2. Academic Validation
  3. Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells

Urolithin A induces cell cycle arrest and apoptosis by inhibiting Bcl-2, increasing p53-p21 proteins and reactive oxygen species production in colorectal cancer cells

  • Cell Stress Chaperones. 2021 May;26(3):473-493. doi: 10.1007/s12192-020-01189-8.
Mohammad S El-Wetidy  # 1 2,  Rehan Ahmad  # 3,  Islam Rady 1 4,  Hamed Helal 1,  Mohamad I Rady 1,  Mansoor-Ali Vaali-Mohammed 5,  Khayal Al-Khayal 5,  Thamer Bin Traiki 5,  Maha-Hamadien Abdulla 6
Affiliations

Affiliations

  • 1 Zoology Department, Faculty of Science, Al-Azhar University, Nasr City, Cairo, 11823, Egypt.
  • 2 College of Medicine Research Center, King Saud University, Riyadh, 11461, Kingdom of Saudi Arabia.
  • 3 Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia. arehan@ksu.edu.sa.
  • 4 Department of Dermatology, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, 53706, USA.
  • 5 Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia.
  • 6 Colorectal Research Chair, Department of Surgery, College of Medicine, King Saud University, PO Box 7805 (37), Riyadh, 11472, Kingdom of Saudi Arabia. mabdulla@ksu.edu.sa.
  • # Contributed equally.
PMID: 33666815 DOI: 10.1007/s12192-020-01189-8
Abstract

Colorectal Cancer (CRC) is the second most common gastrointestinal Cancer globally. Prevention of tumor cell proliferation and metastasis is vital for prolonging patient survival. Polyphenols provide a wide range of health benefits and prevention from Cancer. In the gut, urolithins are the major metabolites of Polyphenols. The objective of our study was to elucidate the molecular mechanism of the Anticancer effect of urolithin A (UA) on colorectal Cancer cells. UA was found to inhibit the cell proliferation of CRC cell lines in a dose-dependent and time-dependent manner in HT29, SW480, and SW620 cells. Exposure to UA resulted in cell cycle arrest in a dose-dependent manner along with alteration in the expression of cell cycle-related protein. Treatment of CRC cell lines with UA resulted in the induction of Apoptosis. Treatment of HT29, SW480, and SW620 with UA resulted in increased expression of the pro-apoptotic proteins, p53 and p21. Similarly, UA treatment inhibited the anti-apoptotic protein expression of Bcl-2. Moreover, exposure of UA induced cytochrome c release and Caspase activation. Furthermore, UA was found to generate Reactive Oxygen Species (ROS) production in CRC cells. These findings indicate that UA possesses Anticancer potential and may be used therapeutically for the treatment of CRC.

Keywords

Apoptosis; Cell cycle arrest; Colorectal cancer; Reactive oxygen species; Urolithin A.

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