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Updated: Aug 5, 2026
Induction of Eryptosis in Red Blood Cells Using a Calcium Ionophore
Published on: January 21, 2020
Tasisulam-induced suicidal death of human erythrocytes
Abdulla Al Mamun Bhuyan1,2, Md Ashraf Zaman Faruk3, Md Niamot Ali1
1Department of Veterinary and Animal Sciences, University of Rajshahi, Bangladesh.
Abstract:
Tasisulam, an acyl-sulfonamide compound, is being investigated in clinical trials for the treatment of several malignancies, including non-small cell lung cancer, lymphoma, breast cancer, melanoma, ovarian cancer, colon cancer, and other solid tumors, by promoting apoptosis. However, anemia is among the adverse consequences of tasisulam therapy and is potentially caused by increased eryptosis or premature erythrocyte senescence, characterized by cell contraction and phosphatidylserine (PS) translocation. Underlying signals associated with eryptosis include increased intercellular calcium activity ([Ca2+]i), oxidative stress, excess ceramide production, and stimulation of various kinases (protein kinase C, p38 kinase, casein kinase-1, etc.) or caspases. This research investigated the potential of tasisulam to induce eryptosis and its underlying signaling pathways. Human erythrocytes (0.4%) were incubated with 75, 150, or 300 μg/ml tasisulam for 48 h at 37°C. Flow cytometry revealed that tasisulam (≥300 μg/ml) significantly increased erythrocyte apoptosis, [Ca2+]i, reactive oxygen species (ROS), and ceramide formation without causing cell membrane shrinkage. The effect of tasisulam on erythrocyte death was significantly reduced by the removal of extracellular calcium or the inhibition of casein kinase. In conclusion, tasisulam triggers eryptosis by stimulating calcium influx, ceramide generation, oxidative stress, and casein kinase 1 activation, which may be associated with tasisulam-associated anemia.
Insights
Tasisulam, an anti-cancer drug, may cause anemia by inducing eryptosis, a form of red blood cell death. This occurs through increased calcium, oxidative stress, and ceramide production, linked to casein kinase 1 activation.
Area of Science:
- Oncology
- Hematology
- Cell Biology
Background:
- Tasisulam, an acyl-sulfonamide, is under clinical investigation for various cancers.
- Anemia is a noted adverse effect of tasisulam, potentially linked to eryptosis (premature erythrocyte senescence).
- Eryptosis involves cell contraction, phosphatidylserine translocation, and is associated with increased intracellular calcium, oxidative stress, and ceramide.
Purpose of the Study:
- To investigate tasisulam's potential to induce eryptosis in human erythrocytes.
- To elucidate the underlying signaling pathways involved in tasisulam-induced eryptosis.
Main Methods:
- Human erythrocytes were incubated with varying concentrations of tasisulam (75, 150, 300 μg/ml) for 48 hours.
- Flow cytometry was used to assess erythrocyte apoptosis, intracellular calcium ([Ca2+]i), reactive oxygen species (ROS), and ceramide formation.
- The impact of extracellular calcium removal and casein kinase inhibition on tasisulam's effects was evaluated.
Main Results:
- Tasisulam (≥300 μg/ml) significantly increased erythrocyte apoptosis, [Ca2+]i, ROS, and ceramide formation.
- Cell membrane shrinkage was not observed, differentiating it from typical eryptosis.
- Eryptosis induction by tasisulam was significantly attenuated by removing extracellular calcium or inhibiting casein kinase.
Conclusions:
- Tasisulam induces eryptosis in human erythrocytes.
- The mechanism involves calcium influx, ceramide generation, oxidative stress, and casein kinase 1 activation.
- These findings suggest a potential mechanism for tasisulam-associated anemia.
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