AKT serine/threonine protein kinase modulates bufalin-triggered intrinsic pathway of apoptosis in CAL 27 human oral cancer cells

Abstract

Abstract. Bufalin has been reported to induce apoptosis in a variety of cancers but little is demonstrated in oral squamous cell carcinoma (OSCC) cells. The present study investigated the inhibition of proliferation, cell cycle arrest and apoptotic effects of bufalin in CAL 27 human oral cancer cells. Bufalin inhibited the growth of CAL 27 cells in a concentration-dependent manner and an IC 50 value of bufalin was about 125 nM for 24 h treatment using the MTT assay. Moreover, the cell cycle distribution was arrested at the G 0 /G 1 phase in CAL 27 cells after bufalin exposure. Upon bufalin stimulation, the expression of Bcl-2 was significantly decreased while that of cytochrome c, Apaf-1 and AIF was increased compared to the control group by western blot analysis. An increase in the expression of the active form of caspases was found in bufalin-treated cells, and the caspase activities were also elevated. Bufalin-triggered apoptosis was blocked by specific inhibitors of caspase-9 (z-LEHD-fmk) and caspase-3 (z-DEVD-fmk), respectively. In contrast, CAL 27 cells overexpressing constitutively active AKT (CAL 27/CA-AKT) were exposed to bufalin at different concentrations, and cell growth remained unchanged. Bufalin exhibited minimal apoptotic effects on CAL 27/CA-AKT cells. Taken together, bufalin induced G 0 /G 1 phase arrest and provoked the intrinsic apoptotic pathway via AKT activation in CAL 27 cells. Our data suggest that bufalin could be potentially efficacious in the treatment of oral cancer in the future.

Bufalin attenuates the stage and metastatic potential of hepatocellular carcinoma in nude mice

“…These results indicate a close relationship of the actions of bufalin in the inhibition of HCC growth and enhancement of necrosis and apoptosis in orthotopic-transplanted tumor tissue, which are related to regulation of the PI3K/Akt signaling pathway. Therefore, our results are consistent with those of previous studies showing that bufalin induces apoptosis in gastric cancer MGC803 cells and oral cancer CAL 27 cells by inhibition of the PI3K/AKT signaling pathway [10,11]. …”

“…In previous studies, bufalin has been demonstrated to induce apoptosis in gastric cancer MGC803 cells and oral cancer CAL 27 cells by inhibition of the AKT signaling pathway [10,11]. Our previous in vitro studies have shown that the mechanisms underlying the antitumor effects of bufalin in hepatoma cells appear to be mediated by AKT/GSK3β/β-catenin/E-cadherin signaling pathways [12].…”

Tetrandrine induces cell death in SAS human oral cancer cells through caspase activation-dependent apoptosis and LC3-I and LC3-II activation-dependent autophagy

“…The current treatments for oral cancer are inadequate and a significant proportion of oral cancer patients may develop local invasion and metastases (11). Numerous studies have been performed to find novel agents (especial from natural plant) which can trigger programmed cell death (apoptosis) in tumor cells and hopefully to provide a new therapeutic approach for anticancer design (12)(13)(14).…”

Immunoliposome co-delivery of bufalin and anti-CD40 antibody adjuvant induces synergetic therapeutic efficacy against melanoma

“…Bufalin has excellent antitumor effects against various solid tumors, including those associated with leukemia, osteosarcoma, gastric cancer, prostate cancer, ovarian cancer, and colon cancer. [1][2][3][4][5][6][7][8][9][10][11] Previous studies have suggested that the anticancer activity of bufalin could be attributed to its well-documented inhibition of cell proliferation, induction of apoptosis, disruption of the cell cycle, and regulation of the immune response. 12,13 Although these results are promising, the use of this single chemotherapeutic drug is far from perfected and is associated with undesirable severe side effects such as immunosuppression, damage to normal tissues, high toxicity, and development of drug resistance.…”