Cell Cycle Arrest and Apoptosis Induction via Modulation of Mitochondrial Integrity by Bcl-2 Family Members and Caspase Dependence in Dracaena cinnabari-Treated H400 Human Oral Squamous Cell Carcinoma

Abstract EN

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.