decades have shown that chemicals from cigarette smoke can be toxic to lung cells, causing airway inflammation and accelerating the development of diseases such as cancer, chronic obstructive pulmonary disease and asthma.

Berberine (also known as Huanglianin), an isoquinoline alkaloid isolated from the Chinese medicine Huanglian, has a variety of pharmacological effects, including antibacterial, antidiabetic and anticancer activities. In in vitro experiments, berberine showed significant anti-inflammatory and antioxidant activity. In animal models, the drug has neuroprotective and cardiovascular effects. In addition, the hypolipidemic and insulin resistance-improving effects of berberine have been demonstrated in many randomized clinical trials. Not only that, but it may also have the potential to inhibit lung cancer and reduce inflammation.

In a new study published in Pharmaceutics on May 24, 2022, a research team led by Dr. Kamal Dua, senior lecturer in pharmacy from the University of Technology Sydney, and others demonstrated through in vitro experiments that berberine can inhibit the proliferation of lung cancer cells and also reduce damage to healthy lung cells exposed to cigarette smoke chemicals, as well as airway inflammation.

Dua's team's recent study, published in Antioxidants, shows that berberine inhibits oxidative stress, and inflammation induced by cigarette smoke extracts in laboratory-cultured healthy human lung cells, and delays cellular senescence.

In this new study, the team evaluated the therapeutic effects of berberine in non-small cell lung cancer. The results showed that berberine has strong anti-cancer activity and inhibited the growth of cancer cells in in vitro experiments.

Dua said berberine has a long history in traditional Chinese medicine and Aruvedic medicine, and has long been used as a purgative and antibacterial drug. However, the drug's lack of water solubility has led to low bioavailability in the intestine and toxicity at higher doses, among other problems, thus limiting its therapeutic benefits.

To overcome these difficulties, Dr. Dua developed BP-LCN, a liquid crystal nanoparticle formulation of berberine based on phytanic acid triol. Liquid crystal nanoparticles are an emerging drug delivery system with properties such as improved bioavailability and efficacy, as well as reduced drug toxicity. It has previously been used for safe, effective and controlled delivery of chemotherapeutic drugs.

Researchers have encapsulated berberine in tiny polymer particles that are soluble and biodegradable to improve their safety and efficacy.

In vitro experiments revealed that this phytotriol-based berberine nanoformulation has better drug release properties and is approximately 20 times more potent than free berberine (non-drug delivery) in inhibiting the growth and metastasis of non-small cell lung cancer. Berberine inhibits the production of inflammatory chemicals reactive oxygen species and also regulates genes related to inflammation, oxidative stress, and reduces premature cellular senescence.

Subsequently, they determined the potential mechanism of action of BP-LCN agents by measuring the mRNA levels and protein expression levels of tumor-associated genes PTEN, P53 and KRT18. They found that BP-LCN reduced the proliferation, migration and formation activity of non-small cell lung cancer cells in a dose-dependent manner by upregulating the mRNA expression of PTEN and P53 and downregulating the mRNA expression of KRT18. Also, the agent reduced the expression of proteins associated with cancer cell proliferation and migration.

The researchers said that the BP-LCN formulation could potentially address the low solubility, low oral bioavailability, low efficacy and adverse side effects of free berberine. Therefore, it is a promising candidate for the treatment of lung cancer.

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