Abstract
Mukonal is an active member of carbazole alkaloids isolated from Murraya koenigii. It has been shown to possess remarkable biological and pharmacological activities including anticancer activity. Therefore, the aim of current investigation was to explore anti-breast cancer activity of mukonal and to explore the underlying mechanism. Results indicate that mukonal has potential to induce antiproliferative effects against MDA-MB-231 and SK-BR-3 cells with an IC50 of 7.5 µM. No significant toxicity of mukonal was observed in case of normal breast cells. The antiproliferative effects of mukonal were found to proceed via apoptosis, which was further supported by increased cleavage of PARP and caspase-3 and reduced expression of Bcl-2. Mukonal induced autophagic cells death in breast cancer cells as was evidenced by formation of autophagosomes and enhanced expressions of Beclin-1, LC3B-I and LC3B-II proteins. In vivo examination of anti-breast cancer property of mukonal indicated that it could potentially reduce tumor weight and volume in xenografted mice models. In conclusion, mukonal has a remarkable potential of inhibiting breast cancer via induction of apoptosis and autophagy. Mukonal also inhibited xenografted tumors models in a dose-dependent manner. Therefore, mukonal may prove lead molecule in breast cancer drug discovery and treatment provided further investigations are recommended.
Highlights
Breast cancer is the most frequent and devastating disease prevailing in females worldwide
Mukonal (molecule is an active member of carbazole alkaloids found in Murraya koenigii (Bhattacharyya and Chakraborty 1984)
Mukonal inhibited proliferation of breast cancer cells The proliferation rate of four different cancer breast cell lines (MDA-MB-231, CAMA-1, MDA-MB-436 and SK-BR-3) and a normal breast MB157 cell line was determined using MTT assay after treatment with variant Mukonal 0-640 μM)
Summary
Breast cancer is the most frequent and devastating disease prevailing in females worldwide. Besides recent advances and effective management, breast cancer remains major cause of cancer related deaths in females of age 20–60 years. Mukonal (molecule is an active member of carbazole alkaloids found in Murraya koenigii (Bhattacharyya and Chakraborty 1984) This molecule has shown significant antioxidant, antimicrobial and anticancer activity (Samanta et al 2017). Mukonal has been reported to show anticancer activities against different human cancer cell lines in vitro including laryngeal AMC-HN-8 cancer cells and nasopharyngeal CNE-1 carcinoma cells. It has shown a remarkable potential of autophagy initiation, apoptosis induction, modification of mitochondrial membrane potential, cell cycle arrest, blocking of MEK/ERK and PI3K/AKT signalling pathways (Li et al 2018; Guo et al 2019). Current investigation was designed to unveil the anti-breast cancer potential of mukonal along with its effects of autophagy and apoptosis induction
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