Mitochondrial Dysfunction and Induction of Apoptosis in Hepatocellular Carcinoma and Cholangiocarcinoma Cell Lines by Thymoquinone

Abstract

Thymoquinone (TQ), a plant-based bioactive constituent derived from the volatile oil of Nigella sativa, has been shown to possess some anti-neoplastic activities. The present study aimed to investigate the mitochondria and apoptosis observed when TQ is applied against hepatocellular carcinoma (HepG2) and cholangiocarcinoma (HuCCT1) cells, two of the most common primary tumors of the liver. All cell lines were treated with increasing concentrations of TQ for varying durations. The anti-proliferative effect of TQ was measured using the methoxyphenyl-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay and resulted in dose- and time-dependent growth inhibition in both cell lines. Cell cycle, apoptosis, and assessment of mitochondria viability by morphology assessment and evaluation of the mitochondrial membrane potential were investigated. The present study confirms that TQ caused cell cycle arrest at different phases and induced apoptosis in both cell lines. A systematic review of rodent animal models was also carried out. Overall, our data seem to represent the most robust results, suggesting that TQ possesses promising therapeutic potential as an anti-tumor agent for the treatment of hepatocellular carcinoma and cholangiocarcinoma.

The Cytotoxic Effect of Thymoquinone Enhance on HepG2 Cell Line due to Induction of Fenton Reaction by Hydrogen Peroxide: An In Vitro and In Silico Study

“…In the current study, IC 50 of hydrogen peroxide was determined approximately 310 µM, which confirms the findings of Tan et al (2020). In addition, The IC 50 of TQ was reported around 192 µM, which confirms the report of Celebioğlu et al (2022) and contradicts the findings of Abdualmjid andSergi, (2022) andZhang et al (2021). This discrepancy may be associated to the role of cell culture condition, such as the type of culture medium and the number of cell passage.…”

Characterization of Thymoquinone-Sulfobutylether-β-Cyclodextrin Inclusion Complex for Anticancer Applications

“…One possible explanation is that TQ induces apoptosis in HepG2 cells [ 47 ]. In addition, TQ exhibits other anti-cancer properties, such as inhibiting cell proliferation, migration, and invasion [ 48 ], as well as inducing cell cycle arrest [ 49 ] and suppressing tumor angiogenesis [ 50 ]. The sensitivity of HepG2 liver cancer cells to TQ may be influenced by several mechanisms.…”

Potential anticancer properties and mechanisms of thymoquinone in colorectal cancer

“…Nigella sativa L. (also known as black cumin, black seed, and black caraway) is a spice that also has been used in traditional medicine against a variety of acute/chronic diseases such as asthma, bronchitis, rheumatism, headache, back pain, anorexia, amenorrhea, paralysis, inflammation, mental disability, eczema, obesity, infections, depression, dysentery, hypertension, gastrointestinal, cardiovascular, hepatic, and renal disorders based on antimicrobial/viral, antioxidative, anti-diabetic, anti-inflammatory, and immunomodulatory properties of its components specifically TQ [ 17 – 24 ].…”

“…Thanks to chemo preventive and anti-tumor properties, TQ and N. sativa has been used against various neoplasms including lung, hepatobiliary, liver, breast, pancreas, hematopoietic/leukemia, kidney, bladder, cervix, skin, ovary, prostate, osteosarcoma, fibrosarcoma, and colorectal cancers in-vivo and in-vitro with less cytotoxicity against normal cells [ 18 , 20 , 22 , 25 , 30 ]. Different studies showed that TQ could target various mechanisms involved in cancer progression including proliferation [ 21 , 22 , 24 , 30 – 38 ], migration [ 21 , 30 , 32 , 34 – 36 , 39 – 41 ] invasion/metastasis [ 22 , 30 , 32 , 35 , 41 , 42 ], angiogenesis [ 22 , 31 , 41 ], colony formation [ 35 , 36 ], tubulogenesis [ 43 , 44 ], epithelial-mesenchymal transition (EMT) [ 32 , 34 , 42 , 45 ], autophagy [ 45 – 47 ], and cancer stemness [ 43 ].…”