**Madumani Amararathna 1, David W. Hoskin 2,3 and H. P. Vasantha Rupasinghe 1,2,\***


#### Academic Editor: Fabio Sonvico

Received: 26 July 2020; Accepted: 21 August 2020; Published: 22 August 2020

**Abstract:** In our previous study, we demonstrated that cyanidin-3-*O*-glucoside (C3G)-rich haskap (*Lonicera caerulea* L.) berry extracts can attenuate the carcinogen-induced DNA damage in normal lung epithelial cells *in vitro*. Here, the efficacy of lyophilized powder of whole haskap berry (C3G-HB) in lowering tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, (NNK)-induced lung tumorigenesis in A/JCr mice was investigated. Three weeks after daily oral administration of C3G-HB (6 mg of C3G in 0.2 g of C3G-HB/mouse/day), lung tumors were initiated by a single intraperitoneal injection of NNK. Dietary C3G-HB supplementation was continued, and 22 weeks later, mice were euthanized. Lung tumors were visualized through positron emission tomography (PET) and magnetic resonance imaging (MRI) 19 weeks after NNK injection. Dietary supplementation of C3G-HB significantly reduced the NNK-induced lung tumor multiplicity and tumor area but did not affect tumor incidence. Immunohistochemical analysis showed reduced expression of proliferative cell nuclear antigen (PCNA) and Ki-67 in lung tissues. Therefore, C3G-HB has the potential to reduce the lung tumorigenesis, and to be used as a source for developing dietary supplements or nutraceuticals for reducing the risk of lung cancer among high-risk populations.

**Keywords:** anthocyanin; tobacco-specific nitrosamine; carcinogenesis; cell proliferation; cancer chemoprevention; lung cancer
