Cinobufacini, a substance extracted for venom glands of an Asian toad, has been a recognized therapy in traditional Chinese medicine for many years. Some of its major compounds, such as bufalin, have been shown to have significant anti-cancer activity, resulting in tumour shrinkage upon treatment.

Recent research reveals how bufalin exploits a range of different pathways to induce apoptosis – programmed cell death – of malignant cells and control the development of several cancers.

In a study published in BMC Complementary & Alternative Medicine, scientists demonstrate bufalin is an effective prostate cancer treatment, inducing apoptosis through non-coding microRNAs (miRNAs). These molecules are involved in transcriptional regulation of a large proportion of the genome, including major cell death regulators, such as Bcl-2 protein family. Abnormal miRNA activity has been shown to promote increased cell proliferation, invasion and angiogenesis and in the development of tumours. However, the study confirms significant correlation of bufalin treatment and upregulation of appropriate miRNAs with an increased apoptotic response, while miRNA inhibitors weaken bufalin-induced apoptosis.

Similar results were also achieved in a study in Tumour Biology based on pancreatic cancer. Malignant cells were shown to undergo cell cycle arrest in response to bufalin treatment in a dose-dependant manner. Expression of a number of genes was demonstrated to be affected by bufalin, including indirect effect on Bcl-2 family, as well as other proteins involved in apoptosis. Moreover, bufalin was shown to have a synergistic anti-cancer effect while in use with other anti-cancer treatments, such as chemotherapeutic gemcitabine, inhibiting the growth of pancreatic cancer cells significantly.

In a separate study in BMC Complementary & Alternative Medicine, bufalin was demonstrated to inhibit the proliferation and adhesion of hepatocellular carcinoma cells by influencing an important cell-cell adhesion protein β-catenin. Unbalanced expression of this molecule is associated with increased migration and invasion of carcinoma cells, causing a high rate of metastases. Bufalin was shown to influence β-catenin signalling pathway and stabilize gene expression, thus controlling the spread of the cancer.

Positive effect of bufalin has been demonstrated for other cancers as well, including gastric, ovarian cancers, lung adenocarcinoma and others, suggesting a promising anti-cancer treatment. Analysis of pathway of bufalin-induced control of cancer cells is a whole new pharmacological avenue and could lead to potent anti-tumour therapy in the near future.

Source: www.technology.org