Displaying publications 1 - 20 of 48 in total

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  1. Pulikkotil SJ, Nath S, Ramachandran V
    Community Dent Health, 2020 Feb 27;37(1):26-31.
    PMID: 32031346 DOI: 10.1922/CDH_4632Pulikkotil06
    OBJECTIVES: Identify the determinants of periodontitis in a rural Indian population aged 35-44 years.

    BASIC RESEARCH DESIGN: Case-control clinical and questionnaire study in a cluster sample of 50 villages.

    METHODS: A total of 3000 persons were screened for the presence of periodontitis using the CDC case definition in full mouth examination. Equal numbers of cases (604 persons with periodontitis) and controls (604 without periodontitis) were recruited and interviewed with a piloted questionnaire. Univariate and multivariate analysis estimated crude and adjusted odds ratios (aOR) respectively with 95% confidence limits.

    RESULTS: Six factors were determined by multivariate analysis to predict periodontitis: education less than or equal to twelve years of schooling (aOR=2.51, 95% CI=1.18-5.34), alcohol consumption (aOR= 1.7, 95% CI=1.16-2.49), consuming a non-vegetarian diet (aOR=1.38, 95% CI=1.08-1.76), not drinking milk (aOR=1.7, 95% CI= 1.29-2.24), not using a toothbrush for cleaning of teeth (aOR=2.98, 95% CI =1.71-5.21) and not cleaning teeth at least once a day (aOR=2.13, 95% CI=1.58-2.87).

    CONCLUSION: Risk factors for periodontitis in a rural Indian population were identified. Further studies should validate these findings and appropriate recommendations should be developed to decrease the prevalence and burden of periodontitis in this population.

  2. Ramachandran V, Ismail P, Stanslas J, Shamsudin N
    PMID: 19243623 DOI: 10.1186/1475-2840-8-11
    The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.
  3. Ramachandran V, Marimuthu RR, Chinnambedu RS
    Med J Malaysia, 2020 05;75(3):314-315.
    PMID: 32467555
    No abstract provided.
  4. Nemati R, Lu J, Ramachandran V, Etemad A, Heidari M, Yahya MJ, et al.
    Genet. Mol. Res., 2016 Jun 20;15(2).
    PMID: 27323204 DOI: 10.4238/gmr.15026241
    The aim of this study was to determine whether C34T, a common polymorphism of the adenosine monophosphate deaminase 1 gene (AMPD1), is associated with essential hypertension (EH). We hypothesize that C34T is associated with the development of EH. A case-control design was used for this study. The DNA was extracted using a commercial kit from the whole blood of 200 patients with hypertension and 200 subjects without hypertension from selected Malaysian ethnicities (Malays, Chinese, and Indians). Polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP) and agarose gel electrophoresis were used for genotyping. The C34T gene polymorphism of AMPD1 was significantly associated with EH in the Malaysian subjects (P < 0.0001). The genotype frequencies of CC, CT, and TT were 6%, 79%, and 15%, respectively, among hypertensive subjects, while no TT genotypes were observed in the normotensive subjects. Further, the frequency of hypertension was higher among T allele carriers than C carriers (OD = 9.94; 95%CI = 6.851-14.434). There were significant differences in the systolic blood pressure, diastolic blood pressure, and pulse pressure (P ˂ 0.05) between the normotensive and hypertensive Malaysian subjects; we believe those difference were caused by the C34T polymorphism. For the first time in Malaysia, the current study provides evidence that a common polymorphism of the AMPD1 gene (C34T) is strongly associated with EH.
  5. Almeamar HA, Ramachandran V, Ismail P, Nadkarni P, Fawzi N
    Syst Biol Reprod Med, 2013 Apr;59(2):99-107.
    PMID: 23231020 DOI: 10.3109/19396368.2012.748851
    Complete deletions in the AZF (a, b, and c) sub-regions of the Y-chromosome have been shown to contribute to unexplained male infertility. However, the role of partial AZFc deletions in male infertility remains to be verified. Three types of partial AZFc deletions have been identified. They are gr/gr, b1/b3, and b2/b3 deletions. A recent meta-analysis showed that ethnic and geographical factors might contribute to the association of partial AZFc deletions with male infertility. This study analyzed the association of partial AZFc deletions in Malaysian infertile males. Fifty two oligozoospermic infertile males and 63 fertile controls were recruited to this study. Screening for partial AZFc deletions was done using the two sequence-tagged sites approach (SY1291 and SY1191) which were analyzed using both the conventional PCR gel-electrophoresis and the high resolution melt, HRM method. Gr/gr deletions were found in 11.53% of the cases and 9.52% of the controls (p = 0.725). A B2/b3 deletion was found in one of the cases (p = 0.269). No B1/b3 deletions were identified in this study. The results of HRM analysis were consistent with those obtained using the conventional PCR gel-electrophoresis method. The HRM analysis was highly repeatable (95% limit of agreement was -0.0879 to 0.0871 for SY1191 melting temperature readings). In conclusion, our study showed that partial AZFc deletions were not associated with male infertility in Malaysian subjects. HRM analysis was a reliable, repeatable, fast, cost-effective, and semi-automated method which can be used for screening of partial AZFc deletions.
  6. Khazaei S, Abdul Hamid R, Mohd Esa N, Ramachandran V, Aalam GT, Etemad A, et al.
    BMC Complement Altern Med, 2017 Feb 10;17(1):104.
    PMID: 28187719 DOI: 10.1186/s12906-017-1594-6
    BACKGROUND: Liver cancer is a high incidence and fatal disease, the fifth most frequent cancer worldwide that is usually diagnosed at an advanced stage. The number of deaths from liver cancer has not declined even following various therapies. Plant secondary metabolites and their semi-synthetic derivatives play a principal role in anti-cancer drug therapy, since they are effective in the treatment of specific characteristics while also reducing side effects. Allium atroviolaceum, a plant of the genus Allium has been used in folk medicine to protect against several diseases. However, cytotoxicity and the anti-proliferative effect of Allium atroviolaceum remain unclear. This work aims to investigate the anticancer properties of Allium atroviolaceum and the mechanism of action.

    METHODS: To evaluate the in vitro cytotoxicity of flower of Allium atroviolaceum, methanol extract at a dose range from 100 to 3.12 μg/ml was assessed against the HepG2 hepatocarcinoma cell line, and also on normal 3T3 cells, by monitoring proliferation using the MTT assay method. A microscopy study was undertaken to observe morphological changes of HepG2 cells after treatment and cell cycle arrest and apoptosis were studied using flow cytometry. The apoptosis mechanism of action was assessed by the level of caspase-3 activity and expression of apoptosis related genes, Bcl-2, Cdk1 and p53. The combination effect of the methanolic extract with doxorubicin was also investigated by determination of a combination index.

    RESULTS: The results demonstrated growth inhibition of cells in both dose- and time-dependent manners, while no cytotoxic effect on normal cell 3T3 was found. The results revealed the occurrence of apoptosis, illustrated by sub-G0 cell cycle arrest, the change in morphological feature and annexin-V and propidium iodide staining, which is correlated with Bcl-2 downregulation and caspase-3 activity, but p53-independent. In addition, a combination of Allium atroviolaceum and doxorubicin led to a significant synergistic effect.

    CONCLUSION: These findings suggest that Allium atroviolaceum flower extract has potential as a potent cytotoxic agent against HepG2 cell lines, as it has commendable anti-proliferative activities against human hepatocarcinoma and it can be considered as an effective adjuvant therapeutic agent after the clinical trials.

  7. Ibrahim SF, Pickering J, Ramachandran V, Roberts KJ
    Pharm Res, 2022 Dec;39(12):3063-3078.
    PMID: 35778633 DOI: 10.1007/s11095-022-03314-x
    PURPOSE: Development of a quantitative model and associated workflow for predicting the mechanical deformation properties (plastic deformation or cleavage fracture) of organic single crystals from their crystallographic structures using molecular and crystallographic modelling.

    METHODS: Intermolecular synthons, hydrogen bonding, crystal morphology and surface chemistry are modelled using empirical force fields with the data integrated into the analysis of lattice deformation as computed using a statistical approach.

    RESULTS: The approach developed comprises three main components. Firstly, the identification of the likely direction of deformation based on lattice unit cell geometry; secondly, the identification of likely lattice planes for deformation through the calculation of the strength and stereochemistry of interplanar intermolecular interactions, surface plane rugosity and surface energy; thirdly, identification of potential crystal planes for cleavage fracture by assessing intermolecular bonding anisotropy. Pentaerythritol is predicted to fracture by brittle cleavage on the {001} lattice planes by strong in-plane hydrogen-bond interactions in the <110>, whereas pentaerythritol tetranitrate is predicted to deform by plastic deformation through the slip system {110} , with both predictions being in excellent agreement with known experimental data.

    CONCLUSION: A crystallographic framework and associated workflow for predicting the mechanical deformation of molecular crystals is developed through quantitative assessment of lattice energetics, crystal surface chemistry and crystal defects. The potential for the de novo prediction of the mechanical deformation of pharmaceutical materials using this approach is highlighted for its potential importance in the design of formulated drug products process as needed for manufacture by direct compression.

  8. Ramachandran V, Ismail P, Stanslas J, Shamsudin N, Moin S, Mohd Jas R
    PMID: 19126661 DOI: 10.1177/1470320308097499
    The deletion (D) allele of the angiotensin-converting enzyme (ACE) gene has been studied in various populations in relation to hypertension (HTN) and type 2 diabetes mellitus (T2DM) with contradictory results. This study sought to determine the association of insertion (I)/D polymorphism of the ACE gene in hypertensive and T2DM subjects in a Malaysian population.
  9. Ching SM, Yee A, Ramachandran V, Sazlly Lim SM, Wan Sulaiman WA, Foo YL, et al.
    PLoS One, 2015;10(10):e0139337.
    PMID: 26431511 DOI: 10.1371/journal.pone.0139337
    This study was initiated to determine the psychometric properties of the Smart Phone Addiction Scale (SAS) by translating and validating this scale into the Malay language (SAS-M), which is the main language spoken in Malaysia. This study can distinguish smart phone and internet addiction among multi-ethnic Malaysian medical students. In addition, the reliability and validity of the SAS was also demonstrated.
  10. Haghvirdizadeh P, Ramachandran V, Etemad A, Heidari F, Ghodsian N, Bin Ismail N, et al.
    J Diabetes Res, 2015;2015:289846.
    PMID: 26451383 DOI: 10.1155/2015/289846
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a complex polygenic disorder characterized by impaired insulin resistance, insulin secretion, and dysregulation of lipid and protein metabolism with environmental and genetic factors. ATP-binding cassette transporter A1 (ABCA1) gene polymorphisms are reported as the one of the genetic risk factors for T2DM in various populations with conflicting results. This study was conducted based on PCR-HRM to determine the frequency of ABCA1 gene by rs2230806 (R219K), rs1800977 (C69T), and rs9282541 (R230C) polymorphisms Malaysian subjects.

    METHODS: A total of 164 T2DM and 165 controls were recruited and their genotypes for ABCA1 gene polymorphisms were determined based on the real time high resolution melting analysis.

    RESULTS: There was a significant difference between the subjects in terms of age, BMI, FPG, HbA1c, HDL, LDL, and TG (P < 0.05). There was a significant association between HOM of R219K (P = 0.005), among Malaysian subjects; moreover, allele frequency revealed the significant difference in A allele of R219K (P = 0.003). But, there was no significant difference in genotypic and allelic frequencies of C69T and R230C polymorphism.

    CONCLUSION: R219K polymorphism of ABCA1 gene can be considered as a genetic risk factor for T2DM subjects among Malaysians.

  11. Janahiraman S, Aziz MN, Hoo FK, P'ng HS, Boo YL, Ramachandran V, et al.
    Pak J Med Sci, 2015 Nov-Dec;31(6):1383-8.
    PMID: 26870101 DOI: 10.12669/pjms.316.8445
    Antimicrobial resistance is a major health problem worldwide in hospitals. The main contributing factors are exposures to broad-spectrum antimicrobials and cross-infections. Understanding the extent and type of antimicrobial use in tertiary care hospitals will aid in developing national antimicrobial stewardship priorities.
  12. Ghodsian N, Akhlaghi M, Ramachandran V, Heidari F, Haghvirdizadeh P, Eshkoor SA, et al.
    Genet. Mol. Res., 2015 Dec 29;14(4):18974-9.
    PMID: 26782547 DOI: 10.4238/2015.December.29.4
    This study aims to investigate the effects of tumor necrosis factor alpha (TNF-α) G308A gene polymorphism on essential hypertension (EHT) with or without type 2 diabetes mellitus (T2DM). The project was conducted on buccal epithelial and blood cells for case and control patients, respectively. Epithelial cells were obtained from the inner part of the cheeks. Techniques including DNA extraction, polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLP) were utilized to assess biomarkers of DNA damage. Our results demonstrated significant differences between wild and mutated genotypes among EHT patients without T2DM. We also found a significant association between wild and mutated allele frequencies in EHT patients (P < 0.05). Clinical characteristics between the groups (EHT with or without T2DM and controls) showed statistically significant association (P < 0.05). Overall, we show that G308A polymorphism of the TNF-αgene may be a significant genetic risk factor for EHT without T2DM patients in Malaysia.
  13. Rati Selvaraju T, Khaza'ai H, Vidyadaran S, Sokhini Abd Mutalib M, Ramachandran V, Hamdan Y
    Int J Vitam Nutr Res, 2014;84(3-4):140-51.
    PMID: 26098478 DOI: 10.1024/0300-9831/a000201
    Glutamate is the major mediator of excitatory signals in the mammalian central nervous system. Extreme amounts of glutamate in the extracellular spaces can lead to numerous neurodegenerative diseases. We aimed to clarify the potential of the following vitamin E isomers, tocotrienol-rich fraction (TRF) and α-tocopherol (α-TCP), as potent neuroprotective agents against glutamate-induced injury in neuronal SK-N-SH cells. Cells were treated before and after glutamate injury (pre- and post-treatment, respectively) with 100-300 ng/ml TRF/α-TCP. Exposure to 120 mM glutamate significantly reduced cell viability to 76% and 79% in the pre- and post-treatment studies, respectively; however, pre- and post-treatment with TRF/α-TCP attenuated the cytotoxic effect of glutamate. Compared to the positive control (glutamate-injured cells not treated with TRF/α-TCP), pre-treatment with 100, 200, and 300 ng/ml TRF significantly improved cell viability following glutamate injury to 95.2%, 95.0%, and 95.6%, respectively (p<0.05).The isomers not only conferred neuroprotection by enhancing mitochondrial activity and depleting free radical production, but also increased cell viability and recovery upon glutamate insult. Our results suggest that vitamin E has potent antioxidant potential for protecting against glutamate injury and recovering glutamate-injured neuronal cells. Our findings also indicate that both TRF and α-TCP could play key roles as anti-apoptotic agents with neuroprotective properties.
  14. Chinnambedu RS, Marimuthu RR, Sunil SS, Amrose P, Ramachandran V, Pachamuthu B
    J Infect Public Health, 2020 Jan;13(1):75-79.
    PMID: 31402312 DOI: 10.1016/j.jiph.2019.06.015
    PURPOSE: Emergence of multidrug-resistant and methicillin-resistant Staphylococcus aureus (MRSA) infections in HIV patients limit the treatment options and challenge the clinical management of infections. The periodic monitoring of S. aureus infections and its drug resistance profile in HIV patients are of paramount importance in clinical management.

    MATERIALS AND METHODS: A total of 7204 clinical specimens from HIV patients from 2012 to 2017 were processed for the isolation of S. aureus strains using conventional culture techniques and cultures were identified using standard biochemical test. Antibiotic susceptibility of S. aureus strains was tested by Kirby-Bauer disk diffusion method.

    RESULTS: A total of 380 (5.3%) S. aureus strains were isolated from HIV patients in the study period. High percentage of S. aureus strains were isolates from urine (69.5%) specimen and 58.4% of S. aureus infections were noted among hospitalized patients. Antibiotic susceptibility profile reveals S. aureus was highly resistant to penicillin (95.2%) followed by cephalexin (84.6%). Methicillin resistance was highly observed in the year 2017 (86%) and the rate of MRSA steadily increasing from 51.8% in 2012 to 86% in 2017. Significant increase of S. aureus infections (35%; p<0.001) and MRSA (76%; p=0.0007) were observed in the year 2016.

    CONCLUSIONS: This study reports the increasing trends of S. aureus infections and MRSA among HIV patients from Southern India. Multidrug-resistance profile of S. aureus could complicate the selection of proper antibiotic regimens and time cure of HIV patients.

  15. Lim SY, Chan YM, Ramachandran V, Shariff ZM, Chin YS, Arumugam M
    PMID: 33478001 DOI: 10.3390/ijerph18020827
    BACKGROUND: Evidence is growing that a high-acid diet might accelerate the rate of bone loss, and gene polymorphisms such as Interleukin 6 (IL6) -174G/C and -572G/C are related to bone deterioration. However, no study of the interaction between diet and IL6 polymorphisms has been conducted among Asians. Thus, the objective of this study was to determine whether IL6 gene polymorphisms modified the association between dietary acidity and the rate of bone resorption.

    METHODS: This cross-sectional study recruited 203 postmenopausal women (age ranged from 51 to 85 years old) in community settings. The dietary intakes of the participants were assessed using a validated interviewer-administered semi-quantitative food frequency questionnaire (FFQ), while dietary acid load (DAL) was estimated using net endogenous acid production (NEAP). Agena® MassARRAY genotyping analysis and serum collagen type 1 cross-linked C-telopeptide (CTX1) were used to identify the IL6 genotype and as a bone resorption marker, respectively. The interactions between diet and single-nucleotide polymorphisms (SNPs) were assessed using linear regressions.

    RESULTS: A total of 203 healthy postmenopausal women aged between 51 and 85 years participated in this study. The mean BMI of the participants was 24.3 kg/m2. In IL6 -174 G/C, all the participants carried the GG genotype, while the C allele was absent. Approximately 40% of the participants had a high dietary acid load. Dietary acid load (B = 0.15, p = 0.031) and the IL6 -572 CC genotype group (B = 0.14, p = 0.044) were positively associated with a higher bone resorption. However, there was no moderating effect of the IL6 genetic polymorphism on the relationship between and acid ash diet and bone resorption markers among the postmenopausal women (p = 0.79).

    CONCLUSION: High consumption of an acid ash diet and the IL6 -572 C allele seem to attribute to high bone resorption among postmenopausal women. However, our finding does not support the interaction effect of dietary acidity and IL6 (-174G/C and -572G/C) polymorphisms on the rate of bone resorption. Taken together, these results have given scientific research other candidate genes to focus on which may interact with DAL on bone resorption, to enhance planning for preventing or delaying the onset of osteoporosis among postmenopausal women.

  16. Lim SY, Chan YM, Ramachandran V, Shariff ZM, Chin YS, Arumugam M
    Nutrients, 2021 Jun 23;13(7).
    PMID: 34201855 DOI: 10.3390/nu13072161
    The objective of this study was to explore the effects of dietary acid load (DAL) and IGF1 and IL6 gene polymorphisms and their potential diet-gene interactions on metabolic traits. A total of 211 community-dwelling postmenopausal women were recruited. DAL was estimated using potential renal acid load (PRAL). Blood was drawn for biochemical parameters and DNA was extracted and Agena® MassARRAY was used for genotyping analysis to identify the signalling of IGF1 (rs35767 and rs7136446) and IL6 (rs1800796) polymorphisms. Interactions between diet and genetic polymorphisms were assessed using regression analysis. The result showed that DAL was positively associated with fasting blood glucose (FBG) (β = 0.147, p < 0.05) and there was significant interaction effect between DAL and IL6 with systolic blood pressure (SBP) (β = 0.19, p = 0.041). In conclusion, these findings did not support the interaction effects between DAL and IGF1 and IL6 single nucleotide polymorphisms (rs35767, rs7136446, and rs1800796) on metabolic traits, except for SBP. Besides, higher DAL was associated with higher FBG, allowing us to postulate that high DAL is a potential risk factor for diabetes.
  17. Lee TY, Lai MI, Ramachandran V, Tan JA, Teh LK, Othman R, et al.
    Int J Lab Hematol, 2016 Aug;38(4):435-43.
    PMID: 27349818 DOI: 10.1111/ijlh.12520
    INTRODUCTION: Alpha thalassaemia is a highly prevalent disease globally and is a well-known public health problem in Malaysia. The deletional forms of the mutation are the most common forms found in alpha thalassaemia. The three most common deletional alpha thalassaemia found in this region include --(SEA) deletion, -α(3.7) rightward and -α(4.2) leftward deletions. The prevalence rate of triplication alpha cases such as ααα(anti3.7) and ααα(anti4.2) is not known in Malaysia although it plays a role in exacerbating the clinical phenotypes in beta thalassaemia carriers. Recently, there have been more reported cases of rare alpha thalassaemia mutations due to the advancement of molecular techniques involved in thalassaemia detections. Therefore, it is essential to develop a new method which allows the detection of different alpha thalassaemia mutations including the rare ones simultaneously and accurately.

    METHODS: The purpose of this study was to design an assay for the detection of triplications, common and rare deletional alpha thalassaemia using droplet digital PCR (ddPCR).

    RESULTS: This is a quantitative detection method to measure the changes of copy number which can detect deletions, duplications and triplications of the alpha globin gene simultaneously.

    CONCLUSION: In conclusion, ddPCR is an alternative method for rapid detection of alpha thalassaemia variants in Malaysia.

  18. Khazaei S, Ramachandran V, Abdul Hamid R, Mohd Esa N, Etemad A, Moradipoor S, et al.
    Biomed Pharmacother, 2017 May;89:1216-1226.
    PMID: 28320088 DOI: 10.1016/j.biopha.2017.02.082
    Cervical cancer accounts for the second most frequent cancer and also third leading cause of cancer mortality (15%) among women worldwide. The major problems of chemotherapeutic treatment in cervical cancer are non-specific cytotoxicity and drug resistance. Plant-derived products, known as natural therapies, have been used for thousands of years in cancer treatment with a very low number of side effects. Allium atroviolaceum is a species in the genus Allium and Liliaceae family, which could prove to have beneficial effects on cancer treatment, although there is a lack of corresponding attention. The methanolic extract from the A.atroviolaceum flower displayed marked anticancer activity on HeLa human cervix carcinoma cells with much lower cytotoxic effects on normal cells (3T3). The A.atroviolaceum extract induced apoptosis, confirmed by cell cycle arrest at the sub-G0 (apoptosis) phase, characteristic morphological changes, evident DNA fragmentation, observed by fluorescent microscope, and early and late apoptosis detection by Annexin V. Furthermore, down-regulation of Bcl-2 and activation of caspase-9 and -3 strongly indicated that the mitochondrial pathway was involved in the apoptosis signal pathway. Moreover, combination of A.atroviolaceum extract with doxorubicin revealed a significant reduction of IC50and led to a synergistic effect. In summary, A.atroviolaceum displayed a significant anti-tumour effect through apoptosis induction in HeLa cells, suggesting that the A.atroviolaceum flower might have therapeutic potential against cervix carcinoma.
  19. Khazaei S, Esa NM, Ramachandran V, Hamid RA, Pandurangan AK, Etemad A, et al.
    Front Pharmacol, 2017;8:5.
    PMID: 28197098 DOI: 10.3389/fphar.2017.00005
    Natural products are considered potent sources for novel drug discovery and development. The multiple therapeutic effects of natural compounds in traditional medicine motivate us to evaluate the cytotoxic activity of bulb of Allium atroviolaceum in MCF7 and MDA-MB-231, HeLa and HepG2 cell lines. The bulb methanol extract of A. atroviolaceum was found to be an active cell proliferation inhibitor at the time and dose dependent manner. Determination of DNA content by flow cytometry demonstrated S and G2/M phase arrest of MCF-7 cell, correlated to Cdk1 downregulation, S phase arrest in MDA-MB-231 which is p53 and Cdk1-dependent, sub-G0 cell cycle arrest in HeLa aligned with Cdk1 downregulation, G0/G1, S, G2/M phase arrest in HepG2 which is p53-dependent. Apoptosis as the mechanism of cell death was confirmed by morphology study, caspases activity assay, as well as apoptosis related gene expression, Bcl-2. Caspase-8, -9, and -3 activity with downregulation of Bcl-2 illustrated occurrence of both intrinsic and extrinsic pathways in MCF7, while caspase-3 and -8 activity revealed extrinsic pathway of apoptosis, although Bcl-2 downregulated. In HeLa cells, the activity of caspase-9 and -3 and downregulation of Bcl-2 shows intrinsic pathway or mitochondrial pathway, whereas HepG2 shows caspase independent apoptosis. Further, the combination of the extract with tamoxifen against MCF7 and MDA-MB-231 and combination with doxorubicin against HeLa and HeG2 demonstrated synergistic effect in most concentrations, suggests that the bulb of A. atroviolaceum may be useful for the treatment of cancer lonely or in combination with other drugs.
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