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Anti-proliferative and cytotoxic effects of Strychnos nux-vomica root extract on human multiple myeloma cell line -
Pasupuleti Sreenivasa Rao1, Madduri Ramanadham, Majeti Narasimha Vara Prasad
1Laboratory of Environmental Biotechnology, Department of Plant Sciences, University of Hyderabad, School of Life Sciences, Gachhibowli, Hyderabad, Andhra Pradesh 500 046, India. sraopasupuleti@yahoo.com
Abstract:
Multiple myeloma (MM) is an incurable hematological malignancy with high incidence in the elderly. The currently used chemotherapeutic drugs show severe side effects, dose-limiting toxicity and development of resistance. In search of novel plant derived anti-cancer agents, Strychnos nux-vomica L. (SN) root extract was screened using the human MM-cell line, RPMI 8226. SN-extract exhibited anti-proliferative activity in a dose and time dependent manner. The morphological assessment of SN-extract treated cells showed significant features associated with apoptosis. Cell cycle analysis using flow cytometry of cells stained with propidium iodide revealed accumulation of cells at sub-G(0)/G(1) phase. In addition, disruption of mitochondrial membrane potential and subsequent leakage of mitochondrial cytochrome c was observed in SN-extract treated myeloma cells. The anti-proliferative and cytotoxic activity could be due to the alkaloids strychnine and brucine, which have been identified by LC-mass spectral analysis of the SN-extract in comparison to the reference standards analyzed under identical conditions.
Insights
Strychnos nux-vomica root extract shows promise as a natural treatment for multiple myeloma (MM). This plant extract demonstrated anti-cancer effects by inducing apoptosis and cell cycle arrest in MM cells.
Area of Science:
- Pharmacology
- Oncology
- Natural Products Chemistry
Background:
- Multiple myeloma (MM) is an incurable blood cancer, often affecting the elderly.
- Current MM treatments have severe side effects, toxicity, and lead to drug resistance.
- Novel, safer anti-cancer agents are needed for MM therapy.
Purpose of the Study:
- To investigate the anti-cancer potential of Strychnos nux-vomica L. (SN) root extract against human multiple myeloma cells.
- To identify the active compounds responsible for the observed anti-myeloma effects.
Main Methods:
- Screening of SN root extract using the human MM-cell line RPMI 8226.
- Assessing anti-proliferative activity, morphological changes, and apoptosis induction.
- Flow cytometry for cell cycle analysis and mitochondrial membrane potential assessment.
- LC-mass spectral analysis to identify alkaloids like strychnine and brucine.
Main Results:
- SN root extract demonstrated dose- and time-dependent anti-proliferative activity against MM cells.
- Morphological analysis revealed significant apoptosis in treated cells.
- Cell cycle arrest at the sub-G(0)/G(1) phase was observed.
- Disruption of mitochondrial membrane potential and cytochrome c release occurred.
- Strychnine and brucine were identified as potential active alkaloids in the extract.
Conclusions:
- Strychnos nux-vomica root extract exhibits significant anti-myeloma activity.
- The extract induces apoptosis and cell cycle arrest in multiple myeloma cells.
- Alkaloids strychnine and brucine are likely responsible for the observed anti-cancer effects, suggesting potential for natural MM therapies.
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