Effect of nicotine- and tar-removed cigarette smoke extract on cancer metastasis

Yuta Takahashi,Koujirou Yamamoto,Daisuke Nagano,Ayumu Nagamine,Takuya Araki,Hideaki Yashima,Kyoko Obayashi

doi:10.24198/idjp.v3i2.35909

Abstract

Cigarette smoking is known to impact the promotion of carcinogenesis and tumor metastasis. On the other hand, some components in smoke were found to have health-promoting effects, and cancer suppressor effects of components in tobacco smoke have attracted attention. Although some studies showed the cancer suppressive effect of cigarette smoke extract (CSE) in vitro study, the effect of CSE administration on cancer is controversial. In this study, we investigated the effect of CSE-administration on tumor metastasis in a spontaneous tumor metastasis model using B16-BL6 cells, which is more clinical conditions. C57BL/6NCr mice were subcutaneously inoculated B16-BL6 cells into the footpad of the right rear leg. CSE was intraperitoneally administrated for 28 days from the day of inoculation. At 2 weeks after inoculation, the primary focus was excised. Subsequently, survival days of the mice were recorded to determine the effect of CSE-administration on spontaneous metastasis. The effect of CSE, α, β-unsaturated ketones, and aldehydes on B16-BL6 cell invasiveness were confirmed by matrigel invasion assay. Survival days of mice injected with 100% CSE was significantly shortened than that of control. B16-BL6 cell invasiveness was accelerated by the treatment with 0.1% CSE and 3 μM of crotonaldehyde. Intraperitoneal CSE-administration may progress spontaneous metastasis of B16-BL6 cells via enhancement of B16-BL6 cell invasiveness. As the cause, we found that crotonaldehyde contained in CSE may enhance the invasion ability of cancer cells. To clarify the cancer-suppressing effect of tobacco components, the effect of crotonaldehyde-removed CSE on tumor should be assessed in detail. Keywords: cigarette smoke extract (CSE), metastasis, crotonaldehyde (CA), B16-BL6 mouse melanoma cells, invasion

Highlights

Cigarette smoking is widely known to impact the promotion of carcinogenesis and tumor metastasis in several cancer types [14]
We investigated the effect of cigarette smoke extract (CSE) on tumor metastasis a spontaneous tumor metastasis model in which B16-BL6 cells were seeded subcutaneously in the footpad and subsequently developed lung metastatic nodules, which is more clinical conditions and can rule out the effects of direct exposure of CSE to the primary organ of tumor cell engraftment
CSE exposure did not affect cancer cell proliferation as Hatai reported, CSE promoted cancer cell invasion, which was different from the report by Hatai et al These results suggested that the decrease in survival time by CSE may be due to an increase in invasion ability of B16-BL6 cells

Summary

Introduction

Cigarette smoking is widely known to impact the promotion of carcinogenesis and tumor metastasis in several cancer types [14]. In a study of cigarette smoke, cigarette smoke exposure was reported to increase lung metastasis and tumor volume in colon and pancreatic cancer cell lines in mice [13, 14]. Known as one of the causes of tobacco dependence, is known to impact tumor growth and progression [15, 16], and Nguyen et al reported that nicotine promotes the proliferation and migration of melanoma cell line by regulating PD-L1 expression via α9 nicotinic acetylcholine receptors [17]

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Results

Conclusion