Cancer and apoptosis: The apoptotic activity of plant and marine natural products and their potential as targeted cancer therapeutics

Abstract

Cancer is a multifactorial, multi-stage disease, including complex cascades of signaling pathways-the cell growth governed by dysregulated and abrupt cell division. Due to the complexity and multi-regulatory cancer progression, cancer is still a challenging disease to treat and survive. The screening of extracts and fractions from plants and marine species might lead to the discovery of more effective compounds for cancer therapeutics. The isolated compounds and reformed analogs were known as future prospective contenders for anti-cancer chemotherapy. For example, Taxol, a potent mitotic inhibitor discovered from Taxus brevifolia, suppresses cell growth and arrest, induces apoptosis, and inhibits proliferation. Similarly, marine sponges show remarkable tumor chemo preventive and chemotherapeutic potential. However, there is limited research to date. Several plants and marine-derived anti-cancer compounds having the property to induce apoptosis have been approved for clinical trials. The anti-cancer activity kills the cell and slows the growth of cancer cells. Among cell death mechanisms, apoptosis induction is a more profound mechanism of cell death triggered by naturally isolated anti-cancer agents. Evading apoptosis is the major hurdle in killing cancer cells, a mechanism mainly regulated as intrinsic and extrinsic. However, it is possible to modify the apoptosis-resistant phenotype of the cell by altering many of these mechanisms. Various extracts and fractions successfully induce apoptosis, cell-cycle modulation, apoptosis, and anti-proliferative activity. Therefore, there is a pressing need to develop new anti-cancer drugs of natural origins to reduce the effects on normal cells. Here, we've emphasized the most critical elements: i) A better understanding of cancer progression and development and its origins, ii) Molecular strategies to inhibit the cell proliferation/Carcino-genesis, iii) Critical regulators of cancer cell proliferation and development, iv) Signaling Pathways in Apoptosis: Potential Targets for targeted therapeutics, v) Why Apoptosis induction is mandatory for effective chemotherapy, vi) Plants extracts/fractions as potential apoptotic inducers, vii) Marine extracts as Apoptotic inducers, viii) Marine isolated Targeted compounds as Apoptotic inducers (FDA Approved/treatment Phase). This study provides a potential therapeutic option for cancer, although more clinical studies are needed to verify its efficacy in cancer chemotherapy.

Keywords: apoptosis; apoptotic inducers; cancer; marine drug; natural product; targeted therapeutic.

FIGURE 1

The process of cancer development/carcinogenesis, (A) Cancer initiation (B). Cancer Progression (C). Metastasis and Cancer development. Created with BioRender.com.

FIGURE 2

Targeting regulators in inhibition of cell progression. It is mainly divided into apoptosis regulators and others. Targeting Apoptosis includes i) up-regulation of pro-apoptotic (caspases protein, Bax, and pro-apoptotic member of Bcl-2 family) ii) down-regulation of anti-apoptotic proteins (IAPs). Also, by targeting the pro-survival signaling pathways, invasion and metastasis proteins dysregulated in cancer cells, created with BioRender.com.

FIGURE 3

Apoptosis pathways. Apoptosis has two primary routes known as the i) extrinsic and ii) intrinsic pathway. First, external stimuli or ligand molecules activate the transduction, including death receptors (SDRs), leading to caspase 3/7 activation via/or activated caspase 8. Intrinsic pathway; via insertion of proapoptotic molecules BAX (protein) into the mitochondrial membrane results in the generation of cytochrome c, forming an apoptosome, which further triggers the apoptotic cascades beginning with proapoptotic activation caspase 9 and or then caspase 3. Created with BioRender.com.