Xanthorrhizol Induces Apoptosis Through ROS‐Mediated MAPK Activation in Human Oral Squamous Cell Carcinoma Cells and Inhibits DMBA‐Induced Oral Carcinogenesis in Hamsters

Abstract

Xanthorrhizol, a natural sesquiterpenoid compound isolated from Curcuma xanthorrhiza Roxb, has been known to inhibit the growth of human colon, breast, liver and cervical cancer cells. In this study, xanthorrhizol decreased cell viability, induced apoptosis and decreased the level of full-length PARP in SCC-15 oral squamous cell carcinoma (OSCC) cells. A decrease in cell viability and PARP degradation was not prevented by treatment with the caspase inhibitor Z-VAD-fmk in xanthorrhizol-treated cells. Xanthorrhizol treatment elevated intracellular Ca(2+) and ROS levels in SCC-15 cells. Treatment with a Ca(2+) chelator, EGTA/AM, did not affect xanthorrhizol- induced cytotoxicity, but cell viability was partly recovered by treatment with endogenous antioxidant, GSH, or hydroxy radical trapper, MCI-186. Furthermore, the viability of xanthorrhizol-treated SCC-15 cells was significantly restored by treatment with SB203580 and/or SP600125 but not significantly by PD98059 treatment. Xanthorrhizol-induced activation of p38 MAPK and JNK was blocked by MCI-186. Finally, xanthorrhizol suppressed the number of tumors in buccal pouches and increased the survival rate in hamsters treated with 7,12-dimethylbenz[a]anthracene. In conclusion, xanthorrhizol may induce caspase-independent apoptosis through ROS-mediated p38 MAPK and JNK activation in SCC-15 OSCC cells and prevent chemical-induced oral carcinogenesis. Therefore, xanthorrhizol seems to be a promising chemopreventive agent.

Cantharidin Induced Oral Squamous Cell Carcinoma Cell Apoptosis via the JNK-Regulated Mitochondria and Endoplasmic Reticulum Stress-Related Signaling Pathways

“…Although patients received dental consultation prior to the initiation of radiotherapy, it still produced serious oral cavity problems that affect life quality [36]. Natural compounds have been preclinically and clinically investigated to be the chemopreventive or therapeutic agents for oral cancer [35, 37, 38]. Blister beetles are insects of family Meloidae , which contains about 2500 species, divided among 120 genera and 4 subfamilies (Eleticinae, Meloinae, Nemognathinae, and Tetraonycinae) [39, 40].…”

Association of cancer metabolism-related proteins with oral carcinogenesis – indications for chemoprevention and metabolic sensitizing of oral squamous cell carcinoma?

“…Therefore, bioactive food components inducing apoptosis by ROS generation (Table 2) and other mechanisms play an emerging role in cancer therapy. According to other tumor entities several other natural compounds have been shown to activate ROS [58,61] in OSCC [77-81] and subsequent apoptosis in cancer cells and may therefore provide a clear rational to study them in further pre-clinical and clinical trials (Table 2). Moreover, phytochemicals [82] and vitamins have different hypoxia-inducible factor-1 (HIF-1) binding capacities (inhibitory activity: lycopene > curcumin > tocopherol > ascorbic acid) suggestive for their impact on the decrease in tumor hypoxia and antioxidative properties in normal tissue [83].…”

Antibacterial and NMR analysis of Curcuma xanthorrhiza extract and fractions

“…Its antitumor activity was higher than that of compound 2. However, compound 2 has been studied for a number of biological targets, notably for its antimicrobial [14][15][16][17][18] and anticancer [28][29][30][31][32][33][34][35][36] properties. In conclusion, this study has shown that the antibacterial capacity of C. xanthorrhiza is contained in the n-hexane fraction.…”