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Fulltext Epithelial Dysplasia at Excision Margins of Oral Squamous Cell Carcinoma: A Review on Relationship to Clinicopathological Parameters and Prognosis

Senarath NH, Jayasooriya PR, Siriwardena BSMS, Tilakaratne WM

Asian Pac J Cancer Prev, 2021 Aug 01;22(8):2313-2321.
PMID: 34452541 DOI: 10.31557/APJCP.2021.22.8.2313

BACKGROUND: Epithelial dysplasia (ED) at oral cancer excision margins is a frequent finding. Dysplastic epithelium at excision margins may not be similar to dysplasia in Oral potentially malignant disorders (OPMD) as malignant transformation has already taken place. Therefore, management of ED at excision margins should be different to that of OPMD. ED creates a dilemma in relation to further management of cancer patients, since there are no accepted guidelines. Therefore, the objective of this review is to analyze existing literature and to arrive at evidence based recommendations for the management of ED at excision margins.
METHODS: A comprehensive string was run on PubMed, Medscape and Medline. The final outcome included 113 studies. Finally, the most relevant 10 articles were critically assessed for inclusion and exclusion criteria against various parameters.
RESULTS AND CONCLUSIONS: Severe and Moderate ED need re-excision in order to improve prognosis. There is not enough sound evidence for the management of Mild ED at excision margins of oral squamous cell carcinoma. Guidelines for the management of ED at excision margins should be formulated after comprehensive multi center studies using lager cohorts of patients.
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Matched MeSH terms: Carcinoma, Squamous Cell/pathology*
Cyclooxygenase-2 (COX2) expression in adenocarcinoma surpasses that of squamous cell carcinoma in the uterine cervix

Marutha Muthu AK, Cheah PL, Koh CC, Chew MF, Toh YF, Looi LM

Malays J Pathol, 2017 Dec;39(3):251-255.
PMID: 29279587 MyJurnal

Over the years, adenocarcinoma (ADC), which has a worse prognosis than squamous cell carcinoma (SCC) of the cervix, has shown an increasing trend. Cyclooxygenase-2 (COX2) expression which has been associated with worse prognosis in several solid cancers was studied for its association with SCC and ADC of the cervix. 35 histologically re-confirmed SCC and 35 ADC were immunohistochemically stained for COX2 using a mouse monoclonal antibody to COX2 (1:100; Dako: Clone CX-294) on a Ventana Benchmark XT. The histoscore was computed as intensity of staining, semi-quantitated on a scale of 0-3 with 0 = negative, 1 = weak, 2 = moderate and 3 = strong staining intensity; multiplied by percentage of immunopositivity on a scale of 0-4 with 0 = <1%, 1 = 1-25%, 2 = 26-50%, 3 = 51-75% and 4 = ≥75% of immunopositive tumour cells. Histoscore 1-3/12 was considered as low and ≥4/12 as high COX2 expression. SCC affected Chinese more than Malays, while Malays had more ADC (p = 0.032). Mean age at presentation of SCC (57.5 years) was about a decade later than ADC at 47.9 years (p = 0.002). 30/35 (85.7%) of SCC and 34/35 (97.1%) of ADC expressed COX2. Histoscores of ADC (median = 4.0, IQR = 3.0-6.0) was significantly higher (p = 0.014) than those of SCC (median = 3.0, IQR = 2.0-3.0). High histoscores (≥4/12) were more frequent in ADC (55.9%) compared with SCC (26.7%) (p = 0.018), implicating COX2, either directly or indirectly, as a possible player in influencing the poorer outcome of ADC compared with SCC.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology*
Fulltext Chondrosarcoma of the nasal septum

Indudharan R, Das PK, Azman AA, Suhaiza S

Singapore Med J, 1998 Aug;39(8):376-9.
PMID: 9844502

A case of chondrosarcoma of the nasal septum is presented with the result of treatment. The patient was admitted for a growth in the nose of four years' duration. Fine needle aspiration for cytological examination was suggestive of squamous cell carcinoma. She was treated with lateral rhinotomy and wide excision followed by septorhinoplasty. Histological examination showed that the lesion was chondrosarcoma. The patient remained free of disease 26 months after surgery.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Fulltext World Workshop on Oral Medicine VII: Clinical evidence of differential expression of lncRNAs in oral squamous cell carcinoma: A scoping review

Pentenero M, Bowers LM, Jayasinghe R, Yap T, Cheong SC, Kerr AR, et al.

Oral Dis, 2019 Jun;25 Suppl 1(Suppl 1):88-101.
PMID: 31140697 DOI: 10.1111/odi.13076

BACKGROUND: Long non-coding RNAs (lncRNAs) have important roles in regulating gene expression pertaining to cell proliferation, survival, migration and genomic stability. Dysregulated expression of lncRNAs is implicated in cancer initiation, progression and metastasis.
OBJECTIVES: To explore, map and summarize the extent of evidence from clinical studies investigating the differential expression of lncRNAs in oral/tongue squamous cell carcinoma.
METHODS: PubMed, Scopus and Web of Science were used as search engines. Clinical, full-length, English language studies were included. PRISMA-ScR protocol was used to evaluate and present results. The present scoping review summarizes relationships of the differential expression of lncRNAs with the presence of tumour and with clinicopathological features including survival.
RESULTS: Almost half of the investigated transcripts have been explored in more than one study, yet not always with consistent results. The collected data were also compared to the limited studies investigating oral epithelial dysplasia. Data are not easily comparable, first because of different methods used to define what differential expression is, and second because only a limited number of studies performed multivariate analyses to identify clinicopathological features associated with the differentially expressed lncRNAs.
CONCLUSIONS: Standard methods and more appropriate data analyses are needed in order to achieve reliable results from future studies.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Screening of differential promoter hypermethylated genes in primary oral squamous cell carcinoma

Khor GH, Froemming GR, Zain RB, Abraham MT, Thong KL

Asian Pac J Cancer Prev, 2014;15(20):8957-61.
PMID: 25374236

BACKGROUND: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC).
OBJECTIVES: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR).
MATERIALS AND METHODS: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis.
RESULTS: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status.
CONCLUSIONS: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Fulltext Resection and reconstruction of malignant tumor involving sternum

Faisham WI, Ziyadi MG, Azman WS, Halim AS, Zulmi W, Biswal BM

Med J Malaysia, 2012 Apr;67(2):224-5.
PMID: 22822652 MyJurnal

We present a series of four cases of chest wall tumor, which underwent sternum resection. The methods of resection and reconstruction chest wall defect are discussed and the final outcome highlighted.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Microsatellite instability and loss of heterozygosity in oral squamous cell carcinoma in Malaysian population

Ashazila MJ, Kannan TP, Venkatesh RN, Hoh BP

Oral Oncol, 2011 May;47(5):358-64.
PMID: 21450513 DOI: 10.1016/j.oraloncology.2011.03.005

Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been documented as important events in oral squamous cell carcinoma (OSCC). Five microsatellite markers D3S192, D3S966, D3S647, D3S1228 and D3S659 were selected on chromosome 3p because of high frequency of alterations reported in head and neck squamous cell carcinoma and the involvement of von Hippel Lindau (VHL) at 3p25-26 and the fragile histidine triad (FHIT) at 3p14.2 genes proven in many tumour types. A total of 50 archival tissue samples of OSCC and corresponding normal samples were analyzed for LOH and MSI status. The overall LOH for the markers selected on 3p was 56 out of 189 informative cases (29.6%). The most frequent LOH was identified for the marker D3S966 which was 18/42 (42.8%) of informative cases suggesting the presence of putative tumour suppressor genes (TSGs) in this loci. In this study, high frequency of microsatellite instability was found in D3S966 which was 28.6% of informative cases; this reveals the possibility of mutations of MMR genes in this region. Frequent microsatellite alterations (MA) were observed in 3 markers D3S966 (71.4%), D3S1228 (56.7%) and D3S192 (41.0%). There was no significant association between LOH with gender, tumour stages and differentiation grades. However, there was a significant association between tumour stage and differentiation grades with MSI status in OSCC in Malaysian population with p values of 0.002 and 0.035, respectively. There was also a significant association between MA and differentiation grades (p=0.041).

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Transcriptional profiling of oral squamous cell carcinoma using formalin-fixed paraffin-embedded samples

Saleh A, Zain RB, Hussaini H, Ng F, Tanavde V, Hamid S, et al.

Oral Oncol, 2010 May;46(5):379-86.
PMID: 20371203 DOI: 10.1016/j.oraloncology.2010.02.022

Despite the advances in cancer treatment, the 5-year survival rate for oral cancer has not changed significantly for the past 40 years and still remains among the worst of all anatomic sites. Gene expression microarrays have been used successfully in the identification of genetic alterations in cancer development, however, these have hitherto been limited by the need for specimens with good quality intact RNA. Here, we demonstrated the use of formalin-fixed paraffin-embedded tissues in microarray experiments to identify genes differentially expressed between cancerous and normal oral tissues. Forty-three tissue samples were macrodissected and gene expression analyses were conducted using the Illumina DASL assay. We report RNA yield of 2.4 and 0.8 microg/mm(3) from tumour and normal tissues, respectively and this correlated directly with the tissue volume used for RNA extraction. Using unsupervised hierarchical clustering, distinct gene expression profiles for tumour and normal samples could be generated, and differentially expressed genes could be identified. The majority of these genes were involved in regulation of apoptosis and cell cycle, metastasis and cell adhesion including BCL2A1, BIRC5, MMP1, MMP9 and ITGB4. Representative genes were further validated in independent samples suggesting that these genes may be directly associated with oral cancer development. The ability to conduct microarrays on formalin-fixed paraffin-embedded specimens represents a significant advancement that could open up avenues for finding genes that could be used as prognostication and predictive tools for cancer.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Fulltext Three squamous cell carcinomas of different sites in three years: A mere coincidence?

Azman M, Mohd Yunus MR

Indian J Cancer, 2015 Apr-Jun;52(2):201-2.
PMID: 26853404 DOI: 10.4103/0019-509X.175817
Matched MeSH terms: Carcinoma, Squamous Cell/pathology*
Recent trends in histological pattern of cervical carcinoma among three ethnic groups in Malaysia

Cheah PL, Looi LM, Sivanesaratnam V

J Obstet Gynaecol Res, 1999 Dec;25(6):401-6.
PMID: 10680337

To study the trend of different histological types of cervical carcinoma among the 3 major ethnic groups in Malaysia.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Metastatic lung cancer in pregnancy

Wong CM, Lim KH, Liam CK

Respirology, 2003 Mar;8(1):107-9.
PMID: 12856752

Pregnancy complicated by lung cancer has been rarely reported. The regional incidence of this complex situation is likely to increase in the future and optimal management needs to be established to better deal with this situation. We report two patients with metastatic lung cancer complicating pregnancy to highlight the evaluation and management difficulties associated with this problem and to contribute to the limited information in the literature.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology*
Malignancy in oral lichen planus: a review of a group from the Malaysian population

Yaacob HB, Tan PL, Ngeow WC

J Oral Sci, 2002 Jun;44(2):65-71.
PMID: 12227497

The objective of this study was to determine the socio-demography (age, race and gender) of a group of Malaysian patients who were diagnosed as suffering from oral lichen planus (OLP). The occurrence of malignancy was also investigated. A total of 77 clinical and biopsy records of patients with OLP were studied. Females were affected more than males, with the female to male ratio being 2:1. Middle-aged Indian and Chinese females tend to be affected by OLP when compared with the rest of the population. Only 19 patients returned for further follow-up. One adult Indian female with a six-year history of lichenoid reaction showed the presence of malignancy.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Fulltext Biology and pathological associations of the human papillomaviruses: a review

Cheah PL, Looi LM

Malays J Pathol, 1998 Jun;20(1):1-10.
PMID: 10879257

Historical cottontail rabbit papillomavirus studies raised early indications of a mammalian DNA oncogenic virus. Today, molecular cloning recognises numerous animal and human papillomaviruses (HPVs) and the development of in vitro transformation assays has escalated oncological research in HPVs. Currently, their detection and typing in tissues is usually by Southern blotting, in-situ hybridization and polymerase chain reaction methods. The complete papillomavirus virion constitutes a protein coat (capsid) surrounding a circular, double-stranded DNA organised into coding and non-coding regions. 8 early (E1-E8) open reading frames (ORFs) and 2 late (L1, L2) ORFs have been identified in the coding region of all papillomaviruses. The early ORFs encode proteins which interact with the host genome to produce new viral DNA while late ORFs are activated only after viral DNA replication and encode for viral capsid proteins. All papillomaviruses are obligatory intranuclear organisms with specific tropism for keratinocytes. Three possible courses of events can follow papillomaviruses entry into cells: (1) viral DNA are maintained as intranuclear, extrachromosomal, circular DNA episomes, which replicates synchronously with the host cell, establishing a latent infection; (2) conversion from latent into productive infection with assembly of complete infective virions; (3) integration of viral DNA into host cellular genome, a phenomenon seen in HPV infections associated with malignant transformation. Human papillomaviruses (HPVs) essentially induce skin and mucosal epithelial lesions. Various skin warts are well known to be HPV-associated (HPVs 1, 2, 3, 7 and 10). Besides HPVs 3 and 10, HPVs 5, 8, 17 and 20 have been recovered from Epidermodysplasia verruciformis lesions. Anogenital condyloma acuminatum, strongly linked with HPVs 6 and 11 are probably sexually transmitted. The same HPVs, demonstrable in recurrent juvenile laryngeal papillomas, are probably transmitted by passage through an infected birth canal. HPVs described in uterine cervical lesions are generally categorized into those associated with high (16, 18), intermediate (31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68) and low (6, 11, 26, 40, 42, 43, 44, 53, 54, 55, 62, 66) risk of cervical squamous carcinoma. Cervical adenocarcinoma, clear cell carcinoma and small cell neuroendocrine carcinoma have also been linked to HPVs, especially HPV18. Other lesions reported to be HPV-associated are: papillomas, dysplasia and carcinomas in the nasal cavity (HPV 6, 11, 57); squamous papilloma, condyloma acuminatum, and verruca vulgaris of the oral cavity (HPV 6, 11), oral focal epithelial hyperplasia (HPV 13, 32); warty lip lesions (HPV 2): and conjunctival papillomas (HPV 6, 11).

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Proliferating cell nuclear antigen (PCNA) expression in oral squamous cell carcinoma - an aid to conventional histological grading?

Zain RB, Sakamoto F, Shrestha P, Mori M

Malays J Pathol, 1995 Jun;17(1):23-30.
PMID: 8907001

Proliferating cell nuclear antigen (PCNA) is a well known marker for cell proliferation. It tends to accumulate in the late G1 and S-phase of the cell cycle. A monoclonal antibody (MoAb) against PCNA is now available and it can react with paraffin-embedded specimens. In the present study, PCNA immunohistochemical staining of 36 cases of oral cancer specimens obtained from surgery were investigated. The results showed differing nuclear staining patterns for PCNA in normal, hyperplastic and dysplastic epithelium, early cancer and 3 levels of differentiation for squamous cell carcinoma of the oral cavity. It appears that PCNA can be a useful marker in delineating normal epithelium and hyperplastic epithelium from dysplasia in the oral cavity. The use of PCNA staining may further emphasize the conventional histopathological grading of well-differentiated, moderately-differentiated and poorly-differentiated oral squamous cell carcinoma but is still dependent on basic criteria as observed without immunostaining. PCNA expression for all grades of squamous cell carcinoma are present at the deep, infiltrative margins.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Translational genomics and recent advances in oral squamous cell carcinoma

Chai AWY, Lim KP, Cheong SC

Semin Cancer Biol, 2020 04;61:71-83.
PMID: 31542510 DOI: 10.1016/j.semcancer.2019.09.011

Oral squamous cell carcinomas (OSCC) are a heterogeneous group of cancers arising from the mucosal lining of the oral cavity. A majority of these cancers are associated with lifestyle risk habits including smoking, excessive alcohol consumption and betel quid chewing. Cetuximab, targeting the epidermal growth factor receptor was approved for the treatment of OSCC in 2006, and remains the only molecular targeted therapy available for OSCC. Here, we reviewed the current findings from genomic analyses of OSCC and discuss how these studies inform on the biological mechanisms underlying OSCC. Exome sequencing revealed that the significantly mutated genes are mainly tumour suppressors. Mutations in FAT1, CASP8, CDKN2A, and NOTCH1 are more frequently found in OSCC when compared to non-OSCC head and neck cancers and other squamous cell carcinomas, and HRAS and PIK3CA are the only significantly mutated oncogenes. The distribution of these mutations also differs in populations with distinct risk habits. Gene expression-based molecular classification showed that OSCC can be divided into distinct subtypes and these have a preferential response to different types of therapies, suggesting that these classifications could have clinical implications. More recently, with the approval of checkpoint inhibitors for the treatment of cancers including OSCC, genomics studies also dissected the genetic signatures of the immune compartment to delineate immune-active and -exhausted subtypes that could inform on the immune status of OSCC patients and guide the development of novel therapies to improve response to immunotherapy. Taken together, genomics studies are informing on the biology of both the epithelial and stromal compartments underlying OSCC development, and we discuss the opportunities and challenges in using these to derive clinical benefit for OSCC patients.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Fulltext Pathological transition as the arising mechanism for drug resistance in lung cancer

Chen Y, Tang WY, Tong X, Ji H

Cancer Commun (Lond), 2019 10 01;39(1):53.
PMID: 31570104 DOI: 10.1186/s40880-019-0402-8

Despite the tremendous efforts for improving therapeutics of lung cancer patients, its prognosis remains disappointing. This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insufficient development of effective therapeutics in clinic. Based on the current progresses of lung cancer research, we classify drug resistance mechanisms into three different levels: molecular, cellular and pathological level. All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic. Our understanding on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis. In this review, we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
ADAM9 Expression in Uterine Cervical Cancer and Its Associated Factors

Mohd Isa SA, Md Salleh MS, Ismail MP, Hairon SM

Asian Pac J Cancer Prev, 2019 Apr 29;20(4):1081-1087.
PMID: 31030477

Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most
common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane
degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted
therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the
factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital
Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides
obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The
ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done
using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with
ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed
positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was
the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association
with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval
[CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological
type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion:
The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a
prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).

Matched MeSH terms: Carcinoma, Squamous Cell/pathology*
Over-expression of MAGED4B increases cell migration and growth in oral squamous cell carcinoma and is associated with poor disease outcome

Chong CE, Lim KP, Gan CP, Marsh CA, Zain RB, Abraham MT, et al.

Cancer Lett, 2012 Aug 1;321(1):18-26.
PMID: 22459352 DOI: 10.1016/j.canlet.2012.03.025

MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo, and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology*
Fulltext Incidence of nasopharyngeal carcinoma in Malaysia, with special reference to the state of Selangor

Armstrong RW, Kutty MK, Dharmalingam SK

Br. J. Cancer, 1974 Jul;30(1):86-94.
PMID: 4413823

A "registry" of all known cases of nasopharyngeal carcinoma in Malaysia, 1968-72, was established. Attention was focused on the State of Selangor where conditions are best for case finding. Age-adjusted incidence rates among Chinese males and females were 17·3 and 7·3 per 100,000; among Malay males and females, the rates were 2·5 and 0·3 and among Indian males, 1·1. The detailed ethnicity of 192 cases in Selangor was established. Estimated incidence rates for the Chinese sub-groups agreed with the pattern observed elsewhere: highest among the Cantonese, lowest among the Hokkien/Teochiu, with the Khek in between. There was no correlation between histological type and sub-ethnic group among the Chinese cases.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology
Effects of Damnacanthal and Nordamnacanthal on Proliferation, Apoptosis, and Migration of Oral Squamous Cell Carcinoma Cells

Shaghayegh G, Alabsi AM, Ali-Saeed R, Ali AM, Vincent-Chong VK, Ismail NH, et al.

Asian Pac J Cancer Prev, 2017 Dec 29;18(12):3333-3341.
PMID: 29286228

Cancer is one of the most common causes of death in the developed world, with one-third of people diagnosed with
cancer during their lifetime. Oral cancer commonly occurs involving the buccal mucosa (cheeks), tongue, floor of the
mouth and lip. It is one of the most devastating and disfiguring of malignancies. Morinda citrifolia L., commonly known
as ‘noni’, belongs to the Rubiaceae family. It is native to the Pacific islands, Hawaii, Caribbean, Asia and Australia.
The plant displays broad curative effects in pharmacological studies. Damnacanthal (DAM) and Nordamnacanthal
(NDAM), anthraquinone compounds isolated from the roots of Morinda citrifolia L., has been used for the treatment
of several chronic diseases including cancer. The objectives of this study were to evaluate cytotoxicity, morphological
changes, cell death mode (apoptosis/necrosis), and cell migration induced by DAM and NDAM on the most common
type of oral cancer, oral squamous cell carcinoma (OSCC)cells. Anti-proliferative effects of these compounds against
OSCC cell lines were determined by MTT assay. The mode of cell death was analysed by phase contrast and fluorescent
microscopy as well as flow cytometry. In addition, cell migration was assessed. The results showed that DAM and
NDAM exerted cytotoxicity against OSCC cells with IC50 values of 1.9 to >30 μg/ml after 72 h treatment. Maximum
growth inhibition among the tested cell lines for both compounds was observed in H400 cells, and thus it was selected
for further study. The study demonstrated inhibition of H400 OSCC cell proliferation, marked apoptotic morphological
changes, induction of early apoptosis, and inhibition of cell migration by DAM and NDAM. Therefore, this information
suggests that these compounds from noni have potential for used as anti tumor agents for oral cancer therapy.

Matched MeSH terms: Carcinoma, Squamous Cell/pathology*

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