Methylsulfonylmethane Demonstrates Anti-Cancer Effects in Colorectal Adenocarcinoma Cells

by | Mar 23, 2021 | 2020, Cancer, Colorectal (Colon), MSM (MethylsulfonylMethane)

Written by Angeline A. De Leon, Staff Writer. This study demonstrated the anti-cancer properties of methylsulfonylmethane (MSM) treatment on cell viability, cell cycle, and the metastatic potential of HT-29 cells.

cancerOver recent years, the prevalence of colorectal cancer has increased at an alarming rate 1. Treatment options for colorectal cancer (surgery, chemotherapy, radiation therapy) are generally limited in their ability to target molecular abnormalities at different stages of malignancy, which makes small molecule-based chemotherapy (therapeutic approach involving more specific molecular ) an attractive option for colorectal cancer treatment 2. MSM, a chemical found in green plants and animals 3, is classified by the U.S. Food and Drug Administration as a Generally Recognized as Safe (GRAS)-grade molecule with potent analgesic, anti-inflammatory properties 4,5. A number of epidemiological studies have attested to MSM’s anti-cancer effects, reporting its ability to inhibit invasive and migratory activity of prostate cancer cells 6, induce cell cycle arrest in gingival and lung cancer cells 7,8, and exert anti-proliferative effects in breast cancer cells via signaling transduction pathways 9. While promising, the anti-cancer properties of MSM remain to be explored in the context of colorectal cancer. Therefore, in a 2020 study 10 published in Anticancer Research, Kim and colleagues examined the effects of MSM treatment on cell viability, cell cycle arrest, and the metastatic potential of colorectal adenocarcinoma cells (HT-29 cells).

Experiments were carried out using a human colorectal adenocarcinoma cell line. Cells were cultured and treated with various concentrations of MSM (ranging from 0 to 350 mM) for 24h or 48h, and cell viability was assessed using an assay designed to measure cellular metabolic activity (MTT assay). Cell cycle was analyzed using flow cytometry and PI (propidium iodide) staining, and a tumor sphere formation assay was performed to identify cancer stem cells and their stemness potential (ability to replicate and differentiate into tumor cells). In addition, reverse transcription polymerase chain reaction (RT-PCR) analysis was carried out to examine the effects of MSM on relative mRNA expressions of stemness marker genes (sex determining region Y-box 2, SOX2; octamer-binding transcription factor 4, OCT4; nanog homeobox protein, NANOG).

Results from the MTT assay indicated that compared to the control solution, MSM suppressed the viability of HT-29 cells (based on percent relative absorbance of formazan solution) in a dose-dependent fashion after 24h (p < 0.01 for 50 mM, p < 0.001 for rest) and 48h (p < 0.001 for all). Flow cytometry showed that relative to control solution, treatment with MSM (at 200 mM) induced cell cycle arrest, based on the observed increase in the ratio of HT-29 cells in the G0/G1 phase (non-dividing phase of cell cycle) after 24h (p < 0.01). This was confirmed by PI staining, which suggested that treatment with 200 mM MSM increased the population of early apoptotic (p < 0.01) and late apoptotic cells (p < 0.001), compared to control. Finally, after 7 days of treatment, cells in the MSM group exhibited a significant decrease in the number of sphere formations, relative to control (p < 0.05 for 100 mM, p < 0.001 for 200 mM), along with a concentration-dependent decrease in apparent mRNA expressions of SOX2, OCT4, and NANOG, based on RT-PCR.

Altogether, findings indicate that supplementation with MSM is associated with a range of anti-cancer effects in colorectal adenocarcinoma cells. Not only did MSM reduce viability of HT-29 cells in a dose-dependent manner, treatment at doses of 200 mM triggered cell cycle arrest at the G0/G1 phase and effectively induced apoptosis of HT-29 cells, based on PI staining. By reducing the size and number of sphere formations and lowering the expression of stemness marker genes, MSM also successfully inhibited cancer cells’ potential for self-renewal and differentiation. In line with previous research, this in vitro study confirms MSM’s status as a dietary phytochemical with clinical applications in cancer prevention 2 and offers new evidence for its therapeutic promise in colon cancer cells specifically.

Source: Kim DH, Kang DY, SP N, et al. Methylsulfonylmethane induces cell cycle arrest and apoptosis, and suppresses the stemness potential of HT-29 cells. Anticancer Research. 2020; 40: 5191-5200. DOI: 10.21873/anticanres.14522.

Copyright © 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

Posted March 23, 2021.

Angeline A. De Leon, MA, graduated from the University of Illinois at Urbana-Champaign in 2010, completing a bachelor’s degree in psychology, with a concentration in neuroscience. She received her master’s degree from The Ohio State University in 2013, where she studied clinical neuroscience within an integrative health program. Her specialized area of research involves the complementary use of neuroimaging and neuropsychology-based methodologies to examine how lifestyle factors, such as physical activity and meditation, can influence brain plasticity and enhance overall connectivity.

References:

  1. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nature reviews Gastroenterology & hepatology. 2019;16(12):713-732.
  2. Surh YJ. Cancer chemoprevention with dietary phytochemicals. Nature reviews Cancer. 2003;3(10):768-780.
  3. Bertken R. “Crystalline DMSO”: DMSO2. Arthritis and rheumatism. 1983;26(5):693-694.
  4. Borzelleca J, Sipes I, Wallace K. Dossier in support of the generally recognized as safe (gras) status of optimsm (methylsulfonylmethane; msm) as a food ingredient. Food and Drug Administration: Vero Beach, FL, USA. 2007.
  5. Brayton CF. Dimethyl sulfoxide (DMSO): a review. The Cornell veterinarian. 1986;76(1):61-90.
  6. Kowalska K, Habrowska-Górczyńska DE, Domińska K, Urbanek KA, Piastowska-Ciesielska AW. Methylsulfonylmethane (organic sulfur) induces apoptosis and decreases invasiveness of prostate cancer cells. Environ Toxicol Pharmacol. 2018;64:101-111.
  7. Kim DH, Sp N, Kang DY, et al. Effect of Methylsulfonylmethane on Proliferation and Apoptosis of A549 Lung Cancer Cells Through G(2)/M Cell-cycle Arrest and Intrinsic Cell Death Pathway. Anticancer Res. 2020;40(4):1905-1913.
  8. Nipin NS, Kang DY, Kim BJ, et al. Methylsulfonylmethane Induces G(1) Arrest and Mitochondrial Apoptosis in YD-38 Gingival Cancer Cells. Anticancer Res. 2017;37(4):1637-1646.
  9. Joung YH, Lim EJ, Darvin P, et al. MSM enhances GH signaling via the Jak2/STAT5b pathway in osteoblast-like cells and osteoblast differentiation through the activation of STAT5b in MSCs. PLoS One. 2012;7(10):e47477.
  10. Kim DH, Kang DY, Sp N, et al. Methylsulfonylmethane Induces Cell Cycle Arrest and Apoptosis, and Suppresses the Stemness Potential of HT-29 Cells. Anticancer Res. 2020;40(9):5191-5200.