Methylsulfonylmethane Induces Cell Cycle Arrest and Apoptosis, and Suppresses the Stemness Potential of HT-29 Cells

Abstract

Background/Aim: Colorectal cancer is one of the most common malignancies worldwide. Small moleculebased chemotherapy is an attractive approach for the chemoprevention and treatment of colorectal cancer. Methylsulfonylmethane (MSM) is a natural organosulfur compound with anticancer properties, as revealed by studies on in vitro models of gingival, prostate, lung, hepatic, and breast cancer. However, the molecular mechanisms underlying the effects of MSM in colon cancer cells remain unclear. Materials and Methods: Here, we investigated the effects of MSM, especially on the cell cycle arrest and apoptosis, in HT-29 cells. Results: MSM suppressed the viability of HT-29 cells by inducing apoptosis and cell cycle arrest at the G 0 /G 1 phase. MSM suppressed the sphereforming ability and expression of stemness markers in cells. Conclusion: MSM has anti-cancer effects on HT-29 cells, and induces cell cycle arrest and apoptosis, while suppressing the stemness potential.Colorectal cancer is one of the most commonly diagnosed malignancies worldwide, and its prevalence is increasing in the recent years (1). It is classified on the basis of histopathological features, including the clinical, morphological, and molecular characteristics of the cancer (2).Among the various histopathological types, adenocarcinoma accounts for 95% to 98% of all cases of colorectal cancer (3, 4). Colorectal cancer is usually treated by surgery, radiation therapy, or chemotherapy (5). Among these treatment strategies, chemotherapy can generally be administered either before or after surgery for reducing tumor size and the risk of recurrence ( 6). Chemotherapy may also be administered for providing relief from the symptoms of colorectal cancer in cases where the tumor cannot be removed surgically, or in cases of severe metastasis to other sites of the body (6). Therefore, it is necessary to develop novel chemotherapeutic agents for targeting molecular abnormalities at various stages of malignancies, which requires continuous efforts for the discovery of novel compounds and elucidation of the mechanisms underlying their mode of action.Methylsulfonylmethane (MSM) is a simple organosulfur compound, which is also known as dimethylsulfone, methylsulfone, sulfonyl bis methane, organic sulfur, or crystalline dimethyl sulfoxide (7). MSM occurs naturally in plants, animals, and various natural products (7). It has been recognized as a safe substance, and the US Food and Drug Administration (FDA) classified MSM as an 'Generally Recognized as Safe (GRAS)' grade molecule (8). It has been reported that MSM has numerous physiological functions, and is particularly well-known due to its analgesic properties in chronic pain caused by inflammatory diseases (9).In the recent past, numerous studies have reported the anticancer properties of MSM using in vitro models (10). For instance, it has been reported that MSM induces ER stressmediated apoptosis in HCT116 cells (11). Another study demonstrated the antiproliferative effects of MSM and suggested its inhibitory po...

Inhibition of colorectal cancer tumorigenesis by ursolic acid and doxorubicin is mediated by targeting the Akt signaling pathway and activating the Hippo signaling pathway

“…Flow cytometry was used to assess the apoptotic status of cells following treatment with different drugs. It has been reported that the sub-G 1 phase is characterized by apoptosis induction (69). The proportion of cells in sub-G 1 phase was significantly increased following treatment with the combination of 15 µM UA + 1.5 µM DOX compared with the control and either agent alone (Figs.…”

Iron Metabolism as a Potential Mechanism for Inducing TRAIL-Mediated Extrinsic Apoptosis Using Methylsulfonylmethane in Embryonic Cancer Stem Cells

“…MSM is a natural sulfur-containing compound with a well-known anticancer activity against various cancer cells in vitro and in vivo. Some studies have shown that it can inhibit the tumorsphere formed by colorectal cancer cells [ 30 ] and suppress stem cell marker protein expression in breast cancer tissue [ 36 ]. Considering the high dose of MSM, it has already been tested as nontoxic in normal cells and animal models, and up to a concentration of 6–8 g/kg/day through oral administration, mice remained healthy and vigorous [ 37 ].…”

“…This compound exerts various physiological activities, including antioxidant and anti-inflammatory activities [ 26 , 27 ]. MSM is well known for its anticancer activity against various cancer types, including breast [ 28 ], lung [ 29 ], colorectal [ 30 ], and gingival cancers [ 31 ]. This MSM can also synergize chemotherapeutic drug activity to increase efficacy and reduce the adverse effect caused by the chemotherapeutic drug [ 32 , 33 ].…”

Protective effects of methylsulfonylmethane (MSM) on barrier function injury of porcine intestinal epithelial cells (IPEC-J2) induced by lipopolysaccharide (LPS)

“…In addition, other relevant studies have found that MSM can also block G0/G1 cell cycle progression. Studies showed that 200 mmol/L MSM can reduce or inhibit cell viability by inducing apoptosis and cell cycle arrest in the G0/G1 phase, such as prostate cancer (PC) cells, HT-29 cells, and gingival cancer cells (Nipin et al 2017;Kowalska et al 2018;Kim et al 2020). It was found that the regulation of MSM on the cell cycle is closely related to cyclin and proapoptotic proteins, such as cyclin D, cyclin E, and Bax (Kowalska et al 2018).…”