para-Phenylenediamine-induces apoptosis via a pathway dependent on PTK-Ras-Raf-JNK activation but independent of the PI3K/Akt pathway in NRK-52E cells

Kasi,Reena  A.P.; Moi,Chye  Soi; Kien,Yip  Wai; Yian,Koh  Rhun; Chin,Ng  Wei; Yen,Ng  Khuen; Ponnudurai,Gnanajothy; Fong,Seow  Heng

doi:10.3892/mmr.2014.2979

para-Phenylenediamine-induces apoptosis via a pathway dependent on PTK-Ras-Raf-JNK activation but independent of the PI3K/Akt pathway in NRK-52E cells

Authors:
- Reena A.P. Kasi
- Chye Soi Moi
- Yip Wai Kien
- Koh Rhun Yian
- Ng Wei Chin
- Ng Khuen Yen
- Gnanajothy Ponnudurai
- Seow Heng Fong
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Affiliations: Department of Human Biology, Cells and Molecules, International Medical University, Kuala Lumpur 57000, Malaysia, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, Selangor 43400, Malaysia, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Sunway Campus, Bandar Sunway, Selangor 47500, Malaysia
Published online on: November 19, 2014 https://doi.org/10.3892/mmr.2014.2979
Pages: 2262-2268

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Abstract

para‑Phenylenediamine (p‑PD) is a potential carcinogen, and widely used in marketed hair dye formulations. In the present study, the role of the protein tyrosine kinase (PTK)/Ras/Raf/c‑Jun N‑terminal kinase (JNK) and phosphoinositide 3‑kinase (PI3k)/protein kinase B (Akt) pathways on the growth of NRK‑52E cells was investigated. The results demonstrated that p‑PD reduced cell viability in a dose‑dependent manner. The cell death due to apoptosis was confirmed by cell cycle analysis and an Annexin‑V‑fluorescein isothiocyanate binding assay. Subsequent to staining with 2',7'‑dichlorofluorescin diacetate, the treated cells demonstrated a significant increase in reactive oxygen species (ROS) generation compared with the controls. The effects of p‑PD on the signalling pathways were analysed by western blotting. p‑PD‑treated cells exhibited an upregulated phospho‑stress‑activated protein kinase/JNK protein expression level and downregulated Ras and Raf protein expression levels; however, Akt, Bcl‑2, Bcl‑XL and Bad protein expression levels were not significantly altered compared with the control. In conclusion, p‑PD induced apoptosis by a PTK/Ras/Raf/JNK‑dependent pathway and was independent of the PI3K/Akt pathway in NRK‑52E cells.

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