Neem leaf extract inhibits mammary carcinogenesis by altering cell proliferation, apoptosis, and angiogenesis

Abstract

Plant-based medicines are useful in the treatment of cancer. Many breast cancer patients use complementary and alternative medicine in parallel with conventional treatments. Neem is historically well known in Asia and Africa as a versatile medicinal plant with a wide spectrum of biological activities. The experiments reported herein determined whether the administration of an ethanolic fraction of Neem leaf (EFNL) inhibits progression of chemical carcinogen-induced mammary tumorigenesis in rat models. Seven-week-old female Sprague Dawley rats were given a single intraperitoneal injection of N-methyl-N-nitrosourea (MNU). Upon the appearance of palpable mammary tumors, the rats were divided into vehicle-treated control groups and EFNL-treated groups. Treatment with EFNL inhibited MNU-induced mammary tumor progression. EFNL treatment was also highly effective in reducing mammary tumor burden and in suppressing mammary tumor progression even after the cessation of treatment. Further, we found that EFNL treatment effectively upregulated proapoptotic genes and proteins such as p53, B cell lymphoma-2 protein (Bcl-2)-associated X protein (Bax), Bcl-2-associated death promoter protein (Bad) caspases, phosphatase and tensin homolog gene (PTEN), and c-Jun N-terminal kinase (JNK). In contrast, EFNL treatment caused downregulation of anti-apoptotic (Bcl-2), angiogenic proteins (angiopoietin and vascular endothelial growth factor A [VEGF-A]), cell cycle regulatory proteins (cyclin D1, cyclin-dependent kinase 2 [Cdk2], and Cdk4), and pro-survival signals such as NFκB, mitogen-activated protein kinase 1 (MAPK1). The data obtained in this study demonstrate that EFNL exert a potent anticancer effect against mammary tumorigenesis by altering key signaling pathways.

Neem components as potential agents for cancer prevention and treatment

“…Other studies shed light on the potential anti-angiogenic mechanisms of neem components. For example, studies in rat model show that ethanolic fraction of neem leaf downregulates angiogenic protein VEGF-A, thus causing inhibition of angiogenesis in chemical carcinogen-induced mammary tumorigenesis [90]. NLE inhibits migration of human endothelial cells resulting in attenuation of angiogenesis [13].…”

A supercritical CO2 extract of neem leaf (A. indica) and its bioactive liminoid, nimbolide, suppresses colon cancer in preclinical models by modulating pro‐inflammatory pathways

“…Organic solvent extracts of neem leaf have demonstrated antitumor effects in models of breast, prostate, and pancreatic cancer among others. 5,6 Supercritical extract technology allows for better extraction of bioactive principals from natural compounds circumventing lability of active agents to heat or to solvent degradation/ alteration. A supercritical CO 2 extract of neem leaf was used in the current study and this method allows for better retention of innate volatiles.…”

Current Evidence about Neem Extracts, the Molecules and Physiological Mechanisms Their Nutritional Components Interact with

“…Inhibits the progression of mammary tumorigenesis induced by chemical carcinogens in rat models. Highly effective in reducing X [1] the burden of the breast tumor and in suppressing breast tumor progression, even after cessation of treatment. ↑ p53; ↑ Bax; ↑ Bad; ↑ caspases; ↑ PTEN; ↑ JNK; ↓ Bcl-2; ↓ cyclin; D1; ↓ Cdk2; ↓ Cdk4; ↓ MAPK1.…”

“…Over the past several decades, an endless count of medicinal plants and phytochemicals (typically present in the diet) have been studied to determine their anti-cancerous activity [1,4,[46][47][48][49][50][51].…”