Soft Coral-Derived Dihydrosinularin Exhibits Antiproliferative Effects Associated with Apoptosis and DNA Damage in Oral Cancer Cells

Abstract

Dihydrosinularin (DHS) is an analog of soft coral-derived sinularin; however, the anticancer effects and mechanisms of DHS have seldom been reported. This investigation examined the antiproliferation ability and mechanisms of DHS on oral cancer cells. In a cell viability assay, DHS showed growth inhibition against several types of oral cancer cell lines (Ca9-22, SCC-9, OECM-1, CAL 27, OC-2, and HSC-3) with no cytotoxic side effects on non-malignant oral cells (HGF-1). Ca9-22 and SCC-9 cell lines showing high susceptibility to DHS were selected to explore the antiproliferation mechanisms of DHS. DHS also causes apoptosis as detected by annexin V, pancaspase, and caspase 3 activation. DHS induces oxidative stress, leading to the generation of reactive oxygen species (ROS)/mitochondrial superoxide (MitoSOX) and mitochondrial membrane potential (MitoMP) depletion. DHS also induced DNA damage by probing γH2AX phosphorylation. Pretreatment with the ROS scavenger N-acetylcysteine (NAC) can partly counter these DHS-induced changes. We report that the marine natural product DHS can inhibit the cell growth of oral cancer cells. Exploring the mechanisms of this cancer cell growth inhibition, we demonstrate the prominent role DHS plays in oxidative stress.

Advances in Small Molecular Agents against Oral Cancer

“…Sinularin (48) exerts oxidative stress-mediated anti-proliferative, G2/M-blocking, and apoptotic effects on OCC and is associated with ROS production, making it a potential marine drug against oral cancer [82]. Yang et al [83] confirmed that dihydrosinularin (49) exerts its anti-proliferative effect on OCC by inducing apoptosis, double-strand breaks, and DNA oxidative damage without causing cytotoxicity to non-malignant oral cells. Trichodermin (50) inhibits the migration and invasion of OSCC Ca922 and HSC-3 cells by down-regulating the expression of MMP-9.…”

Using nanotechnology to progress the utilization of marine natural products in combating multidrug resistance in cancer: A prospective strategy

“…In this study, DHS was first time reported to possess antiproliferative activity against cancer cells with no toxicity on noncancerous cells. [68] Gastropods are a class of invertebrates from the phylum Mollusca. 1).…”

“…[150] (4) The other mechanisms such as DNA damage due to some genetic changes, cell death inhibition using proapoptotic markers, or drug inactivation by various metabolic changes cause the drug to accumulate inside the cells to induce cytotoxic activity. [68] Recent research has shown that using targeted nanomedicines to deliver treatments directly to tumor cells can be an efficient strategy with reduced side effects of anticancer medications. [163] Three different natural sources of lecithin were used to make chitosancoated nanoliposomes containing CUR.…”

Boesenbergia stenophylla-Derived Stenophyllol B Exerts Antiproliferative and Oxidative Stress Responses in Triple-Negative Breast Cancer Cells with Few Side Effects in Normal Cells

“…Three types of oxidative stress biomarkers were assessed, including ROS, MitoSOX, and MMP. According to the user's manual, their matched probes, such as 2 ,7 -dichlorodihydrofluorescein diacetate (H 2 DCFDA) [46] (Sigma-Aldrich), MitoSOX™ Red [47] (Thermo Fisher Scientific, Carlsbad, CA, USA), and DiOC 2 (3) (Invitrogen, San Diego, CA, USA) [48], were chosen to detect the ROS, MitoSOX, and MMP, respectively. After the oxidative stress reaction, these probes become fluorescent molecules.…”