Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage

Thushara, R. M.; Hemshekhar, Mahadevappa; Sunitha, K.; Kumar, Manmohan; Naveen, S.; Kemparaju, K.; Girish, K. S.

doi:10.1016/j.biochi.2013.07.032

Cited by 30 publications

(27 citation statements)

References 35 publications

(40 reference statements)

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“…However, high dose (>50 mg/kg) of sesamol was also reported to cause hyperactivity in rats41. Besides, adequate studies suggested that sesamol induced cancer cell apoptosis at a dose range from 0.1 to 1 mM, yet there is one report indicated that a higher dose (>0.25 mM) of sesamol may induce blood platelets damage42. This potentially toxic effect highlights the critical need for proper dosage when sesamol is developed for clinical use.…”

Section: Discussionmentioning

confidence: 99%

Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy

Liu

Ren

Wang

et al. 2017

Sci Rep

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Sesamol, a nutritional phenolic antioxidant compound enriched in sesame seeds, has been shown to have potential anticancer activities. This study aims at characterizing the antitumor efficacy of sesamol and unveiling the importance of mitochondria in sesamol-induced effects using a human hepatocellular carcinoma cell line, HepG2 cells. Results of this study showed that sesamol treatment suppressed colony formation, elicited S phase arrest during cell cycle progression, and induced both intrinsic and extrinsic apoptotic pathway in vitro with a dose-dependent manner. Furthermore, sesamol treatment elicited mitochondrial dysfunction by inducing a loss of mitochondrial membrane potential. Impaired mitochondria and accumulated H2O2 production resulted in disturbance of redox-sensitive signaling including Akt and MAPKs pathways. Mitochondrial biogenesis was inhibited as suggested by the decline in expression of mitochondrial complex I subunit ND1, and the upstream AMPK/PGC1α signals. Importantly, sesamol inhibited mitophagy and autophagy through impeding the PI3K Class III/Belin-1 pathway. Autophagy stimulator rapamycin reversed sesamol-induced apoptosis and mitochondrial respiration disorders. Moreover, it was also shown that sesamol has potent anti-hepatoma activity in a xenograft nude mice model. These data suggest that mitochondria play an essential role in sesamol-induced HepG2 cells death, and further research targeting mitochondria will provide more chemotherapeutic opportunities.

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Section: Discussionmentioning

confidence: 99%

Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy

Liu

Ren

Wang

et al. 2017

Sci Rep

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“…40Res/2013-14), University of Mysore, Mysore. The drawn blood was immediately mixed with acid citrate dextrose (ACD) anticoagulant and processed as described previously to obtain platelet rich plasma (PRP) and washed platelets [21]. The cell count was determined in both PRP and washed platelet suspensions using a Neubauer chamber and adjusted to 5×10 8 cells/mL in the final suspension using platelet poor plasma/Tyrode’s albumin buffer (pH 7.4).…”

Section: Methodsmentioning

confidence: 99%

Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide

et al. 2015

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Thrombocytopenia in methotrexate (MTX)-treated cancer and rheumatoid arthritis (RA) patients connotes the interference of MTX with platelets. Hence, it seemed appealing to appraise the effect of MTX on platelets. Thereby, the mechanism of action of MTX on platelets was dissected. MTX (10 μM) induced activation of pro-apoptotic proteins Bid, Bax and Bad through JNK phosphorylation leading to ΔΨm dissipation, cytochrome c release and caspase activation, culminating in apoptosis. The use of specific inhibitor for JNK abrogates the MTX-induced activation of pro-apoptotic proteins and downstream events confirming JNK phosphorylation by MTX as a key event. We also demonstrate that platelet mitochondria as prime sources of ROS which plays a central role in MTX-induced apoptosis. Further, MTX induces oxidative stress by altering the levels of ROS and glutathione cycle. In parallel, the clinically approved thiol antioxidant N-acetylcysteine (NAC) and its derivative N-acetylcysteine amide (NACA) proficiently alleviate MTX-induced platelet apoptosis and oxidative damage. These findings underpin the dearth of research on interference of therapeutic drugs with platelets, despite their importance in human health and disease. Therefore, the use of antioxidants as supplementary therapy seems to be a safe bet in pathologies associated with altered platelet functions.

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“…The obtained platelet‐rich plasma (PRP) was centrifuged at 1700 g and washed twice with Citrate Glucose Saline (CGS) buffer (123 mM NaCl, 33 mM d ‐glucose, 13 mM Tri‐sodium citrate, pH 6.5) at 1700 g for 10 min at 37°C. Finally, washed platelets (WP's) were suspended in modified Tyrode's buffer (2.5 mM HEPES, 150 mM NaCl, 2.5 mM KCl, 12 mM NaHCO 3 , 1 mM CaCl 2 , 1 mM MgCl 2 , 5.5 mM d ‐glucose, 0.3% bovine serum albumin pH 7.4) and the cell count was adjusted to 5 × 10 8 cells/mL using Neubauer chamber …”

Section: Methodsmentioning

confidence: 99%

Para‐tertiary butyl catechol (PTBC), an industrial antioxidant induces human platelet apoptosis

Vishalakshi

NaveenKumar

Hemshekhar

et al. 2018

Environmental Toxicology

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The catecholic derivative para-tertiary butyl catechol (PTBC) is a conventional antioxidant and polymerization inhibitor, which exhibits melanocytotoxic effects and contact dermatitis often leading to occupational leucoderma or vitiligo. Although numerous industrial workers will be in constant exposure to PTBC and its chances of getting entry into blood are most expected, its effect on blood components is still undisclosed. As platelets play a prominent role in dermatitis, inflammation, and immunity, in this study we have evaluated the effect of PTBC on human platelets in vitro. Exposure of platelets to PTBC showed increased reactive oxygen species (ROS), intracellular calcium, cardiolipin oxidation, mitochondrial permeability transition pore (MPTP) formation, activation of caspases, phosphatidylserine (PS) externalization and decreased mitochondrial membrane potential. In addition, there was a significant decrease in cellular glutathione level, increased γ-glutamyltransferase (GGT) activity and cell death. These findings demonstrate that PTBC could induce toxic effects on blood components, which is often ignored field of research. Since dermal exposure of humans to toxic chemicals covers an important issue in various industries, there is a need of such work to understand and update the long-term toxicities induced by PTBC usage in industrial sectors and public domain. K E Y W O R D S apoptosis, mitochondria, oxidative stress, platelets, PTBC

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Sesamol induces apoptosis in human platelets via reactive oxygen species-mediated mitochondrial damage

Cited by 30 publications

References 35 publications

Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy

Sesamol Induces Human Hepatocellular Carcinoma Cells Apoptosis by Impairing Mitochondrial Function and Suppressing Autophagy

Methotrexate Promotes Platelet Apoptosis via JNK-Mediated Mitochondrial Damage: Alleviation by N-Acetylcysteine and N-Acetylcysteine Amide

Para‐tertiary butyl catechol (PTBC), an industrial antioxidant induces human platelet apoptosis

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