Combination cisplatin and sulforaphane treatment reduces proliferation, invasion, and tumor formation in epidermal squamous cell carcinoma

Abstract

Epidermal squamous cell carcinoma is an extremely common type of cancer. Early tumors can be successfully treated by surgery, but recurrent disease is aggressive and resistant to therapy. Cisplatin is often used as a treatment, but the outcome is rarely satisfactory. For this reason new strategies are required. Sulforaphane is a diet‐derived cancer prevention agent that is effective in suppressing tumor growth in animal models of skin cancer. We monitored the efficacy of sulforaphane and cisplatin as a combined therapy for squamous cell carcinoma. Both agents suppress cell proliferation, growth of cancer stem cell spheroids, matrigel invasion and migration of SCC‐13 and HaCaT cells, and combination treatment is more efficient. In addition, SCC‐13 cell derived cancer stem cells are more responsive to these agents than non‐stem cancer cells. Both agents suppress tumor formation, but enhanced suppression is observed with combined treatment. Moreover, both agents reduce the number of tumor‐resident cancer stem cells. SFN treatment of cultured cells or tumors increases apoptosis and p21Cip1 level, and both agents increase tumor apoptosis. We suggest that combined therapy with sulforaphane and cisplatin is efficient in suppressing tumor formation and may be a treatment option for advanced epidermal squamous cell carcinoma.

Sulforaphane Suppresses the Growth of Triple-negative Breast Cancer Stem-like Cells In vitro and In vivo

“…Sulforaphane has previously been shown to inhibit the proliferation of skin and breast cancer cells (12,13). We assessed the antiproliferative effects of sulforaphane using a mitochondrial activity test (MTT assay) in two TNBC cell lines: the mouse mammary carcinoma cell line, JygMC(A) GFP/Luc, and the human breast cancer cell line, MDA-MB-231-Luc-D3H1 (16,20).…”

“…These sulfur-rich compounds are hydrolyzed by the plant endogenous enzyme, myrosinase, to release an active compound, sulforaphane (11). Recently, sulforaphane has been shown to target the self-renewal properties of CSCs in a variety of cancer types including skin, breast, pancreatic, and glioblastoma (12)(13)(14)(15). Despite the increasing evidence and interest shown in modulating effects of sulforaphane on CSCs and their involvement with the early development of tumor formation, limited data is available for the utility of sulforaphane to prevent the CSC-mediated processes of tumor development and maintenance.…”

Combination of Broccoli Sprout Extract and Zinc Provides Better Protection against Intermittent Hypoxia-Induced Cardiomyopathy Than Monotherapy in Mice

“…6 Oxidative Medicine and Cellular Longevity growth in a triple-negative breast cancer line by inducing autophagic cell death and premature senescence [48]. Epidermal squamous cell carcinoma and malignant mesothelioma can be treated using a combination of SFN and cisplatin, inhibiting tumor cell proliferation and accelerating tumor cell autophagy [49,50]. Furthermore, the combination of SFN and myricetin can induce fat cell apoptosis via Akt-mediated mitochondrial apoptosis [51], suggesting a novel strategy for the treatment of obesity.…”

Antitumor activity of sulforaphane in mice model of skin cancer via blocking sulfatase‐2

“…The effect of sulforaphane differs in normal cells as compared to cancer cells. In cancer cells, sulforaphane‐effect is accompanied by the induction of cellular apoptosis as well as inhibition of cell proliferation through enhancing the silencing of tumor promoter genes associated with reactivation of tumor suppressor genes …”