Chemical analogues of a molecule obtained from a marine source prove to be effective against lung cancer

A team of Andalusian scientists from the Biosanitary Research Institute of Granada (ibs.GRANADA), the University of Granada (UGR) and the University of Málaga (UMA) have developed, based on the known structure of bengamide, chemical analogues that have demonstrated to be highly effective in human lung cancer cells and in tumors generated from these cells in mice. Furthermore, some of the derivatives have managed to be very effective in drug-resistant tumor cells, one of the main causes of chemotherapy failure, in this and other types of tumors, compounds that are currently in a patent process. . These studies have been developed in recent years through the achievement of different competitive projects that have allowed the collaboration of the Research Group led by Drs. José Carlos Prados and Consolación Melguizo of the Group A01-Technology Applied to Oncology and Gene Therapy from ibs.GRANADA and the Groups led by Drs. Juan Manuel López-Romero and Dr. Francisco Sarabia, both from the Department of Organic Chemistry of the UMA.

Lung cancer is among the three most frequently diagnosed cancers in the world and in our country. Its most common type, the so-called non-small cell lung cancer (NSCLC), has progressively increased its incidence and mortality in recent years despite advances in diagnostic and therapeutic methods. It is necessary to develop new therapeutic strategies that, applied, either individually or in combination with other therapies (surgical resection, chemotherapy, radiation, immunotherapy, etc.), help improve the survival rate of patients, especially those with a poor prognosis. most unfavorable. Among the main causes of this poor prognosis is the development of resistance to the medications commonly used in this pathology.

Bengamides are natural molecules described for the first time in marine sponges (family Jaspidae) for which a varied biological activity has been documented, including their antitumor capacity. This has led different research groups to study its mechanism of action and develop eco-sustainable analogues that improve its activity, reduce its side effects and even have new applications. In this context, the groups led by Drs. Juan Manuel López-Romero and Francisco Sarabia have used an alternative and improved synthesis of bengamide analogues that has made it possible to obtain the so-called Bengamide II and another molecule. The in vitro and in vivo studies carried out in the laboratories of Drs. José Carlos Prados and Consolación Melguizo have demonstrated for the first time that the synthesized Bengamida II is especially effective in lung cancer tumor cells, significantly inhibiting cell proliferation in systems in vitro 2D, reducing their capacity to form colonies, and in 3D systems, reducing the growth of multicellular spheroids (MTS) through systems such as autophagy and apoptosis mediated by caspase-3 activation. Furthermore, this molecule significantly reduced factors involved in angiogenesis, a key process in the development of tumor metastases. In vivo studies have corroborated the activity of bengamide II on tumors derived from lung cancer cells, in which it managed to significantly reduce the volume and generation of metastases, increasing the survival of the mice. One of the most relevant data was that, unlike other compounds and in the experiences carried out to date, no systemic or hematological toxic effects were observed at the doses used. However, more research will be necessary to expand our knowledge about its activity. On the other hand, the new analogue, which includes a modification of the general structure of Bengamide II, is currently under patent and has proven to be effective in cells that are characterized by being resistant to other antitumor agents.

The results of this line of work have given rise to a patent in the development phase by ibs.GRANADA, the UGR and the UMA and a publication in the prestigious journal Biomedicine and Pharmacotherapy.

About the research group:

The Technology Applied to Oncology and Gene Therapy research group at ibs.GRANADA, led by José Carlos Prados, has been consolidated over recent years thanks to the continuous expansion of its research staff and training staff. Its objective in recent years has focused on the development of new strategies for the treatment of cancer at an experimental level but with a purpose of clinical application, including the application of nanotechnological systems, the study of cancer stem cells, their resistance mechanisms. and its relevance as a target for new therapies, the determination of new molecules/extracts of plant origin with therapeutic or preventive capacity against cancer and the development of anti-tumor gene therapy systems. In addition, this group develops cancer diagnostic systems based on new technologies, including the determination of gene, protein and metabolomics-based markers, and works on aspects related to regenerative biomedicine, especially in the nervous and musculoskeletal systems.

More information about the group at https://www.ibsgranada.es/grupos-de-investigacion/a01-tecnologia-aplicada-a-oncologia-y-terapia-genica/

Bibliographic reference

Ortigosa-Palomo A, Porras-Alcalá C, Quiñonero F, Moya-Utrera F, Ortiz R, López-Romero JM, Melguizo C, Sarabia F, Prados J. Antitumor activity of bengamide II in a panel of human and murine tumor cell lines : In vitro and in vivo determination of effectiveness against lung cancer. Biomed Pharmacother. 2023 Dec;168:115789. doi: 10.1016/j.biopha.2023.115789.

Image: The research team from ibs.GRANADA and the UGR JC Prados, R. Ortiz, C. Melguizo, A. Ortigosa-Palomo, F. Quiñonero and (from left to right)