Thymoquinone has a broad range of pharmacological actions involving anti-oxidative, anti-inflammatory, immunomodulatory, anti-cancer, anti-microbial, hepatoprotective, hypoglycemic and antidiabetic, gastroprotective, neuroprotective, cardioprotective, nephroprotective, hypolipidemic, and anti-histaminic effects. It also showed a protective effect on reproductive system, respiratory system, and bone related disorders
[1]. TQ is generally safe to use but toxicity has been observed at higher doses (LD
50, 2.5 g/kg). In a study conducted by Abukhader, Wistar Albino rats administered with 30 mg/kg and 40 mg/kg of TQ showed signs of toxicity such as lethargy, abdominal swelling, piloerection, irritability, and weight loss. It was found that 22.5 mg/kg and 15 mg/kg are the maximum tolerated doses (MTD) through the intraperitoneal route (I.P) in male rats and female rats, respectively. When administered orally at doses of 500 mg/kg and 300 mg/kg, toxicity signs like dyspnea, abdominal distension, weight loss, diarrhea, and hypoactivity were observed. The MTD through oral route (P.O) for both male as well as female rats were reported as 250 mg/kg. MTD is the highest safe dose that can be administered without showing signs of toxicity
[2].
1.1. Role of Thymoquinone in Cancer
There are many preclinical studies (both in vivo and in vitro) which demonstrate the effect of TQ, given alone or in combination with other chemotherapeutic agents. It is known to target various processes of the cancer model such as cell cycle progression, proliferation, apoptosis, angiogenesis, migration, invasion, and metastasis of tumors. It also prevents oxidative damage and inhibits inflammatory responses
[1]. TQ showed therapeutic efficacy against a wide range of cancer including ovarian cancer
[6][7], breast cancer
[8][9], pancreatic cancer
[10], lung cancer
[11][12], fibrosarcoma
[13], neuroblastoma
[14], osteosarcoma
[15], myeloma
[16], oral cancer
[17], colon cancer
[18][19], prostate cancer
[20], squamous cell carcinoma
[21], gastric cancer
[22], leukemia
[23], cervical cancer
[24], liver cancer
[25][26], and skin cancer
[27]. In addition to its chemotherapeutic effects, it also diminishes the toxic side effects caused by chemotherapeutic agents.