Antineoplastic and apoptotic potential of traditional medicines thymoquinone and diosgenin in squamous cell carcinoma.
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-G(1) 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.
School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, West Bengal, India.
Subhasis
S
Das
Kaushik Kumar
KK
Dey
Goutam
G
Dey
Ipsita
I
Pal
Abhijit
A
Majumder
Sujata
S
MaitiChoudhury
Subhas C
SC
kundu
Mahitosh
M
Mandal
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D016227:Benzoquinones / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004144:Diosgenin / Q000494:pharmacology*; D004587:Electrophoresis, Agar Gel; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008519:Medicine, Traditional; D051379:Mice; D008856:Microscopy, Fluorescence; D010766:Phosphorylation
D000970:Antineoplastic Agents; D016227:Benzoquinones; D004144:Diosgenin; C003466:thymoquinone