Abstract
Aquilaria crassna (agarwood) has been used in traditional Asian medicine to treat vomiting, rheumatism, asthma, cough and inflammation. Despite the wide range of ethno-pharmacological use of agarwood, its anti-angiogenic effect has not previously been evaluated through systematic studies. Therefore, the aim of this study was to prepare essential oils extracts from the stem bark of A. crassna native to Malaysia, and determine their anti-proliferative and anti-angiogenic activities. Stem bark samples were extracted with 80% ethanol and hydrodistillation methods. The resulting essential oils from both extraction approaches were subjected for cytotoxic activity using four cancer cell lines and one normal cell line. Hydrodistilled essential oils displayed significant cytotoxic effect against HCT 116 cells with the lowest IC50 value calculated (28.0 ± 1.5 μg/mL). Furthermore, we have investigated the effect of hydrodistilled essential oils (active extract) on angiogenesis in vitro and ex vivo, and found that essential oils directly inhibited tube formation after plating endothelial cells on matrigel. In addition, essential oils caused significant inhibition of microvessels outgrowth of rat aortic ring assay in a dose-dependent manner (P<0.05) with an IC50 (43.13 μg/ml). The GC-MS analysis of the most active extract showed the presence of several potent phytochemicals such as β-caryophyllene, 1-phenanthrenecarboxylic acid, α-caryophyllene, benzenedicarboxylic acid and azulene. It can be concluded that the anti-cancer and anti-angiogenic effects of the essential oils could be due to the synergistic effect of the biologically active phytoconstituents.
Highlights
Cancer is a complex multifaceted group of more than 100 types of diseases characterized by uncontrolled cell growth, local tissue invasion and metastasis
The present study clearly demonstrates that the essential oil extracted from A. crassna using the hydrodistillation method had a remarkable antiproliferative and antiangiogenic properties
We suggest that the essential oils (EOs) of A. crassna and its phytochemical constituent’s exhibits significant activity against colorectal cancer cells through a mechanism that appears to involve apoptosis induction and angiogenesis suppression
Summary
Cancer is a complex multifaceted group of more than 100 types of diseases characterized by uncontrolled cell growth, local tissue invasion and metastasis. Cancer accounts for about 23% of all disease-related deaths in the USA. It is the second most common cause of death after heart disease. While deaths due to heart disease decreased steeply in both older and younger populations in the USA from 1975 through 2002, no appreciable decline in cancer-caused deaths has been observed so far [1]. Increasing complexity and treatment-associated toxicity with nonspecific target of chemotherapy have aggravated the risk of side effects among the cancer patients [2]. There is a great interest in angiogenesis modulators as therapeutics of several angiogenesis related disorders In this context, several natural products that inhibit angiogenesis demonstrate anticancer activities. The plants that are traditionally used for anticancer treatment often have anti-angiogenic properties through multiple interdependent processes these include Artemisia annua (Chinese wormwood), Viscum album (European mistletoe), Curcuma longa (curcumin), Scutellaria baicalensis (Chinese skullcap), resveratrol and proanthocyanidin (grape seed extract), Magnolia officinalis (Chinese magnolia tree), Camellia sinensis (green tea), Ginkgo biloba, quercetin, Poria cocos, Zingiber officinalis (ginger), Panax ginseng, Rabdosia rubescens hora (Rabdosia), and Chinese destagnation herbs [3,4]
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