Work done in the lab of Dr. Gaurav Das at Chittaranjan National Cancer Institute, Kolkata, India
Subhabrata Guha is a Research Scholar at Chittaranjan National Cancer Institute (CNCI) in Kolkata, India, as a DST-INSPIRE Faculty Project Fellow working under the guidance of Dr. Gaurav Das, DST INSPIRE Faculty, and Dr. Prosenjit Saha, Senior Scientist. The primary focus of his research is to evaluate the potential of various natural products against Triple Negative Breast Cancer (TNBC) and the synthesis of various nanoparticles entrapping the natural products as potential therapeutic agents targeting the Breast Cancer Stem Cells (BCSCs) which is one of the major reasons of tumor relapse associated with TNBC.
Author Interview
How would you explain your research outcomes to the non-scientific community?
In today’s world, TNBC (triple-negative breast cancer) is considered to be the most destructive, invasive, and lethal subtype of known breast cancer due to its extreme metastatic potential, molecular heterogeneity, tendency to relapse, and poor prognosis. Though there are various treatment modalities available against TNBC subtypes such as surgery, radiation therapy, immunotherapy, and chemotherapy, the success rate is still very low. Due to the absence of ER (estrogen receptor), PR (progesterone receptor), and HER2 (human epidermal growth factor receptor 2), TNBC cells are unresponsive to conventional targeted endocrine therapies, and HER2-detected therapies. However, the available medicines for TNBC patients are cisplatin, anthracycline, taxanes, paclitaxel, and tamoxifen but for a long time, they have been developing severe side effects and chemo-resistance. In this scenario, preparing a novel, targeted, non-toxic, and low-cost medicine against TNBC, is the main priority for the researchers.
For this, researchers are now focusing on various plant-based natural products because of their easy availability, non-toxic nature, and cheap price. Due to the presence of numerous complex bioactive phytochemicals within plant-based natural products, they play an indispensable role in the design and development of new drugs. In our research, we have found that Ruellia tuberosa L. plant, commonly known as the ‘cracker plant’ or the ‘popping pod plant’ is an important ethnomedicinal plant predominantly utilized in traditional medication methods. According to our study, the methanolic extract of Ruellia tuberosa L. flower (RTME) has significant cytotoxicity against TNBC cells (MDA-MB-231) in vitro. We have also found that different complex bioactive phytochemicals within RTME may induce cellular apoptosis by targeting mitochondria-dependent ‘intrinsic apoptosis pathway’ via induction of intracellular reactive oxygen species (ROS) and promotion of G0/G1 cell cycle arrest. We have also studied that RTME did not show any toxicity in female Balb/C mice at experimental drug concentrations.
Though it might look like a far-fetched idea and more studies and testing need to be conducted, we think RTME could contain the formula to that wonder drug that can cure a difficult-to-treat cancer like TNBC.
“RTME targets mitochondria-dependent ‘intrinsic apoptosis pathway’ via induction of intracellular reactive oxygen species (ROS) and promotes G0/G1 cell cycle arrest””
How do these findings contribute to your research area?
Currently, in the realm of TNBC research, drug resistance, and tumor relapses are the two major growing concerns for our laboratory. All of us in our team are trying to find ways to manage TNBC and thus any new drug candidate would irk my interest, exactly what happened for RTME. My study emphasized the potential of RTME targeting mitochondria-dependent ‘intrinsic apoptosis pathway’ via induction of intracellular reactive oxygen species (ROS) and promotion of G0/G1 cell cycle arrest. Thus, RTME could be an alternate therapeutic approach for the management of TNBC and that would be a huge finding in our research area.
What was the exciting moment during your research?
The whole journey was filled with excitement, to be honest. From collecting those beautiful violet flowers not exactly knowing what secret ingredients they may be hiding inside, it was like a mystery thriller. Serendipity is always a blessing in science, and you never know when you dissect nature what might come out of it. Our nature holds some of the best-kept secret therapeutic regimens and it is always exciting to walk on a path less traveled. When I first found out that my brownish flower extract could vanquish those TNBC cells, observing those floating dead cancer cells under the microscope made me cry. That was the eureka moment, in that very moment I realized with science I have the power to do the impossible and I am going to find the secret recipe to kill those cancer cells.
What do you hope to do next?
For me, this is just the tip of the iceberg. I would like to further investigate to find out the responsible molecules within RTME and isolate them as pure compounds. Furthermore, my objective will be to develop and synthesize phytochemical-based nanoparticles for better delivery into the TNBC cells.
Where do you seek scientific inspiration from?
My inspiration comes from my mentors, Dr. Gaurav Das, DST INSPIRE Faculty, and Dr. Prosenjit Saha, Senior Scientist at CNCI for their help and immense support. I am immensely thankful to the DST-INSPIRE Faculty Project which has provided me with the research grant and fellowship to pursue this work. I am also thankful to Dr. Avinaba Mukherjee who has continuously encouraged and inspired me throughout my journey with his dedication and passion for the work. He always told me, “Result is not so important but the journey is important”. During this journey, I learned many new exciting skills, but I think I have a long journey ahead of me, and I aim to learn and contribute to the advancement of society and the Indian Science Community.
How do you intend to help Indian science improve?
I do not think science is regional or national, I think it has a much larger context. It belongs to everyone on this planet. An invention, let’s say in my case a cancer drug for curing breast cancer will not only benefit Indian science but I guess science in general as it will inspire researchers across the world to be brave and make discoveries fearlessly without the fear of failure. Failure in science is a must, and we all have failed or will fail at some point but our victories however minute they might be must we learn to celebrate more than our failures. So, I think my discovery will lead researchers across the world and of course my nation toward a new dawn of discovering anti-cancer drugs which will help to eradicate and manage this difficult disease.
Reference:
Guha, S., Talukdar, D., Mandal, G. K., Mukherjee, R., Ghosh, S., Naskar, R., Saha, P., Murmu, N., & Das, G. (2024). Crude extract of Ruellia tuberosa L. flower induces intracellular ROS, promotes DNA damage and apoptosis in triple negative breast cancer cells. Journal of Ethnopharmacology, 332, 118389. https://doi.org/10.1016/j.jep.2024.118389