Sulforaphane regulates cell proliferation and induces apoptotic cell death mediated by ROS-cell cycle arrest in pancreatic cancer cells

Yongmin Cho; Moon Nyeo Park; Min Choi; Tarun Kumar Upadhyay; Han Na Kang; Jeong Min Oh; Soonki Min; Ji-Ung Yang; Moonkyoo Kong; Seong-Gyu Ko; Md Ataur Rahman; Abdel Halim Harrath; Bonglee Kim

doi:10.3389/fonc.2024.1442737

Sulforaphane regulates cell proliferation and induces apoptotic cell death mediated by ROS-cell cycle arrest in pancreatic cancer cells

Front Oncol. 2024 Aug 29:14:1442737. doi: 10.3389/fonc.2024.1442737. eCollection 2024.

Authors

Yongmin Cho¹, Moon Nyeo Park^{1

2}, Min Choi^{1

2}, Tarun Kumar Upadhyay³, Han Na Kang⁴, Jeong Min Oh¹, Soonki Min⁵, Ji-Ung Yang⁵, Moonkyoo Kong⁵, Seong-Gyu Ko², Md Ataur Rahman⁶, Abdel Halim Harrath⁷, Bonglee Kim^{1

2}

Affiliations

¹ Department of Pathology, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
² Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.
³ Department of Biotechnology, Parul Institute of Applied Sciences and Research and Development Cell, Parul University, Vadodara, Gujarat, India.
⁴ KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea.
⁵ Division of Lung and Head and Neck Oncology, Department of Radiation Oncology, Kyung Hee University Medical Center, Kyung Hee University College of Medicine, Seoul, Republic of Korea.
⁶ Department of Neurology, University of Michigan, Ann Arbor, MI, United States.
⁷ Department of Zoology, College of Science, King Saud University, Riyadh, Saudi Arabia.

Abstract

Background: Pancreatic cancer (PC), sometimes referred to as pancreatic ductal adenocarcinoma (PDAC), is a major cause of global mortality from cancer. Pancreatic cancer is a very aggressive and devastating kind of cancer, characterized by limited options for therapy and low possibilities of survival. Sulforaphane (SFN), a naturally occurring sulfur-containing compound, is believed to possess anti-inflammatory, anti-obesity, and anti-cancer characteristics.

Objective: However, efficient preventative and treatment measures are essential and SFN has been studied for its ability to suppress pancreatic cancer cell proliferation and induce apoptosis.

Methods: Here, SFN induced cytotoxicity and apoptosis in PDAC cell lines such as MIA PaCa-2 and PANC-1 cells, as evaluated by cytotoxicity, colony formation, western blot analysis, fluorescence-activated cell sorting (FACS), reactive oxygen species (ROS) detection, caspase-3 activity assay, immunofluorescence assay, and mitochondrial membrane potential assay.

Results: In MIA PaCa-2 and PANC-1 cells, SFN inhibited cell survival and proliferation in a dose-dependent manner. The activation of caspase zymogens results in cleaved PARP and cleaved caspase-3, which is associated with an accumulation in the sub G1 phase. Furthermore, SFN increased ROS level and γH2A.X expression while decreasing mitochondrial membrane potential (ΔΨm). Notably, the ROS scavenger N-Acetyl-L-cysteine (NAC) was shown to reverse SFN-induced cytotoxicity and ROS level. Subsequently, SFN-induced cell cycle arrest and apoptosis induction as a Trojan horse to eliminate pancreatic cancer cells via ROS-mediated pathways were used to inhibit pancreatic cancer cells.

Conclusion: Collectively, our data demonstrates that SFN-induced cell death follows the apoptosis pathway, making it a viable target for therapeutic interventions against pancreatic cancer.

Keywords: apoptosis; mitochondrial membrane potential (ΔΨm); pancreatic cancer; reactive oxygen species (ROS); sub G1; sulforaphane (SFN); γH2A.X.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2020R1I1A2066868), the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2020R1A5A2019413), Basic Science Research Program through the National Research Foundation of Korea(NRF) grant funded by the Korea government(MSIT)(RS-2024-00350362), and the National Research Foundation of Korea. grant numbers: 2021R1C1C2014229. The authors extend their appreciation to Researchers Supporting Project number RSP2024R17, King Saud University, Riyadh, Saudi Arabia.