Oxidative Stress-Dependent Synergistic Antiproliferation, Apoptosis, and DNA Damage of Ultraviolet-C and Coral-Derived Sinularin Combined Treatment for Oral Cancer Cells

Abstract

Combined treatment is increasingly used to improve cancer therapy. Non-ionizing radiation ultraviolet-C (UVC) and sinularin, a coral Sinularia flexibilis-derived cembranolide, were separately reported to provide an antiproliferation function to some kinds of cancer cells. However, an antiproliferation function using the combined treatment of UVC/sinularin has not been investigated as yet. This study aimed to examine the combined antiproliferation function and explore the combination of UVC/sinularin in oral cancer cells compared to normal oral cells. Regarding cell viability, UVC/sinularin displays the synergistic and selective killing of two oral cancer cell lines, but remains non-effective for normal oral cell lines compared to treatments in terms of MTS and ATP assays. In tests using the flow cytometry, luminescence, and Western blotting methods, UVC/sinularin-treated oral cancer cells exhibited higher reactive oxygen species production, mitochondrial superoxide generation, mitochondrial membrane potential destruction, annexin V, pan-caspase, caspase 3/7, and cleaved-poly (ADP-ribose) polymerase expressions than that in normal oral cells. Accordingly, oxidative stress and apoptosis are highly induced in a combined UVC/sinularin treatment. Moreover, UVC/sinularin treatment provides higher G2/M arrest and γH2AX/8-hydroxyl-2′deoxyguanosine-detected DNA damages in oral cancer cells than in the separate treatments. A pretreatment can revert all of these changes of UVC/sinularin treatment with the antioxidant N-acetylcysteine. Taken together, UVC/sinularin acting upon oral cancer cells exhibits a synergistic and selective antiproliferation ability involving oxidative stress-dependent apoptosis and cellular DNA damage with low toxic side effects on normal oral cells.

Combined Treatment (Ultraviolet-C/Physapruin A) Enhances Antiproliferation and Oxidative-Stress-Associated Mechanism in Oral Cancer Cells

“…All cell culture media, sera, and antibiotics were obtained from Gibco (Grand Island, NY, USA). Ca9-22 and CAL 27 cells were maintained in Dulbecco’s Modified Eagle Medium (DMEM)/F12 at a 3:2 ratio, and SG cells were kept at a 4:1 ratio [ 16 ]. After seeding at 1.5, 1, and 1.5 × 10 5 /6 cm dish for Ca9-22, CAL 27, and SG cells, respectively, the cells were incubated overnight for UVC and/or PHA experiments, as indicated in figure legends.…”

“…Several natural products have been reported in combined treatment with radiotherapy [ 10 , 11 ] to alleviate resistance or adverse effects and improve cancer treatment [ 12 , 13 ]. In addition to ionizing radiation (X-rays), non-ionizing radiation such as ultraviolet-C (UVC) also exhibits antiproliferation effects on several cancer types, such as pancreatic [ 14 ], colon [ 15 ], oral [ 16 ], and glioblastoma multiforme [ 17 ] cancer cells. UVC was combined with several clinical drugs [ 18 , 19 ] and natural products [ 16 , 20 ] to demonstrate anticancer effects.…”

Cytotoxic Compounds from Alcyoniidae: An Overview of the Last 30 Years

“…Chen et al [98] also extracted a novel skeletal norhumulene (sinugibberoside) and six xeniaphyllane-derived compounds (Gibberosins N-S) from S. gibberosa. Gibberosin O (194) was found to display cytotoxicity toward HepG2 and A-549 cell lines with (IC 50 values of 18.7 and 19.5 mg/mL, respectively, whereas gibberosin Q (195) exhibited cytotoxicity exclusively toward A549 cells with (IC 50 value of 11.0 mg/mL.…”

“…In addition to these studies, Peng et al [195] researched the potential synergistic antiproliferation of the combined treatment of ultraviolet-C and sinularin (UVC/sinularin) in oral cancer cells. The results showed that UVC/sinularin synergistically and selectively inhibits cancer cells proliferation with low cytotoxicity on normal oral cells.…”

Withaferin a Triggers Apoptosis and DNA Damage in Bladder Cancer J82 Cells through Oxidative Stress

“…Similarly, mRNA and protein levels for CAT, SOD1, and HMOX1 genes were activated in UVC-irradiated mice [44]. UVC was also reported to induce ROS generation in oral cancer cells [35,45]. Oxidative stress also activates TXN, which is a target of NFE2L2 [46].…”