Screening of natural product libraries in MCF7 cell line reveals the pro-apoptotic properties of β tetralone

Abstract

Despite the exponential increase in research toward better treatment options for breast cancer patients, developing an effective drug with fewer side effects continues to remain a challenge. Natural compounds have emerged as a viable option and several drugs have been derived or inspired from them. In this study, we screened a library of natural compounds with diverse chemical structures against selected kinase proteins using in silico methods such as molecular docking and dynamics simulation. The best results were obtained between β tetralone and MDM2 E3 ubiquitin ligase protein. In vitro experiments such as cytotoxicity, scratch assays and flow cytometry analysis using an MCF7 cell line were performed to determine the anti-cancer potential of the compound. As the treatment resulted in cell death and apoptosis, β tetralone was screened in silico against anti-apoptotic targets where the best results were obtained between Bcl-w and β tetralone. This comprehensive study suggests that the anti-cancer activity of β tetralone is probably through the dual targeting of MDM2 E3 ubiquitin kinase and Bcl-w anti-apoptotic protein.

Communicated by Ramaswamy H. Sarma

Keywords:

• Breast cancer
• β tetralone
• kinase
• molecular docking
• molecular dynamics
• apoptosis

Acknowledgments

The authors would like to thank the Director, of MIT School of Bioengineering Sciences & Research for providing an optimized Supercomputer for performing molecular docking simulations studies and other infrastructure support. NS thanks MIT Art, Design and Technology University, Rajbaugh Campus, Loni Kalbhor, Pune for awarding a Ph.D. Research Fellowship.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

All data generated or analyzed during this study are included in this published article (and its Supplementary Information files).

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.