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Zerumbone induces G2/M cell cycle arrest and apoptosis via mitochondrial pathway in Jurkat cell line
Abstract:
This investigation determined the anticancer properties of zerumbone (ZER) on the human T-cell (Jurkat) line using the MTT assay, microscopic evaluations, flow cytometric analyses, and caspase activity estimations. The results showed that ZER is selectively cytotoxic to Jurkat cells in a dose and time-dependent manner with IC50 of 11.9 ± 0.2, 8.6 ± 0.5 and 5.4 ± 0.4 μg/mL at 24, 48 and 72 hours of treatment, respectively. ZER did not produce an adverse effect on normal human peripheral blood mononuclear cells (PBMC). ZER is not as cytotoxic as doxorubicin, which imposed an inhibitory effect on Jurkat cells with IC50 of 2.1 ± 0.2, 1.8 ± 0.15, 1.5 ± 0.07 μg/mL after 24, 48 and 72 hours treatment, respectively. ZER significantly (P < 0.05) arrested Jurkat cells at the G2/M phase of the cell cycle. The antiproliferative effect of ZER on Jurkat cells was through the apoptotic intrinsic pathway via the activation of caspase-3 and -9. The results showed that ZER can be further developed into a safe chemotherapeutic compound for the treatment of cancers, especially leukemia.
Insights
Zerumbone (ZER) shows selective anticancer properties against human T-cell leukemia, inducing apoptosis without harming normal cells. This natural compound demonstrates potential as a safe chemotherapeutic agent for leukemia treatment.
Area of Science:
- Pharmacology
- Cell Biology
- Natural Products Chemistry
Background:
- Leukemia, particularly T-cell leukemia, remains a significant health concern requiring novel therapeutic strategies.
- Natural compounds are increasingly explored for their potential anticancer activities and favorable safety profiles.
- Zerumbone (ZER), a sesquiterpene from Zingiber zerumbet, has demonstrated various biological activities, including anti-inflammatory and antioxidant effects.
Purpose of the Study:
- To investigate the anticancer properties of zerumbone (ZER) against the human T-cell (Jurkat) leukemia cell line.
- To evaluate the selective cytotoxicity of ZER towards cancer cells compared to normal cells.
- To elucidate the mechanism of action of ZER in inducing cancer cell death.
Main Methods:
- Cytotoxicity was assessed using the MTT assay.
- Cell cycle arrest was analyzed via flow cytometry.
- Apoptosis induction was confirmed by measuring caspase-3 and -9 activity.
- Microscopic evaluations were performed to observe morphological changes.
Main Results:
- ZER exhibited selective dose- and time-dependent cytotoxicity against Jurkat cells (IC50 values ranging from 5.4 to 11.9 μg/mL).
- ZER did not show adverse effects on normal human peripheral blood mononuclear cells (PBMC).
- ZER induced significant G2/M phase cell cycle arrest and apoptosis via the intrinsic pathway, evidenced by caspase-3 and -9 activation.
Conclusions:
- ZER possesses selective anticancer properties against Jurkat leukemia cells.
- ZER induces apoptosis and cell cycle arrest, suggesting a potential chemotherapeutic mechanism.
- ZER demonstrates a favorable safety profile, making it a promising candidate for further development as a leukemia treatment.
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