Oral administration of kiwi fruit juice inhibited lung cancer in mice and reduced lung nodules

Lung cancer is the leading cause
of death in Japan and around the world.
Of all cancers, lung cancer has one of
the lowest five-year survival rates.
It is well known that smoking and the use of tobacco products largely contribute to the development of
lung cancer.
It is a clinically proven fact that the active ingredients in various fruits minimize the risk of
chronic diseases, including cancer.
"Sarunashi" (a soft date kiwi) is an edible fruit
grown in Okayama Prefecture, Japan.
Researchers at Okayama University, led by Dr.
Sakae Arimoto-Kobayashi, associate professor at Okayama University's Faculty of Pharmacy, used mouse models to demonstrate that Sarunashi juice and its component isoquercetin (isoQ) help prevent and reduce lung cancer
.

Kiwi fruit is one of the richest sources of polyphenols and vitamin C, and researchers have previously demonstrated the inhibitory effect
of Sarunashi juice on mutagenesis, inflammation, and skin tumors in mice.
As a water-soluble and heat-sensitive phenolic compound, it has an anti-mutagenic effect
.
Subsequently, the researchers proposed the polyphenolic compound isoQ as a component with anti-cancer potential
.

Dr.
Arimoto-Kobayashi explains, "In this study, we sought to investigate the preventive effect of Sarunashi juice and its constituent isoQ on 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanone (NNK)-induced A/J mouse lung tumors and identified the possible mechanisms
of Actinidia arguta's antitumor effects.

To do this, the team induced tumor growth in mice using NNK, a known carcinogenic compound
found in tobacco products.
Through a series of experiments and controls, the team studied the effects of
sar-j and isoQ on lung tumorigenesis in mice.

The results were encouraging: the number of tumor nodules per mouse lung in the group that received both NNK injections and oral NNK doses, in addition, oral isoQ also reduced the number of nodules in the lungs of
mice.

Next, the team discovered a possible mechanism of action, making a breakthrough
.
NNK and 1-methyl-3-nitro-1-nitrosoguanidine or "MNNG" are known mutagens – agents that trigger DNA mutations
.
Therefore, the team designed a series of experiments to study the effects
of sar-j and isoQ on NNK- and MNNG-mediated mutagenesis.

Salmonella typhimurium TA1535 is a strain
commonly used to detect DNA mutations.
The results showed that the mutagenicity of both NNK and MNNG was detected
.
In the presence of sar-j, TA1535 is lowered
.
However, when performed using a similar bacterial infection test, sar-j was unable to reduce the mutagenic effects
of NNK and MNNG due to YG7108's lack of key enzymes responsible for DNA repair.
Based on this key observation, the researchers concluded that sar-j appears to modulate its anti-mutational effects
by accelerating DNA repair.

Finally, through cell-based experiments, the team also showed that sar-j inhibited the action of "Akt," a key protein
involved in cancer signaling.
Akt and a related protein called "PI3k" are known to be overactivated
in several human cancers.

One of the authors, Professor of the Department of Allergy and Respiratory Medicine at Okayama University Hospital, mused, "Sar-j and isoQ reduced NNK-induced lung tumorigenesis
.
Sar-J targets initiation and growth or progression steps during cancer development, particularly by anti-mutation, stimulating alkyl DNA adduct repair, and inhibiting AKT-mediated growth signaling pathways
.
IsoQ may contribute to the biological effects of sar-j to some extent by inhibiting Akt phosphorylation, but it may not be the main active ingredient
.
”

Their findings were published December 9, 2022 in Genes and Environment
.
In conclusion, the study showed that oral administration of SAR-J inhibited the occurrence
of lung tumors in mice.
While clinical trials are needed, the constituent components of sar-J, including isoQ, appear to be attractive candidates for chemoprevention
.