Abstract
The induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies. Bufalin is a cardiotonic steroid that has the potential to induce differentiation and apoptosis of tumor cells. Research on bufalin has so far mainly involved leukemia, prostate cancer, gastric cancer and liver cancer, and has been confined to in vitro studies. The bufadienolides bufalin and cinobufagin have been shown to induce apoptosis in a wide spectrum of cancer cell. The present article reviews the anticancer effects of bufalin. It induces apoptosis of lung cancer cells via the PI3K/Akt pathway and also suppressed the proliferation of human non-small cell lung cancer A549 cell line in a time and dose dependent manner. Bufalin, bufotalin and gamabufotalin, key bufadienolides, significantly sensitize human breast cancer cells with differing ER-alpha status to apoptosis induction by the TNF-related apoptosis-inducing ligand (TRAIL). In addition, bufadienolides induce prostate cancer cell apoptosis more significantly than that in breast epithelial cell lines. Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear. Bufalin exerts profound effects on leukemia therapy in vitro. Results of multiple studies indicate that bufalin has marked anti-tumor activities through its ability to induce apoptosis. Large-scale randomized, double-blind, placebo or positive drug parallel controlled studies are now required to confirm the efficacy and apoptosis-inducing potential of bufalin in various cancers in the cliniucal setting.
Highlights
It’s been 50 years since chemotherapy was introduced into the clinical practice of cancer treatment
Similar effects have been observed with hepatocellular carcinoma (HCC) but the detailed molecular mechanisms of inducing apoptosis in this case are still unclear
Recent observations suggest that the induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies, including chemotherapy, γ-radiation, immunotherapy, and cytokines (Kaufmann et al, 2000)
Summary
It’s been 50 years since chemotherapy was introduced into the clinical practice of cancer treatment. Chemotherapy has been successful in the treatment of some forms of cancer; it is not the case for the majority of epithelial tumors of the breast, colon, lung, and ovary. Many observations have indicated that cell death plays a significant role during physiological processes of multicellular organisms, during embryogenesis and metamorphosis (Gluecksmann et al, 1951; Lockshin et al, 2001). The molecular mechanisms of apoptosis and its function in normal physiology are crucial in understanding the effect of chemotherapy and the mechanisms of chemoresistance. Recent observations suggest that the induction of apoptosis in target cells is a key mechanism for most anti-tumor therapies, including chemotherapy, γ-radiation, immunotherapy, and cytokines (Kaufmann et al, 2000). In this review article we have reviewed the anticancer properties of Bufalin from the perspective of an emerging treatment option for cancer patients
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