Dr. Gautam Sethi E-Mail
Associate Professor, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Research Keywords: signal transduction; apoptosis; transcription factors; metastasis; mouse models of cancer
Transcription factors play an important role in regulating gene expression by binding to specific DNA sequences. However, once deregulated several transcription factors can mediate ontogenesis and mediate tumor initiation, promotion and progression. They can regulate a number of genes involved in abnormal proliferation, survival, angiogenesis, and metastasis of tumor cells. A number of pharmacological strategies have been employed to target the aberrant activation of transcription factors to control tumorigenesis. These include approaches to affect their expression, by mitigating protein/protein interactions, and by preventing their DNA binding at specific DNA-interacting sites. This special issue will highlight these strategies and the potential utility of these transcription factors as “druggable targets”.
Keywords: transcription factors; cancer; gene expression; apoptosis; small molecules
Cancer remains the second leading cause of mortality globally. In combating cancer, conventional chemotherapy and/or radiotherapy are administered as first-line therapy. However, these are usually accompanied with adverse side effects that decrease the quality of patient’s lives. As such, natural bioactive compounds have gained an attraction in the scientific and medical community as evidence of their anticancer properties and attenuation of side effects mounted. In particular, quassinoids have been found to exhibit a plethora of inhibitory activities such as anti-proliferative effects on tumor development and metastasis. Recently, bruceine D, a quassinoid isolated from the shrub Brucea javanica (L.) Merr. (Simaroubaceae), has come under immense investigation on its antineoplastic properties in various human cancers including pancreas, breast, lung, blood, bone, and liver. In this review, we have highlighted the antineoplastic effects of bruceine D and its mode of actions in different tumor models.
Tanshinone is a herbal medicinal compound described in Chinese medicine, extracted from the roots of Salvia miltiorrhiza (Danshen). This family of compounds, including Tanshinone IIA and Tanshinone I, have shown remarkable potential as anti-cancer molecules, especially against breast, cervical, colorectal, gastric, lung, and prostate cancer cell lines, as well as leukaemia, melanoma, and hepatocellular carcinoma among others. Recent data has indicated that Tanshinones can modulate multiple molecular pathways such as PI3K/Akt, MAPK and JAK/STAT3, and exert their pharmacological effects against different malignancies. In addition, preclinical and clinical data, together with the safety profile of Tanshinones, encourage further applications of these compounds in cancer therapeutics. In this review article, the effect of Tanshinones on different cancers, challenges in their pharmacological development, and opportunities to harness their clinical potential have been documented.