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 Table of Contents  
REVIEW ARTICLE
Year : 2021  |  Volume : 5  |  Issue : 3  |  Page : 252-259

Nanocurcumin: Potential natural alkaloid against oral squamous cell carcinoma


1 Department of Oral Pathology, Faculty of Dental Sciences, Sri Ramachandra Institution of Higher Education and Research, Chennai, Tamil Nadu, India
2 Department of Biomedical Sciences, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institution of Higher Education and Research, Chennai, Tamil Nadu, India

Date of Submission25-May-2021
Date of Acceptance20-Jul-2021
Date of Web Publication7-Sep-2021

Correspondence Address:
Thamizhchelvan Harikrishnan
Department of Oral Pathology, Faculty of Dental Sciences, Sri Ramachandra Institution of Higher Education and Research, Chennai - 600 116, Tamil Nadu
India
Prof. Venkatachalam Deepa Parvathi
Department of Biomedical Sciences, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institution of Higher Education and Research, Chennai - 600 116, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/bbrj.bbrj_102_21

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  Abstract 


Oral cancer has high mortality and morbidity. The traditional treatment of oral squamous cell carcinoma (OSCC) is often a combination of surgery, chemotherapy, and radiation. Curcumin is a natural alkaloid used for centuries against various ailments including cancer. Nanotechnology has its profound application in the diagnosis/prognosis and for therapeutics in cancer. In therapeutics, nanotechnology can convey site-specific delivery of pharmaceutical agents by conferring new properties to the agents and only targeting the drugs to the tumor site, thus reducing systemic toxicity. The encapsulation of curcumin into polymeric nanoparticles seems to be beneficial, since it allows the administration of curcumin hydrophobic drug as an aqueous dispersion. Curcumin reports to inhibit cell proliferation and apoptosis in head-and-neck squamous cell carcinoma and suppresses OSCC cell growth. Most research studies conducted have focused on the anticancer properties of bulk curcumin and its application in adjuvant therapy. The challenge that bulk curcumin poses in terms of its limited uptake and permeability into tissues cannot be ruled out. The possible efficacy of nanocurcumin its effects on OSCC cell line has not been explored adequately. This study aims to review and assess the efficacy of nanocurcumin and its potential as a natural alkaloid against OSCC.

Keywords: Drug-targeted therapy, nanocurcumin, nanomedicine, nanotechnology, oral cancer treatment


How to cite this article:
Khodabux RJ, Parvathi VD, Harikrishnan T. Nanocurcumin: Potential natural alkaloid against oral squamous cell carcinoma. Biomed Biotechnol Res J 2021;5:252-9

How to cite this URL:
Khodabux RJ, Parvathi VD, Harikrishnan T. Nanocurcumin: Potential natural alkaloid against oral squamous cell carcinoma. Biomed Biotechnol Res J [serial online] 2021 [cited 2021 Dec 1];5:252-9. Available from: https://www.bmbtrj.org/text.asp?2021/5/3/252/325602




  Introduction Top


The head-and-neck tumors that arise from the oral cavity are majorly oral and oropharyngeal cancers. Oral cancer (OC) constitutes approximately 5% of all cancers globally and is a leading cause of death due to an oral disease.[1] In India, it is one of the top three types of cancer with 60,000 new cases of OC reported every year.[1] Based on the International Classification of Diseases coding scheme and WHO, OC is the 8th most frequent type of cancer in the world among males and 14th among females.[2] OC has a predilection for the elderly, as most of the cases occur between 50 and 70 years of age, however, recent reports suggest that OC occurs in children as early as 10 years of age, with the absence of any known risk factors.[3] The etiology of OC is multifactorial, tobacco being the most common causative agent.[4],[5] OC can be malignant, and majority (84%–97%) of the OCs are oral squamous cell carcinomas (OSCCs).[6] The treatment of OSCCs is combinatorial including treatment by surgery, chemotherapy, and radiotherapy. Unfortunately, 50% of the patients cannot complete these treatments due to toxicity.

Curcumin (diferuloylmethane) is a phytophenol pigment extracted from the rhizome of Curcuma longa (turmeric) which possesses diverse pharmacological properties. Curcumin acts as an antimicrobial, antioxidant, antifibrosis, anticarcinogenic, anti-inflammatory, and antidiabetic as shown in [Figure 1].[7],[8]
Figure 1: Pharmacological actions of curcumin[9],[10],[11],[12],[13]

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Curcumin exhibits its anti-inflammatory property (by disrupting cell signal transduction) and its antineoplastic property (by inhibition of tumor cell proliferation). Curcumin is known to have a therapeutic role in cancer, including OC by sensitizing tumors to different chemotherapeutic agents. Curcumin through its various modulatory effects has known to play a key role in hematological, gastrointestinal, genitourinary, thoracic, and head-and-neck cancers.[14] Caspase activation, induction of p53/p21 pathway, mitochondrial activation are just few of the many pathways through which curcumin exhibits its apoptotic activity as given in [Table 1].[15],[16]
Table 1: Apoptotic and proliferative modulatory effects of curcumin on different cancers types

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  Nanomaterials Top


Nanomaterial constituents are <100 nm in minimum one dimension. They have significant surface effects, size effects, quantum effects and show better performance properties than traditional materials. Commonly used nanocarriers include micelle, gold, silver and carbon-based carriers, liposomes, magnetic nanocarriers, quantum dots, and others. Liposome nanocarriers consist of a nonaqueous core and a lipid bilayer.[17] Metals such as gold, silver, copper are available as nanocarrier formulations. Magnetic nanoparticle (NP) comprises a metal or metal oxide core encapsulated inside a polymer/inorganic material coating that can be functionalized. The coating ensures the stability and biocompatibility of this nanocarrier. Polymeric nanocarriers are a solid polymer-filled core that provides carriage for hydrophobic drugs [Figure 2]. They can be altered by tuning their compositions (organic, inorganic/hybrid), dimension (small, large sizes), shape (sphere, rods, hyper-branched, multilamellar/multilayered structures), and surface properties (functional group, surface charge, PEGylation, coating process, or attachment for targeting molecule).[18] The dental hard tissues, for example, enamel, dentin, and cementum are made out of nanoscale basic units. In this way, it is conceivable to control materials that emulate these structures. Significant application of nanomaterials in dentistry and the current modality is mentioned in [Table 2].[19],[20],[21],[22],[23]
Figure 2: Nanocarriers

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Table 2: Nanomaterial used in dentistry: Application and current modality

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The two approaches to nanotechnology in dentistry are the top-down approach and the bottom-up approach.[24] The top-down approach is the fabrication of device structure through monolithic processing on a nanoscale, and the bottom-up approach involves the fabrication of device structure through the systematic assembly of atoms, molecules, or other basic units of matter.[25],[26] The different nano-based materials employed in dentistry are listed in [Table 3].[25],[26]
Table 3: Top-down and bottom-up approach in dentistry

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  Nanotechnology in Oral Squamous Cell Carcinoma Top


Nanotechnology in cancer can be applied for diagnosis, prognosis and for therapeutics. In therapeutics, nanotechnology can convey site-specific delivery of pharmaceutical agents by conferring new properties to the agents that target the drugs to only the tumor site thus reduces systemic toxicity. Nanotechnology can provide gadgets competent of being sensitive and specific to anatomic, molecular, and biologic imaging, with relatively with low toxicity.[27] These properties of nanostructures make them a more competent tool over the present norm of care. Owing to the high failure rate of radiation therapy in advanced tumors and toxicity of chemotherapeutic agents, nanotechnology provides a replacement tool with therapeutic devices used for drug and gene delivery, photothermal probe, and radiation enhancers.[27] In the chemotherapy of OSCC, nanodrug delivery system can significantly increase the antitumor activity of drugs in drug-resistant strains resistant to chemotherapy and can achieve good curative effect.[28] Successful research of applying nanodrugs on OSCC is mentioned in [Table 4].[29],[30],[31],[32],[33],[34]
Table 4: Various nanoparticle formulations used on oral squamous cell line

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Nanocarries are loaded with a drug or a chemotherapeutic agent and administered to patients with OC. Nanodrug selectively reaches the tumor site, releases the drug or agent into the malignant cell which brings about DNA damage, and programmed cell death as illustrated in [Figure 3].
Figure 3: Drug targeted delivery by nanocarrier for treatment of oral cancer

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  Curcumin-A Nanoapproach Top


Results from studies conducted “hitherto” have shown an adequate potential of nanorange formulations of curcumin. Properties of nanocurcumin are up to par with that of bulk curcumin. The difference of their properties is mentioned in [Table 5].[14],[16],[35]
Table 5: Differences in the properties of bulk and nanocurcumin

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Studies on the effective use of bulk curcumin and its action on cancers of the oral cavity, larynx, and pharynx in the form of oral gel (Curenext) and various mouthwashes (curcumin mouthwash 0.004%, turmeric mouth wash (prepared in the dilution of 400 mg in 80 ml of water) have been initiated in the past.[36],[37] Results of these studies concluded that curcumin had significantly delayed the onset of mucositis, reduced the ulcer size, pain, and erythema.[36],[37] However, only a handful of studies have been done and further investigation through well-defined clinical trials is required to explore the promising effects of nanocurcumin.

Many formulations and research are directed to creating NPs loaded curcumin with chemotherapeutic agents to provide synergistic effect of the agents [Table 6].[31],[33],[38]
Table 6: Nanocurcumin on oral squamous cell carcinomas and its probable outcomes

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Liposomes, polymers, conjugates, cyclodextrin, micelles, conjugates, and dendrimers are just some of the many formulations that have been produced. Studies indicate in OSCC cell line Centre Antoine Lacassagne-27 (CAL-27) that the antitumor activity of curcumin is mediated by inactivation of NOTCH1 nuclear factor-kappa B (NF-kB) signaling.[39] Studies have reported that curcumin inhibited cell proliferation, apoptosis in head-and-neck squamous cell carcinoma (SCC) through the suppression of IκB kinase-mediated NF.[40] Curcumin suppresses OSCC cell growth through the upregulation of certain proteins besides inhibition through NF-kB.[29],[41]

Incorporation of curcumin as mucoadhesive NP has been studied. Curcumin enhances the anticancer effect of chemotherapeutic agents such as cisplatin, paclitaxel, and 5-fluorouracil (5-FU).[42]


  Discussion Top


OSCC accounts for 90% of the cancers of the head-and-neck region.[3] Tongue SCC is a major type of OSCC. The 5-year survival rate of OC is <63%.[43],[44],[45] Even at the present age OSCC poses to be a major health problem with significant mortality and morbidity. The prime line of treatment is surgery followed by a combination of radiotherapy and chemotherapy to destroy the remaining malignant cells. Despite this extensive rationale of treatment, the survival rate of OSCC patients over the past three decades has not improved appreciably due to increase recurrence of malignant cells at tumor sites and metastatic secondaries.

Chemotherapy is the utilization of anticancer medications to cease the continuous growth of cancer cells. The chemotherapeutic drugs, used frequently are cisplatin, docetaxel, paclitaxel, carboplatin, and 5-FU.[29],[31],[46]

The conventional approaches are concomitant with several side effects which could be both temporary and permanent. Side effects resulted due to chemotherapy are shallow immunity, low blood count, diarrhea, mouth sores, hair fall, nausea, and bleeding. To overcome these drawbacks, several natural products offer an encouraging outlook in the treatment of OC.

Among numerous natural products against OC, curcumin stands to be a very potential alkaloid. Curcumin has been used for thousands of years in traditional oriental medicine as a healing agent due to its various natural properties for the treatment of biliary disorders, anorexia, cough, diabetes, wounds, hepatic disorders, rheumatism, sinusitis, etc.[14] Experimental studies both in vivo and in vitro established superior properties of curcumin.[35] Curcumin possesses diverse and multiple molecular pathway for its action in carcinogenesis and tumor formation. The main disadvantages associated with the oral administration of curcumin are high metabolic instability, low water solubility, poor bioavailability, reduced permeability that limits its systemic bioavailability.[47],[48],[49] Oral uptake of curcumin compels it to pass through systemic circulation through first-pass metabolism. Thus, for curcumin to exhibit its therapeutic effects, a person is required to swallow between 12 and 20 g of curcumin every day for the substantial concentrations of curcumin to be met in the body after ingestion.[50] Low solubility in water makes it highly susceptible to opsonization.

The time of drug contact and tumor cells is an important option for the development of drug delivery systems. Hence, attempts have and are being made to improve the activity of curcumin. To accomplish this, nanotechnology is considered as a potential option. Nanocurcumin of submicron size gives it a major advantage, which allows it to reach virtually inaccessible organs. The higher cellular uptake increases the residence time of nanocurcumin within the tumor site which leads to better drug-mucus interaction to improve in situ delivery. Nanocurcumin with positive and negative surface charge potential makes it extremely stable with improved pharmacokinetics and increased half life. In addition, chemotherapeutic agents coupled with natural antioxidants such as curcumin have been proven to be highly effective for drug delivery and selective targeting of tissue.

sA research study on the comparison of the cytotoxic effects of free curcumin versus curcumin-loaded NP coated with chitosan (Cu-NP- Chitosan (CSL)) on OSCC cell lines resulted that the drug concentration of curcumin-loaded NP was significantly more than free curcumin at all exposure times. The study also proved the apoptotic and cytotoxic cell death of the OSCC cell line.[33] Similar results were obtained in another study wherein codelivery of 5-FU and curcumin were administered in a single-phase Nanoemulsion (NE) drug release system across in vitro OC cell system.[30] In addition, changes in expression of proteins Blc2, Bax, P53, and P 21 have clearly established the high induction of apoptosis. A novel study on the nanoformulations of gefitinib (Gef) and curcumin γ-polyglutamic acid (PGA)-Gef/Cur NPs was significant and clearly showed that γ-PGA-Gef/Cur NPs led to higher anticancer activities than that of free Gef/Cur through apoptotic through caspase- and mitochondria-dependent pathways.[38]

Most of the nanoformulations of curcumin are in early stages of clinical trial, and several research is advocated to establish nanocurcumin as a favorable candidate for therapeutic applications.


  Conclusion Top


OC mostly affects that oral epithelial cells may advance into metastasis and even death. Even after extensive research, OSCC is a major public health problem. Chemoprevention is replaced by other novel technologies to overcome their drawbacks. Nanotechnology and its incorporation into treatment of OC have gained importance. Nanoformulations of curcumin for treatment of OSCC have potential scope for research and are a promising agent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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