Altered presence of extra cellular matrix components in murine skin cancer: Modulation by Azadirachta indica leaf extract

Abstract

Background and aim Although, the anticancer potential of Aqueous Azadirachta indica leaf extract (AAILE) has been robustly established against cutaneous squamous cell carcinoma (SCC) in mice, however, its ability in modulating tumor associated extra cellular matrix (ECM) is largely unknown. Therefore, the present study was conceived to explore changes in ECM during murine skin cancer and its chemoprevention by AAILE. Experimental procedure Skin tumors were induced using a two-stage model of carcinogenesis employing topical application of 7,12-Dimethylbenz(a)anthracene (DMBA) and 12-O-tetradecanoyl phorbol-13-acetate (TPA) as carcinogen and promoter respectively. AAILE was administered orally to the animals. Male Laca mice were divided into four groups: control, AAILE, DMBA/TPA and AAILE + DMBA/TPA. Results The tumors obtained in DMBA/TPA and AAILE + DMBA/TPA groups were histologically identified as SCC. Tumor induction in these groups was accompanied by raised serum carcinoembryonic antigen (CEA) levels when compared to control counterparts. Assessment of hydroxyproline levels and histochemical staining with sirius red and trichrome stain revealed an increase in collagen in tumors of DMBA/TPA group. An increase in glycosaminoglycans (GAGs) levels was also observed in DMBA/TPA group as made evident by biochemical studies and histochemical staining using mucicarmine and alcian blue-periodic acid schiff’s stain. Administration of AAILE to DMBA/TPA treated animals caused a decrease in collagen and GAG levels along with a decrease in serum CEA levels. Conclusion Skin tumors exhibited altered presence of ECM components which is indicative of a modified ECM. AAILE administration antagonised tumor associated ECM alterations which may be contributing to its chemopreventive activity as reported previously.

Glucosidase inhibitor, Nimbidiol ameliorates renal fibrosis and dysfunction in type-1 diabetes

“…Adverse ECM accumulation in glomerulus and tubulointerstitium promotes renal fibrosis and subsequent deterioration of renal function 2 . ECM regulation by neem-derived compounds has already been shown in cancer studies 33,34 . Therefore, in our current study, we examined the effect of Nimbidiol on the expression of important ECM proteins such as collagen IV (Col IV), fibronectin, and elastin in the diabetic kidney.…”

“…A wide range of neem extracts and neem-derived compounds have also been reported to show antihyperglycemic activity 29 . Moreover, earlier studies have also suggested that bioactive compounds from A. indica regulate ECM proteins by modulating expression of MMPs in different diseases including wide-spectrum cancer studies [30][31][32][33][34] . Recently, therapeutic intervention of neem extract has been shown to abrogate inflammation-driven renal fibrosis by reducing ECM accumulation in UUO nephropathy 35 .…”

A review on the pathogenesis of cutaneous non-melanoma skin cancer (NMSC) and selected herbs as chemoprotective agents

“…Chugh et al (2018) observed that AAILE treatment caused a marked reduction in skin papilloma formation as unveiled via scrutinizing the cell proliferation, cell count, DNA/amide ratio, ODC, ATM, and LDH within skin/papilloma of mice. After that, Chugh and Koul (2021) observed that AAILE treatment decreased the GAGs levels, collagen levels, and CEA levels, and thus modulated the ECM to reduce the metastasis of skin carcinoma in the DMBA/TPA-induced murine skin cancer model. Table 1 lists a few findings validating its protective role against NMSC.…”