Cyclophilin D modulates cell death transition from early apoptosis to programmed necrosis induced by honokiol Corrigendum in /10.3892/ijo.2021.5212

Tian,Wei; Xu,Dong; Han,Weidong; He,Haifei; Cai,Hongke; Chen,Hailong; Zhou,Meiqi; Chen,Jiani; Deng,Yong-Chuan

doi:10.3892/ijo.2013.1863

Cyclophilin D modulates cell death transition from early apoptosis to programmed necrosis induced by honokiol

Corrigendum in: /10.3892/ijo.2021.5212

Authors:
- Wei Tian
- Dong Xu
- Weidong Han
- Haifei He
- Hongke Cai
- Hailong Chen
- Meiqi Zhou
- Jiani Chen
- Yong-Chuan Deng
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Affiliations: Department of Surgical Oncology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, P.R. China, Division of Stem Cell and Leukemia Research, City of Hope National Medical Center, City of Hope, Duarte, CA 91010, USA
Published online on: March 22, 2013 https://doi.org/10.3892/ijo.2013.1863
Pages: 1654-1663

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Abstract

Honokiol is a pharmacologically active small molecule with multifunctional antitumor effects. Although plenty of literature is available on honokiol-triggered apoptosis and programmed necrosis, few studies have investigated the potential existence of death mode transition from apoptosis to programmed necrosis. In the current study, we demonstrated that the necrotic cell population (PI-positive) gradually increased and the early-stage apoptotic cell population (PI-negative and AV-positive) decreased in a dose- and time-dependent manner following honokiol treatment. Furthermore, we demonstrated that these PI-positive cells were under necrotic cell death, since no late-apoptosis characteristics including conspicuous chromatin condensation or DNA ladder patterns were detected. These results demonstrated that cells suffered death mode transition from early-stage apoptosis to programmed necrosis with the increase of honokiol dose or treatment time. The protein expression of RIP3 markedly increased in parallel with HNK-triggered death mode transition, while the expression of RIP1 decreased. Cyclophilin D expression increased during cell death mode transition, and inhibition of cyclophilin D by cyclosporin A clearly blocked HNK-triggered programmed necrosis. These data indicated that honokiol-induced programmed necrosis and death mode transition are potentially RIP3‑dependent, cyclophilin D-regulated. Further results showed that blocked cyclophilin D by cyclosporin A inhibited HNK-induced necrosis, but did not affect HNK-induced RIP3 overexpression. This indicated that cyclophilin D was a potential modulator at downstream of RIP3. In conclusion, honokiol triggers a potential RIP3-dependent cell death mode transition from early-stage apoptosis to programmed necrosis, which is highly regulated by cyclophilin D.

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