AdipoRon: a possible drug for colorectal cancer prevention?

Abstract

Colorectal cancer (CRC) is in the third place of the most common cancers. Certain risk factors can increase the development of CRC, including diet and inheritance. Several studies have shown that there is a potential link between obesity and CRC. Adipose tissue is known to be a largest endocrine organ in the body, with the ability to produce various cytokines including adiponectin. Two types of adiponectin receptor, AdipoR1 and AdipoR2, have been detected in various cancer tissues such as CRC. There is mounting evidence that AdipoR1 signaling occurs mainly through 5′ AMP-activated protein kinase (AMPK) and adiponectin inhibits colorectal cancer cell growth via activation of AMPK, thereby suppression of the mammalian target of rapamycin (mTOR) pathway. Thus, adiponectin replacement-based therapies may represent a novel approach in CRC cell growth inhibition in early stages. AdipoRon is an adiponectin-like synthetic small molecule that activated both adiponectin receptors 1 and 2. We hypothesize that AdipoRon has antiproliferative effects of adiponectin and may suppress the CRC cell growth. With clarification of this drug's role in CRC, it can be used as chemoprevention in patients at risk of developing the disease.

Examining the Potential of Developing and Implementing Use of Adiponectin-Targeted Therapeutics for Metabolic and Cardiovascular Diseases

“…AdipoRON effectively improved insulin sensitivity and restored glucose homeostasis via the activation of AdipoR1-AMPK-PGC1α and AdipoR2-PPARα signaling pathways (162). AdipoRON treatment also mimicked adiponectin's established anti-diabetic effects (163) and ability to enhance cellular capacity for mitigating oxidative-stress (162,164), enhancing lipid/glucose oxidation in mitochondria (162,164), anti-inflammatory responses (162,(164)(165)(166)(167), lifeprolonging effect (162,163), anti-cancer effects (168,169), procell survival and anti-apoptotic effect (170,171), neuronal- (172,173), reno- (174,175), and cardio-/vascular-protective effects (165,(176)(177)(178)(179). However, exciting AdipoRON research in animal models has not been translated to establishment of a drug for human use and the search continues for additional small molecule AdipoR agonists which have little or no toxicity.…”

The prognostic and therapeutic role of hormones in colorectal cancer: a review

“…Adiponectin supplementation has shown promise in suppressing colorectal carcinogenesis, likely through the adiponectin stimulated protein kinase (AMPK) phosphorylation in both in vitro and animal studies [7,17,18]. AdipoRon, an APN-like synthetic molecule, which likely acts via the same pathway, has been shown to improve insulin resistance and glucose tolerance, but also has been shown to inhibit pancreatic cancer cell proliferation [19]. Its antiproliferative effects via the AdipoR1 and AdipoR2 receptors could be a potential chemoprevention therapy in CRC, although it still remains to be investigated [19].…”

“…AdipoRon, an APN-like synthetic molecule, which likely acts via the same pathway, has been shown to improve insulin resistance and glucose tolerance, but also has been shown to inhibit pancreatic cancer cell proliferation [19]. Its antiproliferative effects via the AdipoR1 and AdipoR2 receptors could be a potential chemoprevention therapy in CRC, although it still remains to be investigated [19].…”

AdipoRon and Other Adiponectin Receptor Agonists as Potential Candidates in Cancer Treatments

“…In addition, despite the fact that no study has directly investigated the effect of AdipoRon in colorectal cancer (CRC), Malih and Najafi proposed a hypothetical model in which Acrp30 and AdipoRon had a similar behavior in suppressing CRC cell growth, hinting at the employment of this synthetic compound in obesity-related CRC chemoprevention [ 56 ]. To corroborate this assumption, organoids from low-fat mice treated with AdipoRon exhibited a reduction in Lgr5+ cells, a well-known marker of long-lived cycling stem cells capable of driving intestinal cancer [ 57 ].…”