Benzo[f]indole-4,9-dione Derivatives Effectively Inhibit the Growth of Triple-Negative Breast Cancer.

Fabiana Sélos Guerra,Flaviana Rodrigues Fintelman Dias,Patricia Dias Fernandes,Anna Claudia Cunha

doi:10.3390/molecules26154414

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer with poor clinical outcome, and currently no effective targeted therapies are available. Indole compounds have been shown to have potential antitumor activity against various cancer cells. In the present study, we found that new four benzo[f]indole-4,9-dione derivatives reduce TNBC cell viability by reactive oxygen species (ROS) accumulation stress in vitro. Further analyses showed that LACBio1, LACBio2, LACBio3 and LACBio4 exert cytotoxic effects on MDA-MB 231 cancer cell line by inducing the intrinsic apoptosis pathway, activating caspase 9 and Bax/Bcl-2 pathway in vitro. These results provide evidence that these new four benzo[f]indole-4,9-dione derivatives could be potential therapeutic agents against TNBC by promoting ROS stress-mediated apoptosis through intrinsic-pathway caspase activation.

Highlights

Breast cancer is a heterogeneous disease with varied biological features and histology, and it is the second most common cause of cancer mortality in women worldwide [1,2].Triple-negative breast cancer (TNBC) is an aggressive subtype that frequently develops resistance to chemotherapy
We found that the four compounds studied were able to induce apoptosis in MDA-MB 231 cells through the activation of proapoptotic proteins and induce G2/M cell cycle arrest
Our studies suggest that these four benzo[f ]indole-4,9-dione derivatives are potential prototypes for the development of drugs for the treatment of TNBC

Summary

Introduction

Breast cancer is a heterogeneous disease with varied biological features and histology, and it is the second most common cause of cancer mortality in women worldwide [1,2]. Triple-negative breast cancer (TNBC) is an aggressive subtype that frequently develops resistance to chemotherapy. In this subtype, estrogen and progesterone receptors are not expressed and human epidermal growth factor receptor 2 is not overexpressed [3,4]. TNBC is correlated with poor prognosis, metastases, recurrence and high mortality rates despite systemic therapy [5]. Treating patients with TNBC remains clinically challenging. Quinones represent a class of natural and synthetic compounds that have many beneficial effects, including antifungal, antiprotozoal, antibacterial and anticancer activities [6,7]

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Conclusion