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The research for innovative treatments against colon adenocarcinomas is still a great challenge. Acacia catechu Willd. heartwood extract (AC) has health-promoting qualities, especially at gastrointestinal level. This study characterized AC for its catechins content and investigates the apoptotic-enhancing effect in human colorectal adenocarcinoma HT-29 cells, along with its ability to spare healthy tissue. Results showed that AC induced an increase in apoptotic cells and ROS formation, reduction in mitochondria membrane potential as well as increase in caspase-9 and -3 activity. AC did not affect rat ileum and colon rings viability and functionality, suggesting its safe profile toward healthy tissue. The present findings outline the potential of AC for colon cancer treatment.
- Acacia Catechu Willd.
- colorectal cancer
- apoptosis
- HT-29 cells
- ROS
- mitochondria membrane potential
- catechins
- polyphenols
- natural compounds
Colorectal cancer (CRC) is one of the most common causes of tumour deaths worldwide [1]. In Europe, it is the second and the third most common form of cancer for women and men, respectively. Its occurrence and progression depend on multiple issues, among which family, age, gender and personal history constitute the major risk factors [2]. Standard treatments include surgery and chemotherapy. In the latter case, drugs induce DNA damage or initiate multiple signalling pathways, including cell cycle arrest, DNA repair, etc., leading to cancer cell death. The outcome of chemotherapeutic drugs in patients, however, is related to the cancer subtype, and often the effects of cytotoxicity, drug resistance and adverse reactions constitute overwhelming problems [3].
Natural products continue to provide leads for compounds endowed with pharmacological activities, especially those for treating many types of cancer [4]. A recent report highlighted that 49% of the small molecules approved in the area of cancer from the 1940s to 2014 were natural products or novel structures directly derived from them [5]. These compounds have cytotoxic properties owing to many different mechanisms of action, such as the inhibition of tumour cell growth accompanied by the induction of apoptosis, DNA damage, etc. Furthermore, anticancer drugs have greater potential to kill tumour cells if administered in combination with plant-derived compounds, and hopefully have less adverse effects. To explore this possibility, several clinical trials for various cancers were performed, including those for CRC [6].
Acacia catechu Willd. extracts have been used in traditional medicine for the treatment of several diseases. It possesses hepatoprotective, antipyretic, antidiarrheal, hypoglycaemic, anti-inflammatory, immunomodulatory, antinociceptive, antimicrobial, free radical scavenging and antioxidant activities [7][8][9][10]. Moreover, recent studies have demonstrated that Acacia catechu Willd. exerts spasmolytic and antispastic activities in vitro by interacting with calcium channels and muscarinic receptors, without affecting Lactobacilli and Bifidobacteria, the most represented intestinal species, suggesting that it may benefit patients suffering from diarrhoea [11]. Acacia catechu Willd. extract contains high amounts of flavonoids, such as flavan-3-ols, (+)-catechin, (−)-epicatechin, (−)-epicatechin-3-O-gallate and (−)-epigallocatechin-3-O-gallate [12]. These derivatives and related polyphenols possess apoptosis-inducing activity in several cancer cell lines [13]. Thus, this study investigates the effects of a preparation obtained by Acacia catechu Willd. heartwood by decoction (AC) on human colorectal adenocarcinoma HT-29 cell line in order to highlight its potential use in cancer therapy. As the capability of AC to spare the viability and functionality of normal tissue may be of clinical interest, this aspect was also investigated in rat ileum and colon rings. The results showed that AC has potential as an anti-cancer agent, as it exhibits irreversible anti-proliferative effects and induces intrinsic apoptosis, while sparing healthy tissue.
The present study outlines the potential of AC for CRC treatment, as this extract induced cytotoxicity of human colorectal adenocarcinoma HT-29 cells, which was accompanied by increases in apoptotic cells and ROS formation; a reduction in MMP; and increases in caspase-9 and 3 activities. AC did not affect rat ileum and colon rings viability and functionality, suggesting a safe profile toward healthy tissue. Moreover, AC main components are absorbed rapidly and eliminated slowly [14], and this might constitute an added value to the potential use of AC for CRC prevention.
This entry is adapted from the peer-reviewed paper 10.3390/ijms21062102
References
- Nana Keum; Edward Giovannucci; Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nature Reviews Gastroenterology & Hepatology 2019, 16, 713-732, 10.1038/s41575-019-0189-8.
- Matteo Malvezzi; G. Carioli; P. Bertuccio; P. Boffetta; F. Levi; Carlo La Vecchia; E. Negri; European cancer mortality predictions for the year 2018 with focus on colorectal cancer. Annals of Oncology 2018, 29, 1016-1022, 10.1093/annonc/mdy033.
- Tao Xie; Mengxi Huang; Ye Wang; Liya Wang; Cheng Chen; Xiao-Yuan Chu; MicroRNAs as Regulators, Biomarkers and Therapeutic Targets in the Drug Resistance of Colorectal Cancer. Cellular Physiology and Biochemistry 2016, 40, 62-76, 10.1159/000452525.
- Alan L. Harvey; RuAngelie Edrada-Ebel; Ronald J Quinn; The re-emergence of natural products for drug discovery in the genomics era. Nature Reviews Drug Discovery 2015, 14, 111-129, 10.1038/nrd4510.
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- Xuan-Mei Huang; Zhi-Jie Yang; Qing Xie; Zi-Kang Zhang; Hua Zhang; Junying Ma; Natural products for treating colorectal cancer: A mechanistic review.. Biomedicine & Pharmacotherapy 2019, 117, 109142, 10.1016/j.biopha.2019.109142.
- B.P. Burnett; Q. Jia; Y. Zhao; R.M. Levy; A Medicinal Extract ofScutellaria baicalensisandAcacia catechuActs as a Dual Inhibitor of Cyclooxygenase and 5-Lipoxygenase to Reduce Inflammation. Journal of Medicinal Food 2007, 10, 442-451, 10.1089/jmf.2006.255.
- M.A. Sunil; V.S. Sunitha; Radhakrishnan. E.K; M. Jyothis; Immunomodulatory activities of Acacia catechu, a traditional thirst quencher of South India. Journal of Ayurveda and Integrative Medicine 2019, 10, 185-191, 10.1016/j.jaim.2017.10.010.
- Devaraj Ezhilarasan; Thangavelu Lakshmi; Rajagopal Vijayaragavan; Sukhwinder Kaur Bhullar; Ramasamy Rajendran; Acacia catechu ethanolic bark extract induces apoptosis in human oral squamous carcinoma cells. Journal of Advanced Pharmaceutical Technology & Research 2017, 8, 143-149, 10.4103/japtr.japtr_73_17.
- Mohammed Rahmatullah; Maraz Hossain; Arefin Mahmud; Nahida Sultana; Sheikh Mizanur Rahman; Mohammad Rashedul Islam; Mujiba Salma Khatoon; Sharmin Jahan; Fatema Islam; Antihyperglycemic and Antinociceptive Activity Evaluation of ‘Khoyer’ Prepared from Boiling the Wood of Acacia Catechu in Water. African Journal of Traditional, Complementary and Alternative Medicines 2013, 10, 1-5, .
- Matteo Micucci; Roberto Gotti; Ivan Corazza; Gabriella Tocci; Alberto Chiarini; Marta De Giorgio; Luca Camarda; Maria Frosini; Carla Marzetti; Monica Cevenini; et al. Newer Insights into the Antidiarrheal Effects of Acacia catechu Willd. Extract in Guinea Pig. Journal of Medicinal Food 2017, 20, 592-600, 10.1089/jmf.2016.0154.
- Diandian Shen; Qingli Wu; Mingfu Wang; Yonghong Yang; Edmond J. Lavoie; James E. Simon; Determination of the Predominant Catechins inAcacia catechuby Liquid Chromatography/Electrospray Ionization−Mass Spectrometry. Journal of Agricultural and Food Chemistry 2006, 54, 3219-3224, 10.1021/jf0531499.
- Abu Hazafa; Khalil-Ur- Rehman; Nazish Jahan; Zara Jabeen; The Role of Polyphenol (Flavonoids) Compounds in the Treatment of Cancer Cells. Nutrition and Cancer 2019, 72, 386-397, 10.1080/01635581.2019.1637006.
- Libin Wang; Xin Shen; Le Mi; Juan Jing; Shouchang Gai; Xueying Liu; Qingwei Wang; Shengyong Zhang; Simultaneous determinations of four major bioactive components in Acacia catechu (L.f.) Willd and Scutellaria baicalensis Georgi extracts by LC–MS/MS: Application to its herb–herb interactions based on pharmacokinetic, tissue distribution and excretion studies in rats. Phytomedicine 2019, 56, 64-73, 10.1016/j.phymed.2018.09.239.
