Apoptosis Induced by Tarantula cubensis Crude Venom (Theranekron® D6) in Cancer Cells

Natural compounds from venomous animals have a big potent in cancer drug discovery. This study aimed to investigate the apoptotic potential of Theranekron D6, an alcoholic extract of the venom from the whole spider Tarantula cubensis , in cells derived from breast (MCF-7), lung (A549), and bone (Saos-2) cancer. TD6 stimulated a significant increase in the oxidative stress and stimulated apoptosis in cancer cells. To understand the molecular mechanism for the induction of cell death by TD6, fluorometric apoptosis/necrosis and RT-PCR assays were performed. In MCF-7 cell line, TD6 increased CAS-9 expression, as well as the mRNA and protein expression ratio of BAX/BCL-2. Furthermore, protein expression level of the Pro-CAS-9 was decreased in TD6-treated MCF-7 cells. TD6 increased CAS-9 and CAS-3 expressions in A549 and Saos-2 cell lines, but the expression ratio of the BAX/BCL-2 did not increase at the gene transcription level in these cancer cell lines. Moreover, the protein level of BAX/BCL-2 ratio was increased in TD6-treated Saos-2 cells, and the Pro-CAS-3 and Pro-CAS-9 were down-regulated in Saos-2 and A549 cell lines. Therefore, Theranekron D6 could be an excellent alternative therapeutic drug for the treatment of malignant neoplasm as an apoptosis inducer agent. Graphical abstract