Novel natural product discovery from obligate symbiotic organisms of marine sponges

A rich source for the discovery of novel, pharmacologically active natural products has been terrestrial plants and microbes, accounting for about 85% of the approved natural products in pharmaceutical use (1), and about 60% of approved pharmaceuticals and new drug applications annually (2). Discovery in the marine environment has lagged due to the difficulty of exploration in this ecological niche. Such exploration began in the 1950’s, after technological advances such as scuba diving allowed collection of marine organisms, primarily to a depth of about 15m, which was the limit of that technology.Natural products from filter feeding marine invertebrates and in particular, sponges, have proven to be a rich source of structurally unique pharmacologically active compounds, with over 16,000 molecules isolated thus far (3, 1) and a continuing pace of discovery at hundreds of novel bioactive molecules per year. All classes of pharmaceuticals have been represented in this discovery process, including antiprotozoals, pesticides, TGF-beta inhibitors, cationic channel blockers, anticancer, cytotoxic, antiviral, anti-inflammatory and antibacterial compounds. Important biosynthetic pathways found in sponges which give rise to these compounds include the terpenoid (4), fatty acid, polyketoid, quinone reductase, alkaloid, isoprenoid (5), and non-ribosomal protein synthase pathways.

Cancer chemoprevention with natural agents: Where we are now?

Chemoprevention is defined as a means of cancer control in which the occurrence of clinical cancer can be prevented, slowed or reversed by the administration of one or more synthetic or naturally occurring biologic compounds [1-5]. In contrast to cancer treatment, the goal of chemoprevention is to reduce the incidence of clinical cancer. Preventing the onset of clinical cancer is desirable because therapy for established cancer is not uniformly effective. Chemoprevention also implies the prevention of precancerous lesions, which are called pre-invasive neoplasia, dysplasia, or intraepithelial neoplasia, depending on the organ system [5, 6]. The process of carcinogenesis involves the accumulation of multiple sequential genetic alterations and mutations that transforms a normal cell to a malignant cell capable of stromal invasion and ultimately metastasis. Carcinogenesis is traditionally separated into three phases: initiation, promotion and progression [6]. The initiation stage is relatively rapid and involves carcinogen binding and damage to DNA. The promotion phase is reversible, as tumor promoters act as mitogens to induce clones of initiated cells to expand. The promotion phase is a consequence of the functional loss of regulatory proteins and cellular checkpoints important for cellular proliferation and apoptosis. Progression is a stage in which phenotypically and genotypically altered cells develop irreversible macroscopic and microscopic changes. Because initiation and progression are irreversible, the promotion phase of carcinogenesis may be the best target for chemoprevention.