Combined chemotherapy and ALA-based photodynamic therapy in leukemic murine cells

Towards Novel Anti-tumor Strategies for Hepatic Cancer: ɛ-Viniferin in Combination with Vincristine Displays Pharmacodynamic Synergy at Lower Doses in HepG2 Cells

“…Therefore, there is an urgent need for the development of a new agent or newer combination, yet chemotherapy remains crucial to the treatment of hepatocellular cancer through inducing apoptotic signaling system. The vinca alkaloid anticancer drug, vincristine, is an effective chemotherapeutic agent that is extensively used for the treatment of many malignancies (Eing-Ju et al, 1995;Steiner et al, 1983) such as leukemia (Diez et al, 2012), breast (Casado et al, 2007), retinoblastoma (Conway et al, 1998), and hepatoma (Sun et al, 2009) cancer cells. Vincristine exerts its anticancer effect by binding to the building blocks of microtubules.…”

“…In this way, vincristine stops the separation of the duplicated chromosomes and induces G2/M phase arrest (Meininger et al, 1990), c-Jun NH 2 -terminal kinase activation (Wang et al, 1998), Bcl-2 phosphorylation (Ruvolo et al, 2001), and apoptosis (Wang et al, 1998). However, in the clinical situation, neurotoxicity (Legha, 1986) and drug resistance effects (Diez et al, 2012;Koike et al, 1997;Sun et al, 2009) of vincristine have been reported and the neurotoxicity of vincristine can present serious clinical problems. Therefore, in the present study a combination of vincristine and e-viniferin, which is a derivative of transresveratrol, was investigated to develop new therapeutic strategies that are efficient and less toxic to the treatment of hepatocellular cancer.…”

“…Recently, a few studies have shown that combining treatment with vincristine and other agents such as adriamycin, cyclophosphamide in the treatment of children with malignant hepatoma (Evans et al, 1982), and doxorubicin in the treatment of (Diez et al, 2012), showed lower cytotoxicity and drug resistance as well as better therapeutic efficiacy. However, as far as we know, no studies about the apoptotic effects of vincristine combined with e-viniferin in HepG2 cells have been reported.…”

“…All this data showed that the addition of e-viniferin might modulate HepG2 cells sensitive to vincristine at low concentrations. Some studies have shown that treatment of a combination of vincristine with doxorubicin in murine leukemic cells (Diez, et al, 2012) or estradiol in MCF7 cells (Martinez-Campa et al, 2006) inhibited cell growth and sensitized cells to vincristine in vitro. Increased sensitivity of HepG2 cells to vincristine was also confirmed by the enhanced vincristine-induced apoptosis in the presence of e-viniferin.…”

“…This data indicated that treatment with e-viniferin and vincristine inhibited HepG2 cell viability by inducing early apoptosis and significant early apoptotic activity could be achieved by combined treatment with e-viniferin and vincristine. Vincristine induces apoptosis (Ruvolo et al, 2001;Wang et al, 1998) in various cells, such as breast cancer cells (Casada et al, 2007;Martinez-Compa et al, 2006), retinoblastoma (Conway et al, 1998), and leukemia cells (Diez et al, 2012) in vitro. In addition, vincristine regulates the phosphorylation of the anti-apoptotic protein HSP27 in breast cancer cells (Casado et al, 2007).…”