Abstract
Sex hormone-dependent cancers currently contribute to the high number of cancer-related deaths worldwide. The study and elucidation of the molecular mechanisms underlying the progression of these tumors was a double-edged sword, leading to the expansion and development of new treatment options, with the cost of triggering more aggressive, therapy resistant relapses. The interaction of androgen, estrogen and progesterone hormones with specific receptors (AR, ER, PR) has emerged as a key player in the development and progression of breast, ovarian, prostate and endometrium cancers. Sex hormone-dependent cancers share a common and rather unique carcinogenesis mechanism involving the active role of endogenous and exogenous sex hormones to maintain high mitotic rates and increased cell proliferation thus increasing the probability of aberrant gene occurrence and accumulation highly correlated with abnormal cell division and the occurrence of malignant phenotypes. Cancer related hormone therapy has evolved, currently being associated with the blockade of other signaling pathways often associated with carcinogenesis and tumor progression in cancers, with promising results. However, despite the established developments, there are still several shortcomings to be addressed. Triterpenes are natural occurring secondary metabolites biosynthesized by various pathways starting from squalene cyclization. Due to their versatile therapeutic potential, including the extensively researched antiproliferative effect, these compounds are most definitely a cornerstone in the research and development of new natural/semisynthetic anticancer therapies. The present work thoroughly describes the ongoing research related to the antitumor activity of triterpenes in sex hormone-dependent cancers. Also, the current review highlights both the biological activity of various triterpenoid compounds and their featured mechanisms of action correlated with important chemical structural features.
Highlights
Malignant diseases or cancers are the cause of a high number of deaths worldwide each year and are characterized by the abnormal, uncontrolled division of cells due to inherited or environmental genetic cellular changes
The receptors often involved in mechanisms that lead to cancer progression are estrogen receptors (ER) and androgen receptors (AR)
An excellent review has been published by Bishayee et al on the topic of triterpene use against breast cancer; briefly, the authors reviewed the main types of triterpenoids tested in vitro on various breast cancer cell lines with some of these classes being subjected to in vivo assessments [124]
Summary
Malignant diseases or cancers are the cause of a high number of deaths worldwide each year and are characterized by the abnormal, uncontrolled division of cells due to inherited or environmental genetic cellular changes. Approximately 30,000 triterpenic compounds have been identified and classified according to their chemical structure and properties; in terms of biological significance, the most important representatives are the pentacyclic oleanane-, ursane-, and lupane-derivatives [31] and the tetracyclic dammarane- and euphane-derivatives [32] The review highlighted two key aspects for the clinical use of lupane triterpenes; firstly, they exert chemopreventive effects against risk factors that might trigger malignant processes and, secondly, triterpenes act selectively on tumor cells, leaving healthy cells unharmed In addition to their antitumor activity, triterpenes show antioxidative and antiinflammatory properties which frequently accompany immune modulation [38,39,40]. An analogue of CDDO, cyano enone of methyl boswellate (CEMB), was synthesized by TABLE 1 | Triterpenoid compounds with reported in vitro antiproliferative activity
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