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  1. Chaudhry GE, Islamiah M, Zafar MN, Bakar K, Aziz N, Saidin J, et al.
    Asian Pac J Cancer Prev, 2021 May 01;22(5):1365-1373.
    PMID: 34048163 DOI: 10.31557/APJCP.2021.22.5.1365
    Cancer is an uncontrolled multiplication of cells. The desire efficacy and severe toxicity of current anticancer drugs urge exploring and investigating a better alternative to existing chemotherapeutics. Natural products of marine origin are excellent sources of potential new drugs of enhanced biological activities.

    OBJECTIVES: Thus, the cytotoxic effects along with investigating the mode of cell death exerted by fractions, AP-9, AP-THR, DS-8 and DS-9 fraction of Acanthaster planci, Diadema setosum sp., on the human cervical cancer cell line, HeLa.

    METHODS: The cytotoxicity of fractions has determined by using an MTS assay. The early and late apoptosis was studied by using the High content Screening (HCS) instrument.

    RESULTS: The four fractions produced effective cytotoxicity effects with IC50 values at 72hr of less than 20 μg/ml in the order of AP-9 > DS-9 > APTHR-9 > DS-8. The fraction s exhibited cytotoxicity via mediating apoptotic mode of cell death. The early apoptosis by exposure of phosphatidylserine to the outer leaflet of the plasma membrane and late apoptosis due to the presence of green stain (DNA fragmentation) in treated cells.

    CONCLUSION: The potent bioactive compounds might be responsible for inducing apoptosis in cancer cells and, thus, the potential to be a successful candidate for exploring upcoming chemotherapeutic drugs.

    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  2. Sivanesaratnam V
    Ann Acad Med Singap, 1998 Sep;27(5):622-6.
    PMID: 9919328
    Although the primary operative mortality following radical hysterectomy for stage IB and early stage IIA cervical carcinoma is less than 1%, survival is poor in those patients with histological evidence of "risk" features--lymph node metastases, lymphatic vascular tumour permeation and clinically undetected parametrial metastases. In the 7-year period 1983 to 1989, 239 patients with stage IB and early IIA disease had radical hysterectomy and pelvic lymphadenectomy. One hundred and eight patients (45.2%) had various poor prognostic histological features and received adjuvant chemotherapy--70 had cisplatin, vinblastine, bleomycin (PVB), 16 had mitomycin C (MMC) and 22 others received mitomycin C + 5-fluorouracil (5-FU). Although not randomised, the risk factors present in each group were identical. These patients have now been followed up for periods ranging from 8 to 14 years. All recurrences, except one, occurred within 23 months of surgery; in the remaining this occurred 8 years later. This suggests that very close long-term follow-up is needed. Recurrences were markedly higher in the group who refused adjuvant chemotherapy (31.6%). The 10-year survival in patients without risk factors was 97.2%. In those patients with risk factors refusing adjuvant therapy it was 73.7%. The adjuvant chemotherapy group had a better survival of 86.1% (P = 0.001). The 10-year survivals in patients with positive nodes were similar--66.7% in the MMC group and 71.4% in the PVB group. The 10-year survival in patients with squamous cell carcinoma was significantly better (90.3%) in the mitomycin C (and MMC + 5-FU) group compared to the PVB group (80.1%) (P = 0.005). The 10-year survival in patients with adenocarcinoma and adenosquamous carcinoma was significantly better (96.3%) in the PVB group compared to those receiving MMC (and MMC + 5-FU) (57.1%) (P = 0.01). It would, thus, appear that the adjuvant chemotherapy of choice for patients with squamous cell carcinoma would be MMC (and MMC + 5-FU) and for those with adenocarcinoma, the PVB regime.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  3. Sivanesaratnam V, Sen DK, Jayalakshmi P
    Aust N Z J Obstet Gynaecol, 1987 Aug;27(3):231-3.
    PMID: 2449159
    Patients at high risk of recurrence or metastases following radical surgery for Stage 1B and 2A cervical carcinoma include those with pelvic node metastases, lymphatic or vascular space permeation in the cervix by tumour cells, large size of the primary tumour, involvement of the full thickness of the cervix and parametrial spread. We report the initial results of adjuvant chemotherapy using a combination of cisplatinum, bleomycin and vinblastine in 22 patients who had undergone Wertheim radical hysterectomy and were thought to be at high risk of developing recurrence. The mean duration of follow-up was 23 months. All are alive after follow-up ranging from 13 to 43 months. Three patients developed recurrences--one in the pelvis, another at the posterior aspect of the urethral meatus and the third developed pulmonary secondaries at 20 to 23 months after surgery. Toxicity from the chemotherapy was acceptable.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  4. Sul ‘ain MD, Zakaria F, Johan MF
    Asian Pac J Cancer Prev, 2019 Jan 25;20(1):185-192.
    PMID: 30678430
    Background: Cervical cancer is one of the most commonly diagnosed neoplasms and a leading cause of cancer
    death among females worldwide. Limitations with conventional medical treatments have driven researchers to
    search for alternative approaches using natural products. This study aimed to detemine potential anti-proliferative
    effects of methanol and water extracts of Pyrrosia piloselloides (P. piloselloides) on the HeLa cell line. Methods:
    3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to determine IC50
    concentrations and apoptosis analysis was by flow cytometry. To identify chemical compounds in the extracts, gas
    chromatography-mass spectrometry (GC-MS) was employed. Results: P. piloselloides methanol extracts (PPME) showed
    antiproliferative effects on HeL awith an IC50 of 16.25μg/mL while the P. piloselloides water extract (PPWE) was without
    influence. Neither extract showed any significant effects on apoptosis. GC-MS analysis, revealed 5-hydroxymethylfurfural
    (23.1%), allopurinol (8.66%) and 3, 5-dihydroxy-6-methyl-2,3-dihydropyran-4-one (7.41%) as major components in
    the PPME, while sulfolan-3-ol (10.1%), linoleic acid (9.06%) and β-sitosterol acetate (7.98%) predominated in the
    PPWE case. Conclusion: This first study of P. piloselloides showed PPME to exert potent anti-proliferative effect on
    HeLa cell lines. Further research now needs to be performed to establish the mechanisms of inhibition.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  5. Sivanesaratnam V, Jayalakshmi P, Loo C
    Gynecol Oncol, 1993 Jan;48(1):68-75.
    PMID: 8423024
    The simultaneous occurrence of carcinoma of the cervix in pregnancy is uncommon. In a prospective study of 397 patients undergoing type III radical hysterectomy for early invasive cancer of the cervix, 18 were pregnant at the time of surgery; 4 of these were operated after delivery elsewhere. Two others had a type I extrafascial hysterectomy. The incidence was 1 in 4077 deliveries. The clinical and histological characteristics of these patients are presented. Routine speculum examination and cervical cytology in all pregnant patients early in pregnancy are vital for early diagnosis. Bleeding in pregnancy should not automatically be assumed to be caused by pregnancy-related conditions. The strategies in surgical management are discussed. Radical hysterectomy in pregnancy is safe. No major complications were encountered; the mean blood loss was 1.4 liters. The incidence of pelvic node metastases was similar to that seen in nonpregnant patients. The overall 5-year survival rate was 77.7%. Of the 4 patients who died, 3 presented in the puerperium; all succumbed within 27 months. Poor histological prognostic features contributed to the significantly poorer survival in the puerperal patients (P = 0.0445). The 5-year survival in those presenting during the antepartum period (92.8%) was, however, similar to that in the nonpregnant patients. Metastases to the placenta or fetus were not encountered.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy
  6. Abdelwahab SI, Abdul AB, Zain ZN, Hadi AH
    Int Immunopharmacol, 2012 Apr;12(4):594-602.
    PMID: 22330084 DOI: 10.1016/j.intimp.2012.01.014
    Interleukin-6 is one of the factors affecting sensitivity to cytotoxic agents. Therefore, the current study was designed to investigate the role of IL-6 and IL6 receptors in the cytotoxic effects of zerumbone in ovarian and cervical cancer cell lines (Caov-3 and HeLa, respectively). Exposure of both cancer cells to zerumbone or cisplatin demonstrated growth inhibition at a dose-dependent manner as determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,Sdiphenyltetrazolium bromide) reduction assay. Both laser scanning confocal microscopy and TUNEL assay showed typical apoptotic features in treated cells. The studies conducted seems to suggest that zerumbone induces cell death by stimulating apoptosis better than cisplatin, based on the significantly higher percentage of apoptotic cells in zerumbone's treated cancer cells as compared to cisplatin. In addition, zerumbone and cisplatin arrest cancer cells at G2/M phase as analyzed by flow cytometry. Our results indicated that zerumbone significantly decreased the levels of IL-6 secreted by both cancer cells. In contrast, HeLa and Caov-3 cells were still sensitive to cisplatin and zerumbone, even in the presence of exogenous IL-6. However, membrane-bound IL-6 receptor is still intact after zerumbone treatment as demonstrated using an immune-fluorescence technique. This study concludes that the compound, zerumbone inhibits both cancer cell growth through the induction of apoptosis, arrests cell cycle at G2/M phase and inhibits the secretion levels of IL-6 in both cancer cells. Therefore, zerumbone is a potential candidate as a useful chemotherapeutic agent in treating both cervical and ovarian cancers in future.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  7. Mayer AMS, Hall ML, Lach J, Clifford J, Chandrasena K, Canton C, et al.
    Mar Drugs, 2021 Sep 07;19(9).
    PMID: 34564169 DOI: 10.3390/md19090506
    Manzamines are complex polycyclic marine-derived β-carboline alkaloids with reported anticancer, immunostimulatory, anti-inflammatory, antibacterial, antiviral, antimalarial, neuritogenic, hyperlipidemia, and atherosclerosis suppression bioactivities, putatively associated with inhibition of glycogen synthase kinase-3, cyclin-dependent kinase 5, SIX1, and vacuolar ATPases. We hypothesized that additional, yet undiscovered molecular targets might be associated with Manzamine A's (MZA) reported pharmacological properties. We report here, for the first time, that MZA selectively inhibited a 90 kDa ribosomal protein kinase S6 (RSK1) when screened against a panel of 30 protein kinases, while in vitro RSK kinase assays demonstrated a 10-fold selectivity in the potency of MZA against RSK1 versus RSK2. The effect of MZA on inhibiting cellular RSK1 and RSK2 protein expression was validated in SiHa and CaSki human cervical carcinoma cell lines. MZA's differential binding and selectivity toward the two isoforms was also supported by computational docking experiments. Specifically, the RSK1-MZA (N- and C-termini) complexes appear to have stronger interactions and preferable energetics contrary to the RSK2-MZA ones. In addition, our computational strategy suggests that MZA binds to the N-terminal kinase domain of RSK1 rather than the C-terminal domain. RSK is a vertebrate family of cytosolic serine-threonine kinases that act downstream of the ras-ERK1/2 (extracellular-signal-regulated kinase 1/2) pathway, which phosphorylates substrates shown to regulate several cellular processes, including growth, survival, and proliferation. Consequently, our findings have led us to hypothesize that MZA and the currently known manzamine-type alkaloids isolated from several sponge genera may have novel pharmacological properties with unique molecular targets, and MZA provides a new tool for chemical-biology studies involving RSK1.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  8. Karan D, Dubey S, Pirisi L, Nagel A, Pina I, Choo YM, et al.
    J Nat Prod, 2020 Feb 28;83(2):286-295.
    PMID: 32022559 DOI: 10.1021/acs.jnatprod.9b00577
    Natural products remain an important source of drug leads covering unique chemical space and providing significant therapeutic value for the control of cancer and infectious diseases resistant to current drugs. Here, we determined the antiproliferative activity of a natural product manzamine A (1) from an Indo-Pacific sponge following various in vitro cellular assays targeting cervical cancer (C33A, HeLa, SiHa, and CaSki). Our data demonstrated the antiproliferative effects of 1 at relatively low and non-cytotoxic concentrations (up to 4 μM). Mechanistic investigations confirmed that 1 blocked cell cycle progression in SiHa and CaSki cells at G1/S phase and regulated cell cycle-related genes, including restoration of p21 and p53 expression. In apoptotic assays, HeLa cells showed the highest sensitivity to 1 as compared to other cell types (C33A, SiHa, and CaSki). Interestingly, 1 decreased the levels of the oncoprotein SIX1, which is associated with oncogenesis in cervical cancer. To further investigate the structure-activity relationship among manzamine A (1) class with potential antiproliferative activity, molecular networking facilitated the efficient identification, dereplication, and assignment of structures from the manzamine class and revealed the significant potential in the design of optimized molecules for the treatment of cervical cancer. These data suggest that this sponge-derived natural product class warrants further attention regarding the design and development of novel manzamine analogues, which may be efficacious for preventive and therapeutic treatment of cancer. Additionally, this study reveals the significance of protecting fragile marine ecosystems from climate change-induced loss of species diversity.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  9. Adebayo IA, Arsad H, Gagman HA, Ismail NZ, Samian MR
    Asian Pac J Cancer Prev, 2020 May 01;21(5):1247-1252.
    PMID: 32458629 DOI: 10.31557/APJCP.2020.21.5.1247
    BACKGROUND: Recently, nanoparticle synthesis by eco-friendly methods has received tremendous attention due to the method advantages and also because of the application of the nanoparticles in cancer research. Therefore, in this study, we synthesized silver nanoparticles from Detarium microcarpum leaf phytochemicals and evaluated its inhibitory effect on pancreatic and cervical cancer cells.

    MATERIALS AND METHODS: Silver nanoparticles (dAgNps) were synthesized by reacting phytochemicals of D. microcarpum leaves with silver nitrate for 12 hours. Cell viability assay was carried out to investigate the cytotoxic effect of dAgNps on HeLa and PANC-1 cells.

    RESULTS: Scanning electron microscopy (SEM) and transmission electron microscopy(TEM) results revealed the average sizes of dAgNps are 81 nm and 84 nm respectively. The x-ray diffraction (XRD) pattern of dAgNps was similar to that of face centered cubic(fcc) structure of silver as reported by joint committee on powder diffraction standards (JCPDS) and fourier-transform infrared spectroscopy (FTIR) analysis showed that some phytochemicals of D. microcarpum such as polyphenols and flavonoids were likely involved in the reduction of Ag+ to form nanoparticles. Finally, cell viability assay revealed dAgNps inhibited PANC-1 and HeLa cell proliferations with IC50 values of 84 and 31.5 µg/ml respectively.

    CONCLUSION: In conclusion, the synthesized nanoparticles from D. microcarpum leaves (dAgNps) have inhibitory effect on pancreatic and cervical cancer cells.

    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  10. Abdul AB, Abdelwahab SI, Bin Jalinas J, Al-Zubairi AS, Taha MM
    Int. J. Gynecol. Cancer, 2009 Aug;19(6):1004-10.
    PMID: 19820360 DOI: 10.1111/IGC.0b013e3181a83b51
    Recent in vitro and in vivo studies have demonstrated that zerumbone (ZER) possesses anticancer properties. The main objective of this study was to examine the effectiveness of the combination of ZER and cisplatin (CIS) to treat cervical intraepithelial neoplasia (CIN) in vivo. Microculture tetrazolium assay and immunohistochemistry of proliferating cellular nuclear antigen were used to study the antitumor effect of ZER. Prenatally exposed female BALB/c mice were used as a model. The progenies with CIN were injected peritoneally with isotonic sodium chloride solution (positive control), CIS, ZER, and a combination of both compounds. All treated and untreated mice were humanely killed, and serum and cervix were obtained for interleukin 6 analysis and histopathologic studies using hematoxylin and eosin staining, respectively. Zerumbone has revealed an antitumor effect on human cervical cancer cells and downregulates immunoexpression of proliferating cellular nuclear antigen (P < 0.05). In vivo study indicates that ZER at 16 mg/kg and CIS at 10 mg/kg have a regressing effect on CIN. The combination of ZER and CIS also showed similar effectiveness in regressing CIN. Our results indicate that the combination of ZER and CIS has modulated the serum level of interleukin 6 when compared with that in mice treated with isotonic sodium chloride solution (P < 0.05). The effectiveness of combining ZER and CIS could be further explored as a new therapeutic intervention of early precancerous stages of carcinogenesis before the invasive stage begins.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  11. Devi Beena CR, Tang TS, Gerard LC
    Med J Malaysia, 2008 Sep;63 Suppl C:63-5.
    PMID: 19230250
    Carcinoma of the cervix is the most common malignancy in many developing countries. The purpose of this pilot study on cervical cancer patients treated at selected sites in Malaysia is to examine the achievability of collecting information on patients. The data was collected from the medical records of the patients using case report form. The results reveal that more than 90% of the forms had completed data from all sites. The pilot study has demonstrated that it is feasible to register and collect information on cervical cancer patients using the case report forms. Treatment outcome obtained from this data will form the baseline to establish existing clinical practice and will be useful for treating physicians to monitor the treatment outcome and the late complications and with longer followup to measure the disease free and overall survival. In addition, it is an useful tool as the national indicator.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy
  12. Thabethe KR, Adefolaju GA, Hosie MJ
    Biomed Pharmacother, 2015 Apr;71:227-32.
    PMID: 25960241 DOI: 10.1016/j.biopha.2015.03.001
    Cervical cancer is the third most commonly diagnosed cancer globally and it is one of three AIDS defining malignancies. Highly active antiretroviral therapy (HAART) is a combination of three or more antiretroviral drugs and has been shown to play a significant role in reducing the incidence of some AIDS defining malignancies, although its effect on cervical cancer is still unclear. The aim of this study was to investigate the relationship between cervical cancer and HAART. This was achieved by studying the expression of two signalling molecules expressed in cervical cancer; MUC1 and P65. Following the 24-hour treatment of a cervical cancer cell line, HCS-2, with drugs, which are commonly used as part of HAART at their clinical plasma concentrations, real-time qPCR and immunofluorescence were used in order to study gene and protein expression. A one-way ANOVA followed by a Tukey-Kramer post-hoc test was conducted using JMP 11 software on both sets of data. The drug classified as a protease inhibitor (PI) (i.e. LPV/r) reduced MUC1 and P65 gene and protein expression more than the other drug tested. PIs are known to play a significant role in cell death; therefore, the cells were thought to be more susceptible to cell death following treatment with PIs. In conclusion, the drugs used, especially the PI showed some anticancer effects by facilitating cell death through decreased gene and protein expression of MUC1 and P65 and present promising agents for cancer treatment.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  13. Sivanesaratnam V, Jayalakshmi P
    Cancer, 1989 Aug 15;64(4):798-800.
    PMID: 2501019
    Patients undergoing radical surgical treatment for Stage IB and IIA cervical carcinoma are at high risk of developing local recurrence and/or distant metastases when one or more of the following factors are present: presence of metastatic pelvic lymph nodes, a large primary growth, full-thickness tumor invasion of the cervix, clinically undetected parametrial extension, and lymphatic/vascular channel permeation in the cervix by tumor cells. Carcinoma of the cervix appears to be behaving like a systemic disease. Therefore, systemic measures should be considered in its therapy. The authors report the initial experience with the use of mitomycin C as a single agent adjuvant in 16 patients with Stage IB carcinoma of the cervix who had undergone Wertheim radical hysterectomy and were thought to be in this high-risk group. Fourteen of the patients are alive and free of disease after durations of follow-up ranging from 16 to 38 months, the disease-free survival at a median follow-up of 29 months being 87.5%. One patient required discontinuation of adjuvant chemotherapy because of severe marrow toxicity; however, in view of the presence of a multiple risk factors, pelvic irradiation was given instead. She died 13 months later from disseminated disease. A second patient died 6 months later from congestive cardiac failure.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  14. Mohd-Salleh SF, Wan-Ibrahim WS, Ismail N
    Nutr Cancer, 2020;72(5):826-834.
    PMID: 31433251 DOI: 10.1080/01635581.2019.1654530
    Introduction:Pereskia bleo is a leafy and edible plant, locally known as "Pokok Jarum Tujuh Bilah" which has anticancer properties. This study purposed to determine the cytotoxic effects of P. bleo leaves extracts on several well-known cancer cells and elucidate its underlying mechanism in inducing cell death.Methods: Cytotoxic activity on selected cell lines was determined using MTT assay. Mechanism of cell death was investigated through cell cycle and Annexin V assay. Expression of apoptotic proteins was measured by flow cytometry method.Results: Ethyl acetate extract of P. bleo leaves (PBEA) appeared to have the strongest IC50 value (14.37 ± 8.40 μg/ml) and most active against HeLa cells was further studied for apoptosis. The cell cycle investigation by flow cytometry evidenced the increment of PBEA treated HeLa cells in G0/G1 phase and apoptotic event was detected in Annexin V assay. Analysis of apoptotic protein showed pro-apoptotic proteins (Bax, p53 and caspase 3) were triggered where as anti-apoptotic protein Bcl-2 was suppressed in treated HeLa cells.Conclusions: Our findings demonstrated that PBEA treatment induced cell death in HeLa cells by p53-mediated mechanism through arresting cell cycle at G0/G1 phase and mitochondrial-mediated pathway with involvement of pro-apoptotic proteins, anti-apoptotic protein, and caspase 3.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  15. Ab Hamid S, Wastie ML
    Singapore Med J, 2008 Mar;49(3):e73-5.
    PMID: 18362991
    We report a 43-year-old woman who presented with post-coital bleeding. Pelvic examination revealed a uterine cervical mass, which confirmed to be large B cell lymphoma on histopathological examination. Computed tomography showed a primary lesion in the uterine cervix with no lymph node or other extranodal involvement. The patient responded to CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) chemotherapy regime with no major side effects.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy
  16. Ng WK, Yazan LS, Ismail M
    Toxicol In Vitro, 2011 Oct;25(7):1392-8.
    PMID: 21609759 DOI: 10.1016/j.tiv.2011.04.030
    Thymoquinone (TQ), the active constituent of Nigella sativa or black cumin exhibited cytotoxic effects in several cancer cell lines. In this study, the cytotoxicity of TQ in human cervical squamous carcinoma cells (SiHa) was investigated. TQ was cytotoxic towards SiHa cells with IC50 values of 10.67 ± 0.12 and 9.33 ± 0.19 μg/mL as determined by MTT assay and trypan blue dye exclusion test, respectively, after 72 h of incubation. TQ was more cytotoxic towards SiHa cells compared to cisplatin. Interestingly, TQ was less cytotoxic towards the normal cells (3T3-L1 and Vero). Cell cycle analysis performed by flowcytometer showed a significant increase in the accumulation of TQ-treated cells at sub-G1 phase, indicating induction of apoptosis by the compound. Apoptosis induction by TQ was further confirmed by Annexin V/PI and AO/PI staining. Significant elevation of p53 and down-regulation of the anti-apoptotic Bcl-2 protein was found in the treated cells, without any changes in the expression of the pro-apoptotic Bax protein. In conclusion, thymoquinone from N. sativa was more potent than cisplatin in elimination of SiHa cells via apoptosis with down-regulation of Bcl-2 protein.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  17. Yeap SK, Abu N, Akthar N, Ho WY, Ky H, Tan SW, et al.
    Integr Cancer Ther, 2017 09;16(3):373-384.
    PMID: 27458249 DOI: 10.1177/1534735416660383
    Flavokawain B (FKB) is known to possess promising anticancer abilities. This is demonstrated in various cancer cell lines including HeLa cells. Cervical cancer is among the most widely diagnosed cancer among women today. Though FKB has been shown to be effective in treating cancer cells, the exact molecular mechanism is still unknown. This study is aimed at understanding the effects of FKB on HeLa cells using a microarray-based mRNA expression profiling and proteome profiling of stress-related proteins. The results of this study suggest that FKB induced cell death through p21-mediated cell cycle arrest and activation of p38. However, concurrent activation of antioxidant-related pathways and iron sequestration pathway followed by activation of ER-resident stress proteins clearly indicate that FKB failed to induce apoptosis in HeLa cells via oxidative stress. This effect implies that the protection of HeLa cells by FKB from H2O2-induced cell death is via neutralization of reactive oxygen species.
    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
  18. Teoh PL, Cheng AY, Liau M, Lem FF, Kaling GP, Chua FN, et al.
    Pharm Biol, 2017 Dec;55(1):394-401.
    PMID: 27931178
    CONTEXT: Clinacanthus nutans Lindau (Acanthaceae) is a medicinal plant that has been reported to have anti-inflammatory, antiviral, antimicrobial and antivenom activities. In Malaysia, it has been widely claimed to be effective in various cancer treatments but scientific evidence is lacking.

    OBJECTIVE: This study investigates the chemical constituents, anti-proliferative, and apoptotic properties of C. nutans root extracts.

    MATERIALS AND METHODS: The roots were subjected to solvent extraction using methanol and ethyl acetate. The anti-proliferative effects of root extracts were tested at the concentrations of 10 to 50 μg/mL on MCF-7 and HeLa by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay for 72 h. Morphological changes were observed under light microscope. Pro-apoptotic effects of root extracts were examined using flow cytometric analysis and RT-PCR. The chemical compositions of root extracts were detected using GC-MS.

    RESULTS: The proliferation of MCF-7 cells was inhibited with the IC50 values of 35 and 30 μg/mL, respectively, for methanol and ethyl acetate root extracts. The average inhibition of HeLa cells was ∼25%. Induction of apoptosis in MCF-7 was supported by chromatin condensation, down-regulation of BCL2 and unaltered expression of BAX. However, only ethyl acetate extract caused the loss of mitochondrial membrane potential. GC-MS analysis revealed the roots extracts were rich with terpenoids and phytosterols.

    DISCUSSION AND CONCLUSIONS: The results demonstrated that root extracts promote apoptosis by suppressing BCL2 via mitochondria-dependent or independent manner. The identified compounds might work solely or cooperatively in regulating apoptosis. However, further studies are required to address this.

    Matched MeSH terms: Uterine Cervical Neoplasms/drug therapy*
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