Abstract

Lobocrassin B, a natural cembrane-type compound isolated from the soft coral Lobophytum crassum, has been shown to have significant biological effects, including anticancer activity. As the most common cause of cancer mortality worldwide, lung cancer remains a major concern threatening human health. In the current study, we conducted in vitro experiments to demonstrate the inhibiting effect of Lobocrassin B on CL1-5 and H520 human lung cancer cells growth and to explore the underlying mechanisms, as well as in nude mice bearing CL1-5 tumor xenografts. Lobocrassin B exerted cytotoxic effects on lung cancer cells, as shown by decreasing cell viability, and inducing apoptosis, oxidative stress and mitochondrial dysfunction. In addition, the increased level of Bax, cleaved caspase-3, -9 and -8, and the suppression of Bcl-2 were observed in the Lobocrassin B treated cells. Moreover, in vivo assays verified the significance of these results, revealing that Lobocrassin B inhibited CL1-5 tumor xenograft growth and that inhibitory effects were accompanied by a marked increase in tumor cell apoptosis. In conclusion, the results suggested that Lobocrassin B could be a potential anticancer compound for its propensity to inhibit growth and induce apoptosis in human lung cancer cells.

Highlights

  • Lung cancer is one of the most common causes of cancer-related death worldwide

  • Lobocrassin B is a natural cembrane-type compound diterpenoid firstly isolated from the soft coral Lobophytum crassum in 2011 and has been shown to exhibit a wide variety of biological effects, such as anti-cancer and immunomodulatory activities [7,8]

  • Mitochondrial functions playcentral centralroles rolesin in activating apoptosis in mammalian functional impairment of mitochondria is associated to the loss of

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Summary

Introduction

Lung cancer is one of the most common causes of cancer-related death worldwide. Siegel et al. Estimated the mortality rate of lung cancer-related cases of 2017 in USA could be more than one-quarter (26%) of all cancer deaths [1]. Toll-like receptor (TLR) pathway, but significantly inhibit the product of superoxide anion among other cembrane-type derivatives. It was found to possess moderate cytotoxicity to certain (TLR) pathway, but significantly inhibit the product of superoxide anion among other cembrane-type cancer cells, including human leukemia and human hepatoma [7]. It was found to possess moderate cytotoxicity to certain cancer cells, including mechanisms of this anti-cancer effect by Lobocrassin B remain unknown. Have been conducted on the anticancer effects of Lobocrassin B against human lung cancer cells. We explore its its potential mechanisms underlying the induced cancer cell death.

Cytotoxic
Lobocrassin cytotoxicity in in CL1-5
The levels ofofreleased in the themedium mediumofoflobocrassin lobocrassin
Lobocrassin B Induces Apoptosis in CL1-5 and H520 Cells
Incubation forfor
A incubation with Lobocrassin
Effect of Lobocrassin
B CL-15 and
Lobocrassin growth of of CL1-5
Discussion
Cell Culture
Chemicals
MTT Cell Viability Assay
Caspase Inhibitor Assay
DNA Content by Flow Cytometric Analysis
Western Blot Analysis
4.10. Animals’ Experimentation
4.11. Tumor Xenograft Model
4.12. Statistical Analysis
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