Abstract
Thymoquinone (TQ) and diosgenin (DG), the active ingredients obtained from black cumin (Nigella sativa) and fenugreek (Trigonella foenum graecum), respectively, exert potent bioactivity, including anticancer effects. This study investigated the antineoplastic activity of these agents against squamous cell carcinoma in vitro and sarcoma 180–induced tumors in vivo. TQ and DG inhibited cell proliferation and induced cytotoxicity in A431 and Hep2 cells. These agents induced apoptosis by increasing the sub-G1 population, LIVE/DEAD cytotoxicity, chromatin condensation, DNA laddering and TUNEL-positive cells significantly (P<0.05). Increased Bax/Bcl-2 ratio, activation of caspases and cleavage of poly ADP ribose polymerase were observed in treated cells. These drugs inhibited Akt and JNK phosphorylations, thus inhibiting cell proliferation while inducing apoptosis. In combination, TQ and DG had synergistic effects, resulting in cell viability as low as 10%. In a mouse xenograft model, a combination of TQ and DG significantly (P<0.05) reduced tumor volume, mass and increased apoptosis. TQ and DG, alone and in combination, inhibit cell proliferation and induce apoptosis in squamous cell carcinoma. The combination of TQ and DG is a potential antineoplastic therapy in this common skin cancer.
Highlights
Skin cancer is the most common form of human cancer
In this study we investigate the antitumor activity of thymoquinone (TQ) and/or diosgenin (DG) in A431, Hep2 and RPMI 2650 squamous cell carcinoma (SCC) cells in vitro and sarcoma 180–induced solid tumors in vivo
Cell culture Human SCC A431, Hep2 and RPMI 2650 cells were obtained from National Center for Cell Science (Pune, India) and HaCat were obtained from American Type Culture Collection (ATCC) 10801 University Boulevard Manassas, VA 20110, USA
Summary
Skin cancer is the most common form of human cancer. It is estimated that over one million new cases occur annually. The annual rates of all forms of skin cancer are increasing each year worldwide. The two most common forms of skin cancer are basal cell carcinoma and squamous cell carcinoma (SCC). Together, these two are referred to as nonmelanoma skin cancer. SCC is the second most common form of nonmelanoma skin cancer and accounts for 20% of cutaneous malignancies [1,2]
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