Vanillin Differentially Affects Azoxymethane-Injected Rat Colon Carcinogenesis and Gene Expression

Abstract

Vanillin is the substance responsible for the flavor and smell of vanilla, a widely used flavoring agent. Previous studies reported that vanillin is a good antimutagen and anticarcinogen. However, there are also some contradicting findings showing that vanillin was a comutagen and cocarcinogen. This study investigated whether vanillin is an anticarcinogen or a cocarcinogen in rats induced with azoxymethane (AOM). Rats induced with AOM will develop aberrant crypt foci (ACF). AOM-challenged rats were treated with vanillin orally and intraperitoneally at low and high concentrations and ACF density, multiplicity, and distribution were observed. The gene expression of 14 colorectal cancer-related genes was also studied. Results showed that vanillin consumed orally had no effect on ACF. However, high concentrations (300 mg/kg body weight) of vanillin administered through intraperitoneal injection could increase ACF density and ACF multiplicity. ACF were mainly found in the distal colon rather than in the mid-section and proximal colon. The expression of colorectal cancer biomarkers, protooncogenes, recombinational repair, mismatch repair, and cell cycle arrest, and tumor suppressor gene expression were also affected by vanillin. Vanillin was not cocarcinogenic when consumed orally. However, it was cocarcinogenic when being administered intraperitoneally at high concentration. Hence, the use of vanillin in food should be safe but might have cocarcinogenic potential when it is used in high concentration for therapeutic purposes.

Overview of the Role of Vanillin on Redox Status and Cancer Development

“…Vanillin consumed orally had no effect on ACF; however, when administered through intraperitoneal injection at higher concentration vanillin was cocarcinogenic, which could well increase ACF density and multiplicity. The expression of colorectal cancer biomarkers, protooncogenes (beta-catenin↑ and FOS↑), recombinational repair (XRCC2↑), mismatch repair (PMS2↑), cell cycle arrest (p21↑ and cyclin B↓), and tumor suppressor gene (tumor suppressor gene p53↑) were also affected by vanillin [62, 63]. The mixed anticarcinogenic/cocarcinogenic results found for vanillin suggest that other carcinogen models must be evaluated to better understand the role of vanillin on carcinogenesis.…”

Modulation of NADPH oxidase and Nrf2/HO-1 pathway by vanillin in cisplatin-induced nephrotoxicity in rats

“…Vanillin ( 4‐Hydroxy‐3‐methoxybenzaldehyde ) is a natural nontoxic food flavour. [ 13 ] It possesses antioxidant and anti‐inflammatory activity in different CCl 4 ‐induced injuries such as acute liver injury, [ 14 ] nephrotoxicity, [ 15 ] oxidative brain injury [ 16 ] and erythrocyte oxidative damage. [ 17 ] Furthermore, vanillin was reported to possess multiorgan antineoplastic activity.…”

“…[ 17 ] Furthermore, vanillin was reported to possess multiorgan antineoplastic activity. [ 18,13,19 ] We reported antineoplastic activity of vanillin in vivo in mouse model of breast cancer and in MCF‐7 human breast cancer cell line. [ 20 ] Vanillin exerted antineoplastic effect similar to that of doxorubicin with improved survival and no side effects as seen in doxorubicin treatment.…”

Therapeutic role of vanillin receptors in cancer

“…100 Other studies have examined the effects of vanillin in rats with aberrant crypt foci (ACF) induced with azoxymethane. 101 In these studies, the animals were given vanillin at either a low or a high dose, and several parameters, such as ACF density and distribution, as well as gene expression, were monitored. Although orally delivered 4-hydroxy-3-methoxybenzaldehyde did not yield any significant results, vanillin administered through intraperitoneal injection (at the higher concentration) was cancerogenic.…”