Abstract
BackgroundNardostachys jatamansi DC is a Himalayan medicinal herb that has been described in various traditional systems of medicine for its use in cancer. In view of its traditional claims, and chemical constituents, antioxidant and anticancer activities were evaluated in breast carcinoma.MethodsPetroleum ether (NJPE), methanol extract (NJM) and subsequent diethyl ether (NJDE), ethyl acetate (NJEA) and aqueous (NJAQ) fractions of roots and rhizomes of N. jatamansi were prepared. Total phenolic, flavonoid content, and antioxidant activities were determined using suitable methods. Antiproliferative activity was assessed in estrogen receptor (ER)-positive (MCF-7) and ER-negative breast carcinoma (MDA-MB-231) cells by MTT and SRB assay. Cell cycle analysis, Hoechst staining, and clonogenic assay were employed to determine the mode of antiproliferative and pro-apoptotic activity in MDA-MB-231 cells.ResultsNJM/fractions exhibited prominent antioxidant activity with significant correlation between phenolic content and ABTS (IC50) scavenging (R = −0.9680, P < 0.05), and total antioxidant capacity (R = 0.8396, P > 0.05). In MTT assay, NJM exhibited the highest antiproliferative activity (IC50: 58.01 ± 6.13 and 23.83 ± 0.69 μg/mL in MCF-7 and MDA-MB-231 respectively). Among the fractions, NJPE and NJDE were found to be most potent in MCF-7 (IC50: 60.59 ± 4.78 μg/mL) and MDA-MB-231 (IC50: 25.04 ± 0.90 μg/mL) cells respectively. Statistical analyses revealed NJM and NJDE exhibited significantly higher (P < 0.05) cytotoxicity in MDA-MB-231 cells. Cell cycle analysis demonstrated that NJM, NJPE and NJEA caused G2/M arrest while NJDE caused G0/G1 phase arrest in MDA-MB-231 cells. Further, NJM/fractions induced significant (P < 0.001) cell death by apoptosis characterized by apoptotic morphological changes in Hoechst staining and inhibited long-term proliferation (P < 0.001) of MDA-MB-231 cells in clonogenic assay. Lupeol and β-sitosterol were identified as anticancer principles in NJM/fractions by HPTLC.ConclusionOur results suggest that NJM/fractions possess significant antiproliferative potential which is mediated through cell cycle perturbation and pro-apoptotic effects in MDA-MB-231 cells. Moreover, this study highlights the antioxidant potential of NJM/fractions which can be attributed to the presence of phenols. NJDE emerged as the most potent fraction and further mechanistic and phytochemical investigations are under way to identify the active principles.
Highlights
Nardostachys jatamansi DC is a Himalayan medicinal herb that has been described in various traditional systems of medicine for its use in cancer
With the advent of selective estrogen replacement modulators (SERMs) and aromatase inhibitors, there has been a significant impact on morbidity and mortality in estrogen receptor (ER) positive breast cancer ; these drugs pose a number of serious adverse effects like uterine cancer, thromboembolism, cataracts, and perimenopausal symptoms [1,2,3]
Few research groups have evaluated the cytotoxic activity of N. jatamansi extract in various cancer cell lines [23,24,25], the mechanism of action of antiproliferative activity has not been investigated in breast cancer till date
Summary
Nardostachys jatamansi DC is a Himalayan medicinal herb that has been described in various traditional systems of medicine for its use in cancer. Cancer cell populations lose their ability to negatively regulate cell cycle leading to uncontrolled cellular proliferation and acquire the potential to evade apoptosis diminished cell attrition [5]. These are two of the most important factors that are conducive to cancer progression. Since apoptosis and cell cycle arrest are essentially involved in neoplastic transformation and metastases, activation of apoptotic pathways and negative regulation of cell cycle progression in cancer cells are considered to be valuable therapeutic approaches for cancer treatment
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