Carbazole alkaloids from Murraya koenigii trigger apoptosis and autophagic flux inhibition in human oral squamous cell carcinoma cells

In this study, we investigated the anticancer properties and mechanisms of action of two carbazole alkaloids derived fromM. koenigii leaves, mahanine and isomahanine, in the OSCC cell line CLS-354. At 15  μM, mahanine and isomahanine were cytotoxic to CLS-354 cells, triggering apoptosis via caspase-dependent and -independent mechanisms. Autophagosomes, visualised using monodansylcadaverine (MDC) labelling, were numerous in carbazole alkaloid-treated cells. Mahanine and isomahanine markedly induced the expression of the autophagosome marker microtubule-associated protein 1 light chain 3, type II (LC3B-II). Genetic and chemical inhibition of autophagy via silencing of theAutophagy protein 5 gene and exposure to bafilomycin A1 (BafA1), respectively, did not arrest carbazole alkaloid-induced apoptosis, indicating that it occurs independently of autophagic activation. Surprisingly, both carbazole alkaloids caused increased accumulation of p62/sequestosome1 (p62/SQSTM1), with coordinated expression of LC3B-II and cleaved caspase-3, suggesting inhibition of autophagic flux. Our results suggest that inhibition of autophagic flux is associated with carbazole alkaloid-induced apoptosis. Our findings provide evidence of a novel cytotoxic action of natural carbazole alkaloids and support their use as candidate chemotherapeutic agents for the treatment of OSCC.
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research

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Conclusions: Surgery for elderly patients with LA-OCSCC is associated with a significant survival benefit, but the association is nonsignificant in the oldest elderly patients. No survival differences were observed between RT alone and CCRT in these elderly patients. Non-treatment should not be an option for these patients.
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research
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Source: Journal of Cancer Research and Clinical Oncology - Category: Cancer & Oncology Source Type: research
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Source: Journal of Oncology - Category: Cancer & Oncology Tags: J Oncol Source Type: research
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Source: Medical Oncology - Category: Cancer & Oncology Source Type: research
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Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Head and Neck Cancers Source Type: research
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Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Head and Neck Cancers Source Type: research
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Source: European Journal of Cancer Prevention - Category: Cancer & Oncology Tags: Oral Cancer Source Type: research
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Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research
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Source: The British Journal of Oral and Maxillofacial Surgery - Category: ENT & OMF Authors: Tags: 25 Source Type: research
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Source: International Journal of Oncology - Category: Cancer & Oncology Authors: Tags: Int J Oncol Source Type: research
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