Potential of apoptotic pathway-targeted cancer therapeutic research: Where do we stand?

Abstract

Underneath the intricacy of every cancer lies mysterious events that impel the tumour cell and its posterity into abnormal growth and tissue invasion. Oncogenic mutations disturb the regulatory circuits responsible for the governance of versatile cellular functions, permitting tumour cells to endure deregulated proliferation, resist to proapoptotic insults, invade and erode normal tissues and above all escape apoptosis. This disruption of apoptosis has been highly implicated in various malignancies and has been exploited as an anticancer strategy. Owing to the fact that apoptosis causes minimal inflammation and damage to the tissue, apoptotic cell death-based therapy has been the centre of attraction for the development of anticancer drugs. Increased understanding of the molecular pathways underlying apoptosis has enabled scientists to establish unique approaches targeting apoptosis pathways in cancer therapeutics. In this review, we reconnoitre the two major pathways (intrinsic and extrinsic) targeted cancer therapeutics, steering toward chief modulators of these pathways, such as B-cell lymphoma 2 protein family members (pro- and antiapoptotic), inhibitor of apoptosis proteins, and the foremost thespian of extrinsic pathway regulator, tumour necrosis factor-related apoptosis-inducing agent. Together, we also will have a look from clinical perspective to address the agents (drugs) and therapeutic strategies adopted to target these specific proteins/pathways that have entered clinical trials.

Extracellular NAMPT/Visfatin induces proliferation through ERK1/2 and AKT and inhibits apoptosis in breast cancer cells

“…Many cancer treatment strategies rely on induction of apoptosis and its inhibition renders cells resistant to diverse apoptotic stimuli [52]. Thus inhibition of apoptosis by visfatin as well as its influence on survivin, may be responsible for the poor prognosis which accompanies increased visfatin levels in breast cancer patients.…”

Mitochondrial ribosomes in cancer

“…Hence, over the past decade, a promising cancer therapeutic strategy has been targeting anti-apoptotic proteins that will restore the apoptotic pathway. Because none of the three mitoribosomal proteins shown to possess a role in apoptosis induction (mS29, mL41 and mL65) has been so far directly targeted for therapeutics, we refer the reader interested in the targeting of apoptosis pathways for cancer treatment to several extensive reviews published elsewhere [138–140]. …”

Hesperidin‐CAMKIV interaction and its impact on cell proliferation and apoptosis in the human hepatic carcinoma and neuroblastoma cells

“…A significant decrease in the viability of HepG2 and SH-SY5Y cells was observed with increase in hesperidin concentration (Figure 3). The IC 50 (concentration at which 50% inhibition in cell growth was observed) values of hesperidin against the studied cell lines were determined from the plot of percentage cell viability versus hesperidin concentration. The IC 50 of hesperidin for HepG2 and SH-SY5Y were found to be 47 μM and 75 μM, respectively.…”

“…Hesperidin treatment induces apoptosis in the HepG2 cells. On increasing the concentration of hesperidin (25,50, and 75 µM), a significant increase in the apoptotic cells (8.1%, 13.4%, and 30.3%, respectively) was observed ( Figure 4A), and maximum apoptosis (30.3%) was achieved at 75 μM. A comparable result was also found in the case of SH-SY5Y cells where the proportion of apoptotic cells were 7.8%, 12.6%, and 27.4%, at 25, 50 and 75 μM concentration of hesperidin, respectively ( Figure 4B).…”