Lung cancer induced by Benzo(A)Pyrene: ChemoProtective effect of sinapic acid in swiss albino mice

Abstract

Cancer of lung is the utmost typical cause of death and the number of cases is increasing rapidly, which has emerged as a major leading health problem. A large amount of reports suggested that Benzo(a)pyrene [B(a)P] in cigarette smoke plays the major function in an initiation of cancer of lung. Cancer prevention or chemoprevention has become a compelling approach recently for treatment of lung cancer. So, discovering a fresh candidate with reduced toxicity for targeting lung cancer is vital and urgent. Sinapic acid which is a widely extracted in various vegetables and fruit exhibits rich anti-oxidant content, anti-inflammatory and anti-tumor activity. But, the chemopreventive action of sinapic acid against lung cancer initiated by B[a]P remain unclear. Following, an in-vivo B[a]P-stimulated lung cancer in swiss albino mice and an in-vitro human lung cancer cell (A549) model were established to examine the chemopreventive activities of sinapic acid. The levels of immunoglobulins (IgG and IgM), oxidative and inflammatory markers, and tumor markers level was studied using kits and standard methods. The results showed administration of sinapic acid ameliorates the exposure of B[a]P mediated lung cancer in swiss albino mice by a decline in IgG and IgM level, leukocyte count, neutrophil function tests, soluble immune complex, lipid peroxidation, pro-inflammatory cytokines, tumor markers (AHH, LDH, GGT, 5′NT and CEA) and enhanced phagocytic index, activity index and antioxidant defense enzymes. In addition, in-vitro studies showed potential cytotoxicity against human lung cancer and exhibited a potential cytotoxic (MTT assay) and apoptotic activity by elevation of ROS production and caspase activity (caspase-3 and caspase-9). Collectively, the results, clearly specifies sinapic acid can be utilized as an effective chemo preventative agent against lung carcinogenesis.

Mechanisms involved in the anticancer effects of sinapic acid

“…SA-treated cells showed increased ROS levels in the treated cells (108.32 ± 7.32) compared to untreated cells (76.41 ± 7.09) (Janakiraman et al 2014). Hu et al (2021) reported that in human lung A549 cells, SA (50 and 75 μM) increased ROS accumulation in the treated cells compared to the untreated cells. Similar results were reported by Badr et al (2019) in A549 and Caco-2 cancer cell lines.…”

“…Supplementation of SA was found to be effective in improving the abnormalities induced by DMBA. Another study also reported the ability of SA to improve cellular antioxidants against lung cancer (Hu et al 2021). Tungalag et al (2021) showed that the expression of antioxidant proteins such as SOD1, SOD2 and CAT were significantly increased upon SA treatment in SH-SY5Y human neuroblastoma cells.…”

“…Modulation of immunoglobulin production during cancer can be considered as an alternate approach for the prevention of the disease. The effect of SA on modulating immunoglobulin levels in lung cancer in rats has been reported (Hu et al 2021). SA administration markedly improved the levels of IgG and IgA in the treated animals compared to the untreated animals.…”

“…Cancer chemoprevention and therapy depends on the investigation of these marker enzymes. Hu et al (2021) have studied the effect of SA on changes in the levels of serum marker enzymes in benzo(a)pyrene (B(a)P) induced lung cancer in mice. The levels of serum CEA, AHH, LDH, GGT, and 5'NT were abnormally raised in the B(a)P-induced lung cancer-bearing mice.…”

“…The most common one being anemia because of acute or chronic blood loss, marrow involvement by the malignancy, marrow suppressive effects of chemotherapy or radiation therapy (Yoshida et al 2022). Hu et al studied the effect of SA on hematological alterations in experimental lung cancer (Hu et al 2021). Changes in the levels of hematological parameters such as leucocytes, neutrophils, lymphocytes, absolute lymphocyte count and absolute neutrophil count were observed in lung cancer-bearing animals.…”