More than 90% of oral cancers are oral and oropharyngeal squamous cell carcinoma (OSCC). The overall five-year survival rate of OSCC patients is approximately 63%, which is due to the low response rate to current therapeutic drugs.
Nature is a gold-mine for treatment of various diseases, including cancer, which is evident from the fact that the majority of existing anticancer drugs are either natural products or their chemical derivatives. Since ancient times, numerous medicinal plants extracts and their active components have been reported to have potential uses as anticancer agents. Numerous studies have reported that medicinal plants display anticancer and cytotoxic activities. Polyphenols, such as phenolic acids, flavonoids, terpenes, and alkaloids, possess the biological potential of medicinal plants. Furthermore, flavonoids such as Kempherol, myricetin quercetin, and rutin have been reported to display anticancer properties. Additionally, several alkaloids such as matrine and sanguinarine have been reported to possess anticancer activities.
Researchers have identified potential therapeutic compounds for oral cancer based on their corresponding physicochemical properties and cancer specific bioactivity evidences, which include:
Resveratrol is stilbene-class of polyphenol produced in the skins of many edible plants (grapes, peanuts, and berries) as a response to mechanical injury, fungal infection, and u.v. radiation. The highest naturally occurring levels of resveratrol are found in Polygonum cuspidatum (Japanese knotweed), a plant which has been used for hundreds of years in traditional Asian medicine to treat inflammation and other ailments. Concentrations of resveratrol vary markedly between plant species. In blueberries, for example, resveratrol concentrations approximate only 32 ng/g, compared with levels up to 1920 and 3540 ng/g in peanuts and grapes respectively (other beneficial compounds are also present in varying quantities).13 It has shown activity against various cancers, including oral cancer.
Nimbolide is a natural bioactive compound (extracted from neem tree) with a high potential to treat oral cancer. It has been reported to induce apoptosis and inhibit cell proliferation in an animal models.
Luteolin is a natural flavonoid present in carrots, broccoli, onion leaves, parsley, celery, sweet bell peppers, and chrysanthemum flowers. It degrades relatively little during cooking. It has shown activity against various cancers and can reverse multidrug resistance (MDR) in many types of cancer cells.1,14
Phenethyl isothiocyanate is abundantly present in watercress, broccoli and Brussels sprouts, exerts cancer chemopreventive effects in animal models, and studies also support the role of dietary intake in protection against cancer in humans. It has been reported to suppress invasion of oral squamous carcinoma cell.
Aloe emodin is the main bioactive components of rhubarb (Rheum palmatum), which has been used in traditional Chinese medicine. Aloe-emodin is also abundant in the leaves of the common plant Aloe vera. It has been reported to regulate growth of prostate, breast and oral cancer cells.1,15
Quercetin is a bioactive flavonoid, is widely spread in various edible plants, and the primary sources are red onions, apples, and tea; it is active against cancer cell proliferation in various cancers, including human oral squamous cell carcinoma.9
Ellagic acid is a polyphenolic compound present in fruits and berries such as pomegranates, strawberries, raspberries and blackberries. It has anticarcinogenic, antioxidant and antifibrosis properties. The anticarcinogenic effect of ellagic acid was shown in several types of cancers including skin, esophageal, pancreatic, and colon cancers.16
Baicalein is one of the effective ingredients extracted from Scutellaria baicalensis (or Baikal skullcap) which has anti-inflammatory, anti-bacterial, anti-viral, anti-allergy, and anti-tumor properties by inducing the inhibition of cell proliferation in ovarian and gallbladder cancer.16
Berberine is an alkaloid, the main active ingredient of Coptis Root (also known as rhizoma coptidis and Huang Lian) and Cortex Phellodendri bark. It can regulate blood glucose level, reduce blood lipid, provide an effect of antiarrhythmia and antiplatelet aggregation, enhance body immunologic function; it also induces death in colorectal cancer cells.7,8
Genistein is an isoflavonoid, phytoestrogenic compound, the main secondary metabolite of the Trifolium (clover) species and in Glycine max (soybean); best known for its ability to inhibit cancer progression and metastasis, an important mechanism by which it is able to reduce mortality associated with solid organ cancer. This is highly relevant, as solid organ cancer has an extremely poor prognosis once it has progressed to the metastatic stage. Genistein has therefore become one of the most widely studied small-molecule inhibitors of both cancer cell growth and metastasis and has the potential to be of substantial clinical benefit to patients with various types of cancer.6
Stilbenes and pterostilbene are found in grapes and blueberries. Both are active against prostate cancer cells; pterostilbene is a natural potent analog of resveratrol and the primary antioxidant component of blueberries. It was reported to suppress invasion of oral cancer cells by inhibiting the expression of MMP-2.6
Deguelin is an extract from Derris trifoliate that has been reported to be effective in inhibiting the proliferation, metastasis and invasion of various types of tumors (osteosarcoma, human lung SCC).5
Andrographolide is a compound extracted from Andrographis paniculata (Green chiretta), traditional medicinal herb commonly available in Asian countries. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties.4 It is able to control Hepatitis C virus, abnormal growth of vascular smooth muscle cells causing obstructive arterial diseases.
Colchicine is an alkaloid that is considered first-line therapy for treatment of acute gout, prophylaxis of gout, and familial Mediterranean fever. It is also commonly used in other diseases including pseudogout, pericarditis, Behçet’s disease and neutrophilic dermatoses. It has good therapeutic potential when administered to patients with Oral Submucous Fibrosis (pre-cancerous condition of oral mucosa).3
Black tea polyphenols inhibit cell invasion in human tongue squamous carcinoma. Green tea polyphenols inhibit cancer cell growth in oral dysplastic leukoplakia and squamous cell carcinoma.10
Caffeic acid phenethyl ester (CAPE) as an alternative treatment for oral cancer. CAPE is a strong antioxidant extracted from honeybee hive propolis which is produced by honeybees through mixing the secretions of their hypopharyngeal glands with the digested product of resins collected from leaves, flowers, and tree barks). It is used to build honeybee hives. Propolis also acts as a biocide to kill invasive bacteria, fungi, or even larvae. Propolis has been reported to exhibit anti-bacterial, anti-viral, fungicidal, anti-oxidative, free radical scavenging, immuno-modulatory, and anti-cancer activities. Recent studies indicate that CAPE treatment can effectively suppress the proliferation, survival, and metastasis of oral cancer cells.11,12
- Potential Compounds for Oral Cancer Treatment: Resveratrol, Nimbolide, Lovastatin, Bortezomib, Vorinostat, Berberine, Pterostilbene, Deguelin, Andrographolide, and Colchicine. Saurabh Bundela,1,2 Anjana Sharma,2 and Prakash S. Bisen1,3. PLoS One. 2015; 10(11): e0141719.
- The Mitochondria-Mediate Apoptosis of Lepidopteran Cells Induced by Azadirachtin. Jingfei Huang,1 Chaojun Lv,1,2 Meiying Hu,1 and Guohua Zhong1,* PLoS One. 2013; 8(3): e58499.
- Colchicine: Old and New. Anastasia Slobodnick, MD,1,2 Binita Shah, MD, MSCI,1,3 Michael H. Pillinger, MD,1,2,4 and Svetlana Krasnokutsky, MD, MSCI1,2 HHS Author Manuscripts
- Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line
Malabika Banerjee, Subrata Chattopadhyay, Tathagata Choudhuri, Rammohan Bera, Sanjay Kumar, Biswajit Chakraborty, and Samir Kumar Mukherjeecorresponding author J Biomed Sciv.23; 2016
- Deguelin Induces the Apoptosis of Lung Squamous Cell Carcinoma Cells through Regulating the Expression of Galectin-1
Bing Yan,1 Dejian Zhao,2 Yinan Yao,1 Zhang Bao,1 Guohua Lu,1 and Jianying Zhou1 Int J Biol Sciv.12(7); 2016
- Dietary pterostilbene is a novel MTA1-targeted chemopreventive and therapeutic agent in prostate cancer. Swati Dhar,#1 Avinash Kumar,#1 Liangfen Zhang,1,2 Agnes M. Rimando,3 Janice M. Lage,2 Jack R. Lewin,2 Azeddine Atfi,1,4 Xu Zhang,5 and Anait S. Levenson1,2,6 Oncotarget. 2016 Apr 5; 7(14): 18469–18484.
- Inhibition of cancer cell invasion and metastasis by genistein. Janet M. Pavese,1,2 Rebecca L. Farmer,1,2,3 and Raymond C. Bergan corresponding author1,2,3 Springer Open ChoicePMC2933845
- The Therapeutic Effect of Berberine in the Treatment of Nonalcoholic Fatty Liver Disease: A Meta-Analysis
Xiaoyun Wei, 1 Chunyan Wang, 1 Shijun Hao, 1 Haiyan Song, 1 , 2 and Lili Yang 1 , 2 , * Evid Based Complement Alternat Medv.2016; 2016
- Berberine regulates AMP-activated protein kinase signaling pathways and inhibits colon tumorigenesis in mice
Weidong Li,1,2,* Baojin Hua,2 Shakir M. Saud,1 Hongsheng Lin,2 Wei Hou,2 Matthias S. Matter,3 Libin Jia,4 Nancy H. Colburn,1 and Matthew R. Young1 HHS Author Manuscripts
- Quercetin Suppresses the Migration and Invasion in Human Colon Cancer Caco-2 Cells Through Regulating Toll-like Receptor 4/Nuclear Factor-kappa B Pathway
Mingyang Han, Yucheng Song, and Xuedong Zhang Pharmacogn Magv.12(Suppl 2); 2016 May
- Protection of Dietary Polyphenols against Oral Cancer. Yijian Ding,1 Hua Yao,1,* Yanan Yao,1 Leonard Yenwong Fai,2 and Zhuo Zhang2,* Nutrientsv.5(6); 2013 Jun
- Caffeic Acid Phenethyl Ester Is a Potential Therapeutic Agent for Oral Cancer. Ying-Yu Kuo,1,2,3,† Wai-Tim Jim,4,5,6,† Liang-Cheng Su,1,† Chi-Jung Chung,7 Ching-Yu Lin,1 Chieh Huo,1,8 Jen-Chih Tseng,1,3,9 Shih-Han Huang,1,8 Chih-Jen Lai,1 Bo-Chih Chen,1,3,9 Bi-Juan Wang,1,3,9 Tzu-Min Chan,10,11 Hui-Ping Lin,12 Wun-Shaing Wayne Chang,12 Chuang-Rung Chang,2 and Chih-Pin Chuu1,13,14,15,* Int J Mol Sciv.16(5); 2015 May
- Resveratrol and cancer: focus on in vivo evidence. Lindsay G Carter, John A D'Orazio,1 and Kevin J Pearson Society for Endocrinology Open Access
- Molecular targets of luteolin in cancer. Muobarak J. Tuorkeycorresponding author Lippincott Williams & Wilkins Open Access
- Emodin and Aloe-Emodin Suppress Breast Cancer Cell Proliferation through ERα Inhibition. Pao-Hsuan Huang, 1 Chih-Yang Huang, 2 , 3 Mei-Chih Chen, 1 , 4 Yueh-Tsung Lee, 1 , 5 Chia-Herng Yue, 1 , 6 Hsin-Yi Wang, 1 , 7 and Ho Lin 1 Evid Based Complement Alternat Med. 2013; 2013: 376123.
- Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells. Mouad Edderkaoui, Irina Odinokova, Izumi Ohno, Ilya Gukovsky, Vay Liang W Go, Stephen J Pandol, and Anna S Gukovskaya World J Gastroenterolv.14(23); 2008 Jun 21
- Baicalein Inhibits Progression of Gallbladder Cancer Cells by Downregulating ZFX. Tian-Yu Liu et al. PLoS One. 2015; 10(1): e0114851.