Introduction
Colon cancer is the third most common cancer in men and women having a high mortality rate worldwide. Cancer recurrence is common in 50% of patients with colon cancer indicating that the modern strategies of cancer therapy are unsuccessful.
Researchers are investigating plant‐ derived phytochemicals and evaluating their effects alone and with traditional chemotherapeutics. Considering that these compounds have minimal toxicity and are commercially available, phytochemicals (polyphenols, flavonoids, phenolic agents etc) have garnered considerable attention as potential anti-cancer agents.
Zingerone (ZO) is one of the major active phenolic agents of ginger (Zingiber officinale). ZO has many pharmcological properties like antioxidant, antiangiogenic, and antitumor. This study investigated the oxidative stress‐ mediated apoptosis through alteration of mitochondrial membrane potential (MMP) by the action of ZO in colon cancer cells (HCT116).
Fig 1 (Upper image)- Ginger (Zingiber officinale) rhizome; (Lower image)- Chemical structure of Zingerone
Research
Ginger derivatives of ZO treatment significantly reduced HCT116 cell proliferation and effectively suppressed cell growth in different types of cancer models while producing no toxic effect on normal cells. Oxidative stress plays a vital role in oxidative damage arbitrated apoptosis in colon cancer. An imbalance between the overgeneration and/or elimination of ROS causes severe oxidative damage to intracellular molecules. Herein, an increased ROS generation was noticed, indicating high fluorescence intensity (Figure B) in ZO‐treated cells.
Fig B- Intracellular ROS generation of ZO on HCT116 cells measured DCFH‐DA staining.
The mitochondria are a major cellular organelle, essential for apoptosis. Mitochondrial outer membrane permeabilization is a key event of the apoptotic cell death. The release of cytochrome c from the mitochondria into the cytosol provides apoptotic stimuli. Here, ZO effectively induced oxidative stress to mediate alteration of outer MMP, indicating diminished fluorescence intensity in a concentration‐dependent manner. (Figure 2)
Fig 2- The effect of ZO on MMP was evaluated with HCT116 cells using the Rhodamine 123. (Upper image) -Control and different concentrations of cells treated with ZO (2.5, 5, and 10 µM) show that fluorescence intensity was decreased as red arrow indicates collapsed mitochondria matrix. (lower image)-The depicted fluorescence intensity was detected by a spectrofluorometer
Many chemotherapeutic drugs target intracellular component of DNA to induce apoptosis which is associated with chromatin condensation, nuclear disintegration, and membrane blebbing. Excess production of ROS could lead to induced apoptotic morphological changes in cancer cells.
Plant‐derived phytochemical induce oxidative stress‐mediated cancer cell death through oxidative DNA damage. The ROS provoked oxidative stress‐mediated apoptosis- confirmed by comet assay, indicating an increased percentage of DNA damage in ZO‐treated cells. ZO induced apoptotic features (chromatin condensation, nuclear disintegration, membrane blebbing, and apoptotic cell death) as confirmed by AO/EtBr (Acridine Orange/Ethidium Bromide) (Figure 3) and Hoechst staining (Figure 4).
Fig 3- Fluorescence microscopy images of apoptotic morphology changes by AO/EtBr staining; (Upper image)- control and different concentrations (2.5, 5, and 10 µM) of ZO‐treated cells shows increased percentage of apoptotic cells in a concentration‐dependent manner (red arrow indicates apoptosis cells). (Lower image)- Bar diagram shows % apoptotic cells were calculated.
Fig 4- Hoechst staining; control and different concentrations (2.5, 5, and 10 µM) of ZO‐treated cells shows increased fragmented nuclei and membrane blebbing indicate red arrow marks.
Conclusion
The investigation concluded that ZO can show antitumor effects in HCT116 cells through stimulating oxidative stress in HCT116 cells suggesting that ZO is a hopeful anticancer agent, which can be further followed up for the prevention and/or treatment of colon cancer.
Reference
Su P, Veeraraghavan VP, Krishna Mohan S, Lu W.
A ginger derivative, zingerone—a phenolic compound—induces ROS‐mediated apoptosis in colon cancer cells (HCT‐116).
Journal of Biochemistry and Molecular Toxicology, 2019;
e22403.
DOI
By Debangana Banerjee
Comments