Production of Terretonin N and Butyrolactone I by Thermophilic Aspergillus terreus TM8 Promoted Apoptosis and Cell Death in Human Prostate and Ovarian Cancer Cells.

Ayman Ghfar,Sami Gabr,Ahmad Aqel,Mohamed Habila,Wahidah Al-Qahtani,Mohamed Shaaban,Marwa Diab,Mohammad Alfaifi,Mohammad El-Metwally,Bayan Aljumah,Nada Gabr,Serag Elbehairi

doi:10.3390/molecules26092816

Abstract

The anticancer activity of terretonin N (1) and butyrolactone I (2), obtained from the thermophilic fungus Aspergillus terreus TM8, was intensively studied against prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines. According to this study, both compounds showed potent cytotoxicity towards ovarian adenocarcinoma cells (SKOV3) with IC50 1.2 and 0.6 μg/mL, respectively. With respect to metastatic prostate cells (PC-3), the two compounds 1 and 2 showed a significantly promising cytotoxicity effect with IC50 of 7.4 and 4.5 μg/mL, respectively. The tested fungal metabolites showed higher rates of early and late apoptosis with little or no necrotic apoptotic pathway in all treated prostate adenocarcinoma (PC-3) and ovary adenocarcinoma (SKOV3) human cell lines, respectively. The results reported in this study confirmed the promising biological properties of terretonin N (1) and butyrolactone I (2) as anticancer agents via the induction of cellular apoptosis. However, further studies are needed to elucidate the molecular mechanism by which cellular apoptosis is induced in cancer cells.

Highlights

Despite the progress made in the field of cancer research, there is still a need to discover and develop anticancer therapeutic agents, representing the main target of numerous research groups worldwide, especially as cancer is responsible for millions of deaths across the whole world
SKOV3 than PC-3 cells (Figures 3 and 4). In both PC-3 and SKOV3 cancer cells, the results showed that the activity of the metabolites terretonin N and butyrolactone I against cancer proceeded only via the apoptotic pathway (Figures 3 and 4), whereas they had no necrotic effect against the progression of cancer cells
The results showed that the activity of the metabolites terretonin N and butyrolactone I against SKOV3 cells, more than PC-3 cancer cells, only proceeded via an apoptotic pathway

Summary

Introduction

Despite the progress made in the field of cancer research, there is still a need to discover and develop anticancer therapeutic agents, representing the main target of numerous research groups worldwide, especially as cancer is responsible for millions of deaths across the whole world. The latter is responsible for approximately 7.6 million deaths worldwide and this is expected to increase to 13.1 million by 2030 [1]. Structural diversity and complex molecular architectures represent key features of the natural products from fungi. Natural products identified and characterized from fungi, isolated from extreme habitats, are considered as promising lead compounds, e.g., in tumor therapy [9]

Methods

Results

Discussion

Conclusion