Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 1;31(1):68-72.
doi: 10.4062/biomolther.2022.127. Epub 2022 Nov 16.

MS-5, a Naphthalene Derivative, Induces Apoptosis in Human Pancreatic Cancer BxPC-3 Cells by Modulating Reactive Oxygen Species

Suman Giri  1 , Gyu Hwan Park  2 , Joon-Seok Choi  1 , Eunsook Ma  1 , Kyung-Soo Chun  3 , Sang Hoon Joo  1
Affiliations

MS-5, a Naphthalene Derivative, Induces Apoptosis in Human Pancreatic Cancer BxPC-3 Cells by Modulating Reactive Oxygen Species

Suman Giri et al. Biomol Ther (Seoul). .

Abstract

Pancreatic cancer is one of the most fatal cancers with a poor prognosis. Standard chemotherapies have proven largely ineffective because of their toxicity and the development of resistance. Therefore, there is an urgent need to develop novel therapies. In this study, we investigated the antitumor activity of MS-5, a naphthalene derivative, on BxPC-3, a human pancreatic cancer cell line. We observed that MS-5 was cytotoxic to BxPC-3 cells, as well as inhibited the growth of cells in a concentration- and time- dependent manner. Flow cytometry analysis revealed that the percentage of annexin V-positive cells increased after MS-5 treatment. We also observed cleavage of caspases and poly (ADP-ribose) polymerase, and downregulation of Bcl-xL protein. Flow cytometry analysis of intracellular levels of reactive oxygen species (ROS) and mitochondrial superoxide suggested that MS-5 induced the generation of mitochondrial superoxide while lowering the overall intracellular ROS levels. Thus, MS-5 may be potential candidate for pancreatic cancer treatment.

Keywords: Apoptosis; Pancreatic cancer; Reactive oxygen species.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Cytotoxicity of MS-5 in human pancreatic cancer BxPC-3 cells. (A) Chemical structure of MS-5. (B) BxPC-3 cell viability after MS-5 treatment (5, 10, or 15 µM) for 24, 48, and 72 h. ***p< 0.001 compared to control. (C) Microscopic morphology of BxPC-3 cells after MS-5 treatment of (0, 5, 10, or 15 µM) for 24 h (scale bar=200 µm). (D) Flow cytometry analysis of BxPC-3 cells after MS-5 treatment for 24 h after staining with annexin V and propidium iodide.
Fig. 2
Fig. 2
Cellular markers of apoptosis in BxPC-3 cells after treatment of MS-5. Cell lysates were prepared for western blot analysis after treatment with MS-5 (0, 5, 10, and 15 µM) for 24 h. (A) Caspases-3, -7, -8, -9, and PARP cleavage. (B) Bak, Bax, Bcl-2, Bcl-xL. β-actin was used as the loading control.
Fig. 3
Fig. 3
Cell cycle arrest in BxPC-3 cells after treatment with MS-5. Cells were treated with the indicated concentrations of MS-5 for 24 h. (A) Cell cycle distribution was analyzed by flow cytometry after staining with propidium iodide. (B) Western blot analysis of cyclins A, and E, CDK2, and p27. β-actin was used as the loading control.
Fig. 4
Fig. 4
Levels of total ROS and mitochondrial superoxide in BxPC-3 cells after MS-5 treatment. Cells treated with MS-5 (0, 5, 10, and 15 µM) for 24 h were subjected to flow cytometry analysis to measure the levels of total ROS (A) and mitochondrial superoxide (B). (C) Western blot analysis of cell lysates for SOD1, SOD2, and HO-1 expression. β-Actin was used as the loading control. *p<0.05, **p<0.01 and ***p<0.001 compared to control.
Fig. 5
Fig. 5
Schematic diagram showing the mechanism of action underlying MS-5-induced cytotoxicity in human pancreatic cancer BxPC-3 cells. MS-5 induces the apoptosis and G1 phase arrest of BxPC-3 cells through modulating the ROS-regulating enzymes and by modulating reactive oxygen species.
See this image and copyright information in PMC

References

    1. Ali H., Pamarthy R., Vallabhaneni M., Sarfraz S., Ali H., Rafique H. Pancreatic cancer incidence trends in the United States from 2000-2017: analysis of Surveillance, Epidemiology and End Results (SEER) database. F1000Res. 2021;10:529. doi: 10.12688/f1000research.54390.1.5e3e36784a6f4fa59c599af08b16254d - DOI - PMC - PubMed
    1. Bilinski T., Litwinska J., Blaszczynski M., Bajus A. Superoxide dismutase deficiency and the toxicity of the products of autooxidation of polyunsaturated fatty acids in yeast. Biochim. Biophys. Acta. 1989;1001:102–106. doi: 10.1016/0005-2760(89)90312-3. - DOI - PubMed
    1. Cabiscol E., Piulats E., Echave P., Herrero E., Ros J. Oxidative stress promotes specific protein damage in Saccharomyces cerevisiae. J. Biol. Chem. 2000;275:27393–27398. doi: 10.1016/S0021-9258(19)61523-1. - DOI - PubMed
    1. Che M., Wang R., Li X., Wang H. Y., Zheng X. F. S. Expanding roles of superoxide dismutases in cell regulation and cancer. Drug Discov. Today. 2016;21:143–149. doi: 10.1016/j.drudis.2015.10.001. - DOI - PMC - PubMed
    1. Chu I., Sun J., Arnaout A., Kahn H., Hanna W., Narod S., Sun P., Tan C. K., Hengst L., Slingerland J. p27 phosphorylation by Src regulates inhibition of cyclin E-Cdk2. Cell. 2007;128:281–294. doi: 10.1016/j.cell.2006.11.049. - DOI - PMC - PubMed