Cytotoxicity of Mahanimbine from Curry Leaves in Human Breast Cancer Cells (MCF-7) via Mitochondrial Apoptosis and Anti-Angiogenesis.

Yahya Hasan Hobani

doi:10.3390/molecules27030971

Abstract

Mahanimbine (MN) is a carbazole alkaloid present in the leaves of Murraya koenigii, which is an integral part of medicinal and culinary practices in Asia. In the present study, the anticancer, apoptotic and anti-invasive potential of MN has been delineated in vitro. Apoptosis cells determination was carried out utilizing the acridine orange/propidium iodide double fluorescence test. During treatment, caspase-3/7,-8, and-9 enzymes and mitochondrial membrane potentials (Δψm) were evaluated. Anti-invasive properties were tested utilizing a wound-healing scratch test. Protein and gene expression studies were used to measure Bax, Bcl2, MMP-2, and -9 levels. The results show that MN could induce apoptosis in MCF-7 cells at 14 µM concentration IC50. MN-induced mitochondria-mediated apoptosis, with loss in Δψm, regulation of Bcl2/Bax, and accumulation of ROS (p ≤ 0.05). Caspase-3/7 and -9 enzyme activity were detected in MCF-7 cells after 24 and 48 h of treatment with MN. The anti-invasive property of MN was shown by inhibition of wound healing at the dose-dependent level and significantly suppressed mRNA and protein expression on MMP-2 and -9 in MCF-7 cells treated with a sub-cytotoxic dose of MN. The overall results indicate MN is a potential therapeutic compound against breast cancer as an apoptosis inducer and anti-invasive agent.

Highlights

Academic Editors: AlessandraWith approximately 1.4 million cases identified each year, breast cancer is the most prevalent disease among women, and it is the most frequently diagnosed cancer with more than 2 million new cases in 2020 according to GLOBOCAN data [1]
According to the present data, it can be clearly seen that MN inhibits cancer cell growth through programmed cell death
In the presence of MN, MCF-7 cells went into apoptosis, producing cell death signals that controlled ∆ψm by downregulating Bcl2 and upregulating Bax

Summary

Introduction

Academic Editors: AlessandraWith approximately 1.4 million cases identified each year, breast cancer is the most prevalent disease among women, and it is the most frequently diagnosed cancer with more than 2 million new cases in 2020 according to GLOBOCAN data [1]. Breast cancer was responsible for 684,996 deaths worldwide, an age-adjusted mortality rate of 13.6 deaths per 100,000 people [3]. This prevalence of breast cancer is a severe public health concern [4]. Because of medications that can interfere with the multiple biological processes involved in cancer cell proliferation, cytotoxic chemotherapy for breast cancer has made significant progress in recent years [5,6]. The accumulated ROS can activate initiators and executioner caspases, lose mitochondrial membrane potential (∆ψm ), and release cytochrome c into the cytosol. All of these events lead to apoptosis [11].

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Conclusion