Plumbagin-induced anticancer effects are associated with mitochondrial-encoded respiratory gene downregulation in oral squamous cell carcinoma. Issue 6 (November 2022)

• Record Type: Journal Article
• Authors: Ono, Takayuki; Ota, Akinobu; Kato, Mikako; Karnan, Sivasundaram; Hyodo, Toshinori; Rahman, Md Lutfur; Hasan, Muhammad Nazmul; Onda, Maho; Nishio, Yoshitomo; Matsuyama, Remi; Takigawa, Yukako; Kondo, Sayuri; Ito, Kunihiro; Furuhashi, Akifumi; Hayashi, Tomio; Konishi, Hiroyuki; Tsuzuki, Shinobu; Hosokawa, Yoshitaka; Kazaoka, Yoshiaki
• Is Part Of: Journal of oral and maxillofacial surgery, medicine, and pathology. Volume 34:Issue 6(2022)
• Page Start: 805
• Page End: 812
• Publication Date: 2022-11
• Subjects: Plumbagin -- Oral squamous cell carcinoma -- Apoptosis -- Mitochondria -- Anti-cancer drug; Mouth -- Surgery -- Periodicals; Face -- Surgery -- Periodicals; Maxilla -- Surgery -- Periodicals; Oral medicine -- Periodicals; Mouth -- Diseases -- Pathogenesis -- Periodicals; Surgery, Oral -- Periodicals; Oral Medicine -- Periodicals; Pathology, Oral -- Periodicals; Face -- Surgery; Maxilla -- Surgery; Mouth -- Diseases -- Pathogenesis; Mouth -- Surgery; Oral medicine; Electronic journals -- Sciences; Electronic journals -- Medicine; Periodicals; 617.522059
• DOI: 10.1016/j.ajoms.2022.04.006
• Languages: English
• ISSNs: 2212-5566

Abstract

Abstract: Objective: Plumbagin (PL) is a known quinoid (5-hydroxyl-2-methyl-1, 4-napthoquinone) initially isolated from the roots of Plumbago zeylanica L. It is reported to exert anti-proliferative effects in oral squamous cell carcinoma (OSCC) cells, suggesting that PL would be a promising therapeutic anti-cancer drug for OSCC; however, the molecular basis by which PL suppresses cell survival signaling is poorly understood. In this study, we conducted a comprehensive gene expression analysis to identify the molecular basis by which PL suppresses cell survival signaling. Methods: Human OSCC cell lines HSC-3 and SAS were used in this study. Comprehensive gene expression analysis was performed with an Agilent Whole Human Genome DNA microarray 4 × 44 format. Gene Set Enrichment Analysis was conducted to investigate the effect of PL on the oncogenic signaling pathway in the OSCC cells. Results: cDNA microarray and subsequent gene set enrichment analyses showed that PL readily downregulates oxidative phosphorylation, MYC-target genes, and MTORC signaling at 4 h after treatment in HSC-3 and SAS cells. Semi-quantitative PCR analysis showed that gene expression levels of mitochondrial (Mt)-encoded COX-2, COX-3, and ND1 genes are significantly lower in the PL-treated OSCC cells than those in the untreated cells. In addition, an ROS scavenger, NAC, reversed the PL-induced downregulation of expression of Mt-encoded genes. Accordingly, intracellular ATP levels significantly decreased after PL treatment. Conclusions: Collectively, PL downregulates both oxidative phosphorylation and oncogenic signatures and decreases the survival of OSCC cells, thus highlighting its application as a potent treatment for patients with OSCC.