**1. Introduction**

Lung cancer is the most commonly diagnosed cancer (11.6% of all the cancers), and the leading cause of cancer deaths (18.4% of all cancer deaths) among both men and women worldwide. Among western populations, over 80% of lung cancer incidence is attributed to tobacco smoking [1]. Tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), is a known lung carcinogen that causes lung tumors in laboratory animals and is likely to cause lung cancer in humans [2,3]. In the lungs, NNK is converted into reactive electrophilic metabolites, which cause point mutations in critical genes that involve cellular functions. Hence, NNK can deregulate the cell cycle, apoptosis, and DNA damage repair [4–6]. NNK also activates cell growth and proliferation signaling cascades, such as extracellular signal-regulated kinase 1/2 (ERK1/2), mitogen-activated protein kinase (MAPK) [5], and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) [7], resulting in tumorigenesis.

Numerous *in vitro*, *in vivo,* and epidemiological studies, have reported the benefits of flavonoids and flavonoid-rich plant extracts in preventing or curing cancer, including lung cancer [8,9]. For example, oral administration of anthocyanin-rich pomegranate juice reduces lung tumorigenesis in mice by inhibiting ERK1/2 and PI3K/AKT [10]. Anthocyanin is also able to suppress MAPK, Wnt/β-catenin signaling, and induce apoptosis [11–13]. Haskap (*Lonicera caerulea* L.), also known as blue honeysuckle, is a berry fruit with abundant anthocyanin, particularly cyanidin-3-*O*-glucoside (C3G). Haskap berry has a higher antioxidant capacity than other common fruits [14,15]. Recent studies have demonstrated anti-inflammatory [16,17], antiarthritis [18], antiobesity [19], and antidiabetic [20] properties of haskap berry. We have demonstrated that C3G-rich haskap berry extract can reduce NNK acetate-induced DNA double-strand breaks and oxidative stress in healthy human bronchial epithelial (BEAS-2B) cells *in vitro* [21]. The objective of this study was to investigate the chemopreventive ability of lyophilized C3G-rich whole haskap berry powder (C3G-HB) against NNK-induced lung tumorigenesis in A/JCr mice. The number of tumors, tumor area, and proliferative markers were used as parameters to detect the chemopreventive ability of C3G-HB. We found that C3G-HB can suppress NNK-induced lung tumorigenesis *in vivo*.
