Abstract

Dracaena cinnabari Balf.f. is a red resin endemic to Socotra Island, Yemen. Although there have been several reports on its therapeutic properties, information on its cytotoxicity and anticancer effects is very limited. This study utilized a bioassay-guided fractionation approach to determine the cytotoxic and apoptosis-inducing effects of D. cinnabari on human oral squamous cell carcinoma (OSCC). The cytotoxic effects of D. cinnabari crude extract were observed in a panel of OSCC cell lines and were most pronounced in H400. Only fractions DCc and DCd were active on H400 cells; subfractions DCc15 and DCd16 exhibited the greatest cytotoxicity against H400 cells and D. cinnabari inhibited cells proliferation in a time-dependent manner. This was achieved primarily via apoptosis where externalization of phospholipid phosphatidylserine was observed using DAPI/Annexin V fluorescence double staining mechanism studied through mitochondrial membrane potential assay cytochrome c enzyme-linked immunosorbent and caspases activities revealed depolarization of mitochondrial membrane potential (MMP) and significant activation of caspases 9 and 3/7, concomitant with S phase arrest. Apoptotic proteins array suggested that MMP was regulated by Bcl-2 proteins family as results demonstrated an upregulation of Bax, Bad, and Bid as well as downregulation of Bcl-2. Hence, D. cinnabari has the potential to be developed as an anticancer agent.

Highlights

  • Oral squamous cell carcinoma (OSCC) is the sixth common malignancy in the world [1], principally due to the widespread use of tobacco and alcohol [2]

  • Fractions were isolated which exhibited cytotoxic effects that were selective against malignant cells compared to normal cells and these effects were associated with the induction of apoptosis, a depolarization mitochondrial membrane potential, translocation of cytochrome c from mitochondria into cytosol in H400 cells, and the activation of caspase 9

  • The results demonstrated that D. cinnabari crude extract was cytotoxic towards all the six oral squamous cell carcinoma (OSCC) cell lines as the IC50 values ≤20 μg/mL

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Summary

Introduction

Oral squamous cell carcinoma (OSCC) is the sixth common malignancy in the world [1], principally due to the widespread use of tobacco and alcohol [2]. In the present study we have utilized a bioassayguided fractionation approach to evaluate the cytotoxic and apoptosis-inducing effects of D. cinnabari on OSCC cells. Fractions were isolated which exhibited cytotoxic effects that were selective against malignant cells compared to normal cells and these effects were associated with the induction of apoptosis, a depolarization mitochondrial membrane potential, translocation of cytochrome c from mitochondria into cytosol in H400 cells, and the activation of caspase 9. The apoptosis through modulation on mitochondrial integrity associated with Bcl-2 family proteins as well as cell cycle arrest. These data highlight the potential of D. cinnabari as an anticancer agent and provide a guide for future efforts to develop more potent anticancer drugs

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