Abstract
Azima tetracantha is a traditionally used medicinal plant in the Ayurvedic system and folk medicines. The plant has been used for various purposes including inflammatory ailments, arthritis, and various types of toxicities. There are no available reports on its anticancer activity; hence, the study aimed to evaluate its anti-proliferative potential in gastric cancer cells (AGS and KATO III). We observed a dose-dependent decrease in cell proliferation in both the gastric cancer cells; furthermore, a concomitant reduction in the cellular antioxidant status was observed. Pre-treatment with A. tetracantha methanol extract showed a significant reduction in intracellular glutathione levels, and subsequently raised thiobarbituric acid reactive substances. Together with this, a significant increase in the cytochrome c release was noted in A. tetracantha treated cells, alongwith an increase in the expression of pro-apoptotic genes such as BAX, CASP3, CASP7 and APAF1. Furthermore, RTqPCR analysis indicated an increased expression of the anti-apoptotic gene BCL2 in a dose-dependent manner. In addition, to confirm the role of reactive oxygen species in the proliferation inhibition, DCFH-DA-based analysis was carried out, where a dose-dependent increase in ROS levels was observed in these cells. Overall, the study confirms the anticancer efficacy of A. tetracantha leaf methanol extract mediated through the induction of redox imbalance and cytochrome c release.
Highlights
The Western Ghats are an important source of such medicinal plants and the present study evaluated the possible application of a widely used anti-inflammatory medicinal plant Azima tetracantha for its possible application in gastric cancer control
Our results show a significant increase in the CASP3, CASP7, APAF1 and BAX genes in A. tetracantha (p < 0.05) methanol-extract-treated AGS and Kato-III
Our data show that the A. tetracanthaextract-mediated increase in BAX expression levels in both Kato-III and AGS cancer cells was higher than the increase obtained for BCL2 mRNA levels, leading to an increase in the BAX/BCL2 mRNA ratio, which has already been used to explain the anticancer effects of flavanols on breast and prostate cancer cells [28]
Summary
Genetic factors are an important regulator of the carcinogenic responses in the stomach; among these, the most prominent is the mutations of a tumor suppressor gene, CDH1, that encodes the E-cadherin-class proteins [1]. Apart from these factors, infections of Helicobacter pylori and certain human papillomaviruses are reported to have a significant association with gastric carcinoma [2,3]. Increased consumption of fatty foods [5], and diets rich in sugars [6] and salts [7] are reported to increase the incidence of gastric cancer
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