Apoptosis Induction in Primary Human Colorectal Cancer Cell Lines and Retarded Tumor Growth in SCID Mice by Sulforaphane

Ming-Jenn Chen,Ya-Ting Tsai,Chen-Wei Lin,Wei-Yu Tang,Che-Wei Hsu,Yi-Chiang Hsu,June-Fu Wu,Ya-Min Cheng

doi:10.1155/2012/415231

Abstract

We have investigated the anticancer effects of the dietary isothiocyanate sulforaphane (SFN) on colorectal cancer (CRC), using primary cancer cells lines isolated from five Taiwanese colorectal cancer patients as the model for colorectal cancer. SFN-treated cells accumulated in metaphase (SFN 6.25 μM) and subG1 (SFN 12.5 and 25 μM) as determined by flow cytometry. In addition, treated cells showed nuclear apoptotic morphology that coincided with an activation of caspase-3, and loss of mitochondrial membrane potential (ΔΨm). Incubations at higher SFN doses (12.5 and 25 μM) resulted in cleavage of procaspase-3 and elevated caspase-2, -3, -8, and -9 activity, suggesting that the induction of apoptosis and the sulforaphane-induced mitosis delay at the lower dose are independently regulated. Daily SFN s.c. injections (400 micromol/kg/d for 3 weeks) in severe combined immunodeficient mice with primary human CRC (CP1 to CP5) s.c. tumors resulted in a decrease of mean tumor weight by 70% compared with vehicle-treated controls. Our findings suggest that, in addition to the known effects on cancer prevention, sulforaphane may have antitumor activity in established colorectal cancer.

Highlights

Isothiocyanates (ITCs) are natural components of certain plants and vegetables that have selective biological activities and functions against carcinogenesis [1, 2], and many chemopreventive properties have been reported [3, 4]
We hypothesized that SFN could mediate the survival of primary colorectal cancer cell lines and inhibit their proliferation
A microscopic examination showed that following the exposure to SFN (25 μM) for 6 to 24 hours, the primary colon cancer cells have displayed a remarkable change in their morphology and SFN induced the death of cancer cells, which formed a suspension in the medium

Summary

Introduction

Isothiocyanates (ITCs) are natural components of certain plants and vegetables that have selective biological activities and functions against carcinogenesis [1, 2], and many chemopreventive properties have been reported [3, 4]. Sulforaphane (SFN), a potent cancer preventive agent, is a dietary isothiocyanate compound found as a precursor glucosinolate in cruciferous vegetables such as Brussels sprouts, cauliflower, and broccoli [7]. Interest in this agent has grown in recent years based on its putative beneficial pharmacological effects, which include antioxidant [8], antiinflammatory [9], and antitumor properties [10, 11]. Many studies indicate a positive correlation between the consumption of cruciferous vegetables and the decreased incidence of some tumors including prostate [16], cervical

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Conclusion