Anticancer effect of Limonin against benzo(a)pyrene‐induced lung carcinogenesis in Swiss albino mice and the inhibition of A549 cell proliferation through apoptotic pathway

Abstract

The main purpose of the current study is to reveal the anticancer action of limonin against benzo(a)pyrene [B(a)P]‐treated lung carcinogenesis in Swiss albino mice and A549 lung cancer cells. B(a)P was orally supplemented (50 mg/kg body weight) twice a week for four weeks induction of lung cancer in mice. The lung weight, body weight, incidence of tumor, lipid peroxidation, carcinoembryonic antigen (CEA), enzymatic and nonenzymatic antioxidants (superoxide dismutase, GPx, glutathione, glutathione reductase, catalase, and glutathione S‐transferase), serum marker enzymes (aryl hydroxylase, lactate dehydrogenase, 5′‐nucleotidases, and γ‐glutamyl transpeptidase), and inflammatory mediators (interleukin‐1β, interleukin‐6, and tumor necrosis factor‐α) were estimated. Moreover, a histopathological study of lung tissues was supported by the biochemical analysis. Furthermore, the anticancer activity of limonin on A549 cells was measured by cell viability, production of reactive oxygen species (ROS), apoptotic morphological changes by AO/EtBr staining. Additionally, the status of apoptosis protein (caspase‐9 and ‐3) expressions was analyzed by the colorimetric analysis. B(a)P‐induced mice showed increased lipid peroxidation, CEA, serum marker enzymes and inflammatory cytokines levels with simultaneously decreased in the nonenzymatic and enzymatic antioxidants levels. Limonin supplements significantly reverted back to all these changes in this manner, showing the efficiency of anticancer effect. Furthermore, our in vitro study also supported the anticancer effect of the treatment of limonin‐enhanced apoptosis by loss of cell viability, improved ROS production, apoptotic morphological changes, and apoptosis protein expression were analyzed. Overall, these results suggest the anticancer potential of limonin against B(a)P‐induced lung cancer in Swiss albino mice and A549 lung cancer cells.

Limonin induces apoptosis of HL‐60 cells by inhibiting NQO1 activity

“…It has a variety of biological activities, such as anticancer, antioxidant, anti-inflammatory, neuroprotective, and antibacterial. In recent years, a large number of studies have shown that limonin has great potential in cancer prevention and treatment by scavenging free radicals, stimulating the activity of glutathione transferase, inhibiting the activity of carcinogenic chemicals, and inhibiting the proliferation of tumor cells (Bodduluru et al, 2014;Galal et al, 2015, Gong et al, 2019. These results were similar to the researches of Akihisa et al (2013), Yao et al (2018), andChidambara Murthy et al (2011), which further proved that limonin inhibited the growth of HL-60 cells by inducing apoptosis through mitochondrial-dependent pathway.…”

“…It has a variety of biological activities, such as anticancer, antioxidant, anti‐inflammatory, neuroprotective, and antibacterial. In recent years, a large number of studies have shown that limonin has great potential in cancer prevention and treatment by scavenging free radicals, stimulating the activity of glutathione transferase, inhibiting the activity of carcinogenic chemicals, and inhibiting the proliferation of tumor cells (Bodduluru et al., 2014; Galal et al., 2015, Gong et al, 2019). For example, Bae et al.…”

“…(2020) found that limonin can induce cell apoptosis by activating p53 signal pathway, reducing the viability of SKOV‐3, A2780, and RMUG‐S ovarian cancer cells, and reversing the drug resistance of CISRSKOV‐3 cells by activating apoptosis. Gong et al (2019) found that limonin can effectively inhibit lung cancer induced by benzopyrene (BP) in mice, and in vitro experiments showed that limonin can promote the production of reactive oxygen species (ROS) and induce apoptosis of A549 lung cancer cells. In addition, Berhow et al.…”

<p>Diallyl Sulfide-Mediated Modulation of the Fatty Acid Synthase (FASN) Leads to Cancer Cell Death in BaP-Induced Lung Carcinogenesis in Swiss Mice</p>

“…34 The significant drop in the relative lung weight and increased body weight by DAS were consistent with previous chemopreventive studies of various plant extracts and their active components in chemically induced lung cancer. [35][36][37] The histopathological data studies confirmed the tumor growth inhibitory and the protective effect of DAS in the lungs ( Figure 5A). The data also revealed that the pretreatment of DAS controlled the invasion of cancer cells in the liver leading to apoptosis ( Figure 5B).…”

Analysis of the Components in Moxa Smoke by GC‐MS and Preliminary Discussion on Its Toxicity and Side Effects

“…In fact, it has been reported that moxa smoke can cause related symptoms, such as eustachian tube and throat itching, eye pain, tonsil enlargement, and other symptoms [ 30 – 33 ]. Tar contains two-tenths of a million of a kind of thick cyclic aromatic hydrocarbon called benzo(a)pyrene, which is a strong carcinogen [ 34 ]. In a few cases, patients undergoing moxibustion treatment or after treatment had erythema, blisters, and other hypersensitive symptoms, and these conditions disappeared after leaving the moxa smoke environment [ 35 – 37 ].…”