EXPLORING THE BREAST CANCER-TARGETTING ABILITIES OF A PLANT-BASED COMPOUND

Breast cancer is the most prevalent type of cancer in the world and a particular challenge in the UAE. The World Health Organization reported that 2.3 million women were diagnosed with breast cancer in 2020, and 685,000 died from the disease. In the UAE, cancer is the third leading cause of death after heart disease and road accidents.

While breast cancer is common, it remains a particularly challenging type of cancer to eradicate, necessitating ongoing research to develop better treatments. What makes breast cancer treatment especially problematic is the fact that breast cancer is one of the more heterogeneous cancers.

This means that not only do breast cancer patients have varied disease profiles – with cancer originating in different types of cells and spreading and growing in different ways – but even within a single patient, the breast cancer can contain many different cell populations with their own growth rates, dispersal, and susceptibility to treatment.

This often causes breast cancers to resist the available chemotherapies, requiring the development of new treatments able to target various vulnerabilities. Given the ubiquity of breast cancer locally and worldwide, and the challenge of treating it, a team of researchers led by Dr. Cijo George Vazhappilly, Assistant Professor of Biotechnology at the American University of Ras Al Khaimah (AURAK), investigated the breast cancer-fighting potential of a chemical compound called catechol.

Catechol is a naturally occurring compound found in fruits and vegetables such as onions, apples, and olive oil. Previous research has found catechol can kill or damage some brain and lung cancers, suggesting it may have breast cancer treatment potential.

“Catechol has recently shown significant chemotherapeutic effects in various cancer models. It appears to be able to induce the killing effect on cancer cells while having less effect on the normal cells, making it a special candidate in the drug discovery process. As breast cancer is one of the leading cancers worldwide, we intended to investigate catechol’s efficacy and mode of mechanism to combat breast cancer progression,” Dr. Vazhappilly explained.

His collaborators from AURAK included Assistant Professor of Medical Biotechnology Dr. Rawad Hodeify, Assistant Professor of Biotechnology Dr. Shoib Sarwar Siddiqui, Biotechnology Department Chair and Associate Professor of Biotechnology Dr. Rachel Matar, Associate Dean and Associate Professor of Biology Dr. Maxime Merheb, Instructor John Marton, and Laboratory Technician Hussain Abdel Karim Al Zouabi. External collaborators included Professor of Pharmacology Dr. Raafat El- Awady, PhD student Amina Jamal Laham, and research assistant Varsha Menon from the University of Sharjah, and Professor of Pharmacology Dr. Rajan Radhakrishnan from the Mohammed Bin Rashid University of Medicine and Health Sciences. They recently published a paper on their project in the journal Phytotherapy Research.

The team sought to test the chemotherapeutic efficacy of catechol, examining its effect on DNA damage, cell cycle progression, and the cell death process in breast cancer cells. All cells go through the cell cycle, which is a sequence of cell growth, DNA replication, and then cell division. Throughout the cell cycle, there are many points at which the body checks the cell for damage. If any damage is found, the cell attempts to repair itself. If it cannot be repaired or is too old, then it receives a signal to initiate programmed cell death through self-destruction. Cancer occurs when this automatic process breaks down. The cancer cells may evade quality checks, enabling them to proliferate despite having errors or mutations, and even ignore the automatic signal to initiate cell death.

Inducing DNA damage in a cancer cell is one strategy for combating cancer, as it can trigger permanent cell cycle arrest or apoptosis. Hindering cell cycle progression is another way of halting the production of cancer cells, as it can artificially halt a cell’s progression through the cell cycle.

Being able to trigger cell death in cancer cells is another strategy to eradicate cancer. To test catechol’s effect on cells, the team grew two human breast cancer cell lines and two normal human cell lines (one from human fibroblast and one from human kidneys) for comparison. They then tested how DNA damage, cell cycle progress, and programmed cell death were impacted in all four cell lines when exposed to varied doses of catechol over a 48 hour period. A second set of cells were also exposed to doxorubicin, a standard chemotherapy drug, to see how catechol’s effects compared to an available treatment.

“Analyzing a dose-responsive cytotoxic effect is crucial prior to investigating the molecular mechanisms for any chemotherapeutic agent. Even though the effect of higher catechol concentrations has been previously described in different cell lines, it is essential to understand its side effects on normal cells during chemotherapy,” Dr. Vazhappilly said.

The investigation found that at moderate concentrations, catechol was toxic to the treated cancer cells and was able to target multiple signaling cascades within the cell. Catechol was specifically able to trigger cell cycle arrest within the breast cancer cells, a type of cell damage called a double-strand break, as well as apoptosis. concerns and side effects caused by many other drugs, which are currently in use.” Further research is needed to identify the appropriate dose of catechol for breast cancer treatment, which Dr. Vazhappilly and his collaborators are now investigating through live mice studies.