Diallyl sulfide induces apoptosis in Colo 320 DM human colon cancer cells: involvement of caspase-3, NF-kappaB, and ERK-2.
Chemoprevention is regarded as one of the most promising and realistic approaches in the prevention of human cancer. Diallyl sulfide (DAS), an organosulfur component of garlic has been known for its chemopreventive activities against various cancers and also in recent years, numerous investigations have shown that sulfur-containing compounds induce apoptosis in multiple cell lines and experimental animals. Thus the present study was focused to elucidate the anticancerous effect and the mode of action of DAS against Colo 320 DM colon cancer cells. DAS induced apoptosis in Colo 320 DM cells was revealed by flow cytometer analysis and phosphatidyl serine exposure. DAS also promoted cell cycle arrest substantially at G2/M phase in Colo 320 DM cells. The production of reactive oxygen intermediates, which were examined by 2,7-dichlorodihydrofluorescein diacetate (H2DCF-DA), increased with time, after treatment with DAS. The activities of alkaline phosphatase (ALP) and lactate dehydrogenase (LDH) were decreased upon DAS treatment, which shows the antiproliferative and the cytotoxic effects, respectively. The expression of NF-kappaB was upregulated in DAS treated cells, compared to normal cells. Further, DAS promoted the expression of caspase-3 and suppression of Extracellular Regulatory Kinase-2 (ERK-2) activity in Colo 320 DM cells that was determined by Western blot analysis. In conclusion, DAS increased the production of ROS, caused cell cycle arrest, decreased cell proliferation and induced apoptosis in Colo 320 DM cells. Thus, this study put forward DAS as a drug that can possibly be used to treat cancers.
Sriram
Narayanan
N
Department of Biochemistry, University of Madras, Guindy Campus, Chennai, Tamil Nadu 600 025, India.
Kalayarasan
Srinivasan
S
Ashokkumar
Pandurangan
P
Sureshkumar
Ananthasadagopan
A
Sudhandiran
Ganapasam
G
D000498:Allyl Compounds / Q000737:chemistry / Q000494:pharmacology*; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms; D053938:DNA Fragmentation; D005737:Garlic / Q000737:chemistry; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010938:Plant Oils / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013440:Sulfides / Q000737:chemistry / Q000494:pharmacology*
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D000972:Antineoplastic Agents, Phytogenic; D016328:NF-kappa B; D010938:Plant Oils; D017382:Reactive Oxygen Species; D013440:Sulfides; C038491:allyl sulfide; D019950:Mitogen-Activated Protein Kinase 1; D053148:Caspase 3