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Anti-proliferative and anti-invasive properties of a purified fraction from Streptomyces sp. H7372

Yip WK, Cheenpracha S, Chang LC, Ho CC, Seow HF

Int J Oncol, 2010 Nov;37(5):1229-41.
PMID: 20878070

Secondary metabolites from actinomycetes especially the genus Streptomyces may be one of the most important sources for novel anticancer agents. A purified fraction from a novel actinomycete strain, Streptomyces sp. H7372, was elucidated in breast cancer cells. We have isolated three purified fractions from a novel strain, Streptomyces sp. H7372. One of the fractions, designated as 31-2, exhibited the strongest growth-inhibitory effect and thereby was selected for further studies. 31-2 exerted a growth-inhibitory effect on a panel of 15 human cancer and 2 non-malignant cell lines. In MCF-7 and MDA-MB-231 breast cancer cells, 31-2 induced a cytostatic (anti-proliferative) effect without causing cytotoxicity (cell death). Our data suggest that the cytostasis resulted from cell cycle arrest at the G1 phase in MCF-7 cells and at the S phase in MDA-MB-231 cells. Western blot analysis demonstrated a modulation of phosphorylation of the Rb and CDC2 proteins and of CDK4, cyclin D1 and cyclin D3 in the 31-2-treated breast cancer cell lines. The protein levels of CDK2, CDK6, and PCNA were not affected by 31-2 treatment. 31-2 also exhibited an anti-invasive effect in MDA-MB-231 cells. However, this effect is not attributed to the modulation of proteolytic activity in MDA-MB-231 cells as the enzymatic degradation of type IV collagen was not affected by 31-2. The 31-2 is a potent cytostatic and anti-invasive agent and modulates the cell cycle pathway. Together, these results will have important implications in searching for novel approaches to treat cancer.

Matched MeSH terms: Apoptosis/drug effects
Apoptosis in Acanthamoeba castellanii belonging to the T4 genotype

Baig AM, Lalani S, Khan NA

J Basic Microbiol, 2017 Jul;57(7):574-579.
PMID: 28466971 DOI: 10.1002/jobm.201700025

Here we describe features of apoptosis in unicellular Acanthamoeba castellanii belonging to the T4 genotype. When exposed to apoptosis-inducing compounds such as doxorubicin, A. castellanii trophozoites exhibited cell shrinkage and membrane blebbing as observed microscopically, DNA fragmentation using agarose gel electrophoresis, and phosphatidylserine (PS) externalization using annexin V immunostaining. Overall, these findings suggest the existence of apoptosis in A. castellanii possibly mediated by intrinsic apoptotic cascade. Further research in this field could provide avenues to selectively induce apoptosis in A. castellanii by triggering intrinsic apoptotic cascade.

Matched MeSH terms: Apoptosis*
Modulation of the benzene metabolite hydroquinone induced toxicity: evidence for an important role of fau

Inayat-Hussain SH, Ibrahim HA, Siew EL, Rajab NF, Chan KM, G T Williams, et al.

Chem Biol Interact, 2010 Mar 19;184(1-2):310-2.
PMID: 20025857 DOI: 10.1016/j.cbi.2009.12.009
Matched MeSH terms: Apoptosis/drug effects
Goniothalamin induces apoptosis in vascular smooth muscle cells

Chan KM, Rajab NF, Ishak MH, Ali AM, Yusoff K, Din LB, et al.

Chem Biol Interact, 2006 Feb 1;159(2):129-40.
PMID: 16297902

Restenosis represents a major impediment to the success of coronary angioplasty. Abnormal proliferation of vascular smooth muscle cells (VSMCs) has been shown to be an important process in the pathogenesis of restenosis. A number of agents, particularly rapamycin and paclitaxel, have been shown to impact on this process. This study was carried out to determine the mechanisms of cytotoxicity of goniothalamin (GN) on VSMCs. Results from MTT cytotoxicity assay showed that the IC(50) for GN was 4.4 microg/ml (22 microM), which was lower compared to the clinically used rapamycin (IC(50) of 25 microg/ml [27.346 microM]). This was achieved primarily via apoptosis where up to 25.83 +/- 0.44% of apoptotic cells were detected after 72 h treatment with GN. In addition, GN demonstrated similar effects as rapamycin in inhibiting VSMCs proliferation using bromodeoxyuridine (BrdU) cell proliferation assay after 72 h treatment at IC(50) concentration (p > 0.05). In order to understand the mechanisms of GN, DNA damage detection using comet assay was determined at 2h post-treatment with GN. Our results showed that there was a concentration-dependent increase in DNA damage in VSMCs prior to cytotoxicity. Moreover, GN effects were comparable to rapamycin. In conclusion, our data show that GN initially induces DNA damage which subsequently leads to cytotoxicity primarily via apoptosis in VSMCs.

Matched MeSH terms: Apoptosis/drug effects*
Effect of kidney ischemia/reperfusion injury on proliferation, apoptosis, and cellular senescence in acute kidney injury in mice

Sari FT, Sari FT, Sari FT, Arfian N, Sari DCR

Med J Malaysia, 2020 05;75(Suppl 1):20-23.
PMID: 32471965

INTRODUCTION: Kidney ischemia/reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI). Kidney IRI demonstrated apoptosis of epithelial cells in acute phase followed by proliferation of interstitial cells in chronic episode, and cellular senescence may contribute to development of AKI, however, its occurrence within acute or chronic episodes is still not completely understood.
METHODS: Kidney IRI was performed with bilateral pediculus clamping in Swiss Background mice (3 months, 30-40g). Mice were euthanised on day one (I/R1, n=6), day eight (I/R8, n=6), and day twelve (I/R12, n=6) to exam acute and chronic episodes. Sham operation procedure was performed in the control. Tubular injury was assessed based on periodic acid- Schift (PAS) staining. Reverse transcriptase PCR (RT-PCR) was done to quantify mRNA expression of Bax, Bcl-2, and p16. Immunohistostaining (IHC) was performed to examine localisation of apoptosis (p53) and proliferation (Bcl-2).
RESULTS: RT-PCR analysis showed upregulation of mRNA expression of Bcl-2, Bax, and p16 (p<0.05). The data showed that ischemia/reperfusion induces upregulation of Bax (p=0.20), Bcl-2 (p=0.45), p16 (p=0.18). Apoptosis and proliferation occurred in the epithelial cells in acute episodes, but occurred in interstitial areas in chronic episodes.
CONCLUSIONS: Ischemia/reperfusion injury induces upregulation proliferation, apoptosis, and cellular senescence in acute kidney injury. Apoptosis reached its peak on day 1, proliferation on day 8, and cellular senescence on day 12.

Matched MeSH terms: Apoptosis*
4-chloro-1,2-phenylenediamine induces apoptosis in Mardin-Darby canine kidney cells via activation of caspases

Onn LC, Ching CS, Lian TY, Foon LV, Chew Hee N, Moi CS

Environ Toxicol, 2014 Jun;29(6):655-64.
PMID: 22778066 DOI: 10.1002/tox.21792

4-Chloro-1,2-phenylenediamine (4-Cl-o-PD) is a halogenated aromatic diamine that was used as a precursor for manufacturing permanent hair dyes. Despite its well-documented mutagenic and carcinogenic effects in a number of in vitro and in vivo models, its cytotoxicity and mode of action have not received similar attention. Here, we investigated the effect of 4-Cl-o-PD on Mardin-Darby canine kidney cells. It induced apoptosis and the evidence suggests its initiation by reactive oxygen species (ROS). The results of various assays used show a dose-dependent (i) decrease in cell viability, (ii) increase in cells at sub-G1 phase and the G0/G1 phase arrested in cell cycle, (iii) increase in intracellular ROS accompanied by depletion of glutathione, and (iv) that apoptotic cell death probably involves activation of both intrinsic and extrinsic pathways.

Matched MeSH terms: Apoptosis/drug effects*
Fulltext Detrimental Effects of UVB on Retinal Pigment Epithelial Cells and Its Role in Age-Related Macular Degeneration

Mahendra CK, Tan LTH, Pusparajah P, Htar TT, Chuah LH, Lee VS, et al.

Oxid Med Cell Longev, 2020;2020:1904178.
PMID: 32855763 DOI: 10.1155/2020/1904178

Retinal pigment epithelial (RPE) cells are an essential part of the human eye because they not only mediate and control the transfer of fluids and solutes but also protect the retina against photooxidative damage and renew photoreceptor cells through phagocytosis. However, their function necessitates cumulative exposure to the sun resulting in UV damage, which may lead to the development of age-related macular degeneration (AMD). Several studies have shown that UVB induces direct DNA damage and oxidative stress in RPE cells by increasing ROS and dysregulating endogenous antioxidants. Activation of different signaling pathways connected to inflammation, cell cycle arrest, and intrinsic apoptosis was reported as well. Besides that, essential functions like phagocytosis, osmoregulation, and water permeability of RPE cells were also affected. Although the melanin within RPE cells can act as a photoprotectant, this photoprotection decreases with age. Nevertheless, the changes in lens epithelium-derived growth factor (LEDGF) and autophagic activity or application of bioactive compounds from natural products can reverse the detrimental effect of UVB. Additionally, in vivo studies on the whole retina demonstrated that UVB irradiation induces gene and protein level dysregulation, indicating cellular stress and aberrations in the chromosome level. Morphological changes like retinal depigmentation and drusen formation were noted as well which is similar to the etiology of AMD, suggesting the connection of UVB damage with AMD. Therefore, future studies, which include mechanism studies via in vitro or in vivo and other potential bioactive compounds, should be pursued for a better understanding of the involvement of UVB in AMD.

Matched MeSH terms: Apoptosis/radiation effects
Pinocembrin enriched fraction of Elytranthe parasitica (L.) Danser induces apoptosis in HCT 116 colorectal cancer cells

Kumar N, Biswas S, Hosur Shrungeswara A, Basu Mallik S, Hipolith Viji M, Elizabeth Mathew J, et al.

J Infect Chemother, 2017 Jun;23(6):354-359.
PMID: 28385566 DOI: 10.1016/j.jiac.2017.02.009

BACKGROUND: Colorectal cancer (CRC) is a highly predominant malignancy affecting millions worldwide. Plants belonging to Loranthaceae family have remarkable chemopreventive properties.
OBJECTIVE: The goal of the present study was to assess the antiproliferative and apoptosis-inducing effects of stem parts of Elytranthe parasitica (L.) Danser (EP) on colorectal cancer and identify the bioactive phytochemicals.
MATERIAL AND METHODS: EP methanol extract (EP.M) and its subsequent fractions were screened for antiproliferative activity in human colorectal carcinoma HCT 116 cell line. Phytocomposition of the bioactive fraction was analyzed by GC-MS. Further, apoptotic induction and cell cycle arrest was assessed in the most bioactive fractions.
RESULTS: EP.DEE (Diethyl Ether) fraction and a subsequent fraction derived by column chromatography, Fraction 3A (FR 3A) significantly inhibited the proliferation of HCT 116 cells (P

Matched MeSH terms: Apoptosis/drug effects*
Fulltext Anticancer activity of Momordica cochinchinensis (red gac) aril and the impact of varietal diversity

Wimalasiri D, Dekiwadia C, Fong SY, Piva TJ, Huynh T

BMC Complement Med Ther, 2020 Nov 25;20(1):365.
PMID: 33238969 DOI: 10.1186/s12906-020-03122-z

BACKGROUND: Momordica cochinchinensis (Cucurbitaceae) is a nutritionally and medicinally important fruit restricted to South East Asia with diverse morphological and genetic variations but there is limited information on its medicinal potential.
METHODS: M. cochinchinensis aril from 44 different samples in Australia, Thailand and Vietnam were extracted using different solvents and tested for its anticancer potential. Anticancer activity of M. cochinchinensis aril on breast cancer (MCF7 and BT474) and melanoma (MM418C1 and D24) cells were compared to control fibroblasts (NHDF). The cytotoxicity of the cells following treatment with the aril extract was determined using CCK-8 assay. Biochemical and morphological changes were analysed using flow cytometry, confocal and transmission electron microscopy to determine the mechanism of cell death.
RESULTS: The water extract from the aril of M. cochinchinensis elicited significantly higher cytotoxicity towards breast cancer and melanoma cells than the HAE extract. The IC50 concentration for the crude water extract ranged from 0.49 to 0.73 mg/mL and induced both apoptotic and necrotic cell death in a dose- and time-dependant manner with typical biochemical and morphological characteristics. The greatest cytotoxicity was observed from Northern Vietnam samples which caused 70 and 50% melanoma and breast cancer cell death, respectively.
CONCLUSIONS: The water extract of M. cochinchinensis aril caused significant apoptosis and necrosis of breast cancer and melanoma cells, with varieties from Northern Vietnam possessing superior activity. This highlights the potential of this fruit in the development of novel anticancer agents against such tumours, with specific regions on where to collect the best variety and extraction solvent for optimum activity.

Matched MeSH terms: Apoptosis/drug effects
Vernodalin induces apoptosis through the activation of ROS/JNK pathway in human colon cancer cells

Mohebali N, Pandurangan AK, Mustafa MR, Anandasadagopan SK, Alagumuthu T

J Biochem Mol Toxicol, 2020 Dec;34(12):e22587.
PMID: 32726518 DOI: 10.1002/jbt.22587

Colorectal cancer is one of the most leading death-causing cancers in the world. Vernodalin, a cytotoxic sesquiterpene, has been reported to possess anticancer properties against human breast cancer cells. We aimed to examine the anticancer mechanism of vernodalin on human colon cancer cells. Vernodalin was used on human colon cancer cells, HT-29 and HCT116. The cytotoxicity of vernodalin on human colon cancer cells was determined through in vitro 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyl-tetrazolium bromide assay. Small interfering RNA was used to analyze the cascade activation of mitogen-activated protein kinase (MAPK) pathway, c-Jun N-terminal kinase (JNK) in HT-29, and HCT116 cells against vernodalin treatment. The protein expressions of caspase 3, Bcl-2, and Bax were examined through Western blot analysis. Immunoblot analysis on the JNK, ERK, and p38 MAPK pathways showed increased activation due to vernodalin treatment. It was proven from the JNK and p38 inhibition test that both pathways are significantly activated by vernodalin to induce apoptosis. Our results, collectively, showed the apoptosis-induced anticancer mechanism of vernodalin on human colon cancer cells that was mediated through the activation of JNK pathway and apoptotic regulator proteins. These results suggest that vernodalin could be developed as a potent chemotherapeutic agent for human colorectal cancer treatment.

Matched MeSH terms: Apoptosis/drug effects*
Fulltext Comparison of cytotoxicity between extracts of Clinacanthus nutans (Burm. f.) Lindau leaves from different locations and the induction of apoptosis by the crude methanol leaf extract in D24 human melanoma cells

Fong SY, Piva T, Dekiwadia C, Urban S, Huynh T

BMC Complement Altern Med, 2016 Sep 20;16:368.
PMID: 27646974 DOI: 10.1186/s12906-016-1348-x

Clinacanthus nutans (Burm. f.) Lindau leaves are widely used by cancer patients and the leaf extracts possess cytotoxic and antiproliferative effects on several human cancer cell lines. However, the effect of C. nutans leaf extract on human melanoma, which is the least common but most fatal form of skin cancer and one of the most common cancers diagnosed in both sexes worldwide, is unknown. There is also limited information on whether the bioactivity of extracts differs between C. nutans leaves grown in different geographical locations with varying environmental conditions.

Matched MeSH terms: Apoptosis/drug effects*
Identification of informative genes and pathways using an improved penalized support vector machine with a weighting scheme

Chan WH, Mohamad MS, Deris S, Zaki N, Kasim S, Omatu S, et al.

Comput Biol Med, 2016 10 01;77:102-15.
PMID: 27522238 DOI: 10.1016/j.compbiomed.2016.08.004

Incorporation of pathway knowledge into microarray analysis has brought better biological interpretation of the analysis outcome. However, most pathway data are manually curated without specific biological context. Non-informative genes could be included when the pathway data is used for analysis of context specific data like cancer microarray data. Therefore, efficient identification of informative genes is inevitable. Embedded methods like penalized classifiers have been used for microarray analysis due to their embedded gene selection. This paper proposes an improved penalized support vector machine with absolute t-test weighting scheme to identify informative genes and pathways. Experiments are done on four microarray data sets. The results are compared with previous methods using 10-fold cross validation in terms of accuracy, sensitivity, specificity and F-score. Our method shows consistent improvement over the previous methods and biological validation has been done to elucidate the relation of the selected genes and pathway with the phenotype under study.

Matched MeSH terms: Apoptosis/genetics
Possible Anticancer Mechanisms of Some Costus speciosus Active Ingredients Concerning Drug Discovery

El-Far AH, Badria FA, Shaheen HM

Curr Drug Discov Technol, 2016;13(3):123-143.
PMID: 27515456

Costus speciosus is native to South East Asia, especially found in India, Srilanka, Indonesia and Malaysia. C. speciosus have numerous therapeutic potentials against a wide variety of complains. The therapeutic properties of C. speciosus are attributed to the presence of various ingredients such as alkaloids, flavonoids, glycosides, phenols, saponins, sterols and sesquiterpenes. This review presented the past, present, and the future status of C. speciosus active ingredients to propose a future use as a potential anticancer agent. All possible up-regulation of cellular apoptotic molecules as p53, p21, p27, caspases, reactive oxygen species (ROS) generation and others attribute to the anticancer activity of C. speciosus along the down-regulation of anti-apoptotic agents such as Akt, Bcl2, NFKB, STAT3, JAK, MMPs, actin, surviving and vimentin. Eventually, we recommend further investigation of different C. speciosus extracts, using some active ingredients and evaluate the anticancer effect of these chemicals against different cancers.

Matched MeSH terms: Apoptosis/drug effects
Fulltext Ginger Extract (Zingiber officinale Roscoe) Triggers Apoptosis in Hepatocarcinogenesis Induced Rats

Yasmin Anum, M.Y., Shahriza, Z.A., Looi, ML, Shafina Hanim, M.H., Harlianshah, H., Noor Aini, A.H., et al.

Medicine & Health, 2008;3(2):263-274.
MyJurnal

Ginger extract has been reported previously by our group to exhibit anticancer and an-tioxidant effects by reducing tumour burden and lipid peroxidation respectively in he-patocarcinogenesis induced rats. The current study examined the expression of pro-apoptotic protein caspase-8 and anti-apoptotic protein Bcl-2 in hepatocarcinogenesis treated rats. Thirty normal male Wistar rats were divided into 5 groups based on the diet given: i) control (normal rat chow), ii) olive oil, iii) ginger extract (100mg/kg body weight), iv) choline deficient diet + ethionine, CDE (to induce liver cancer) and v) CDE+ ginger extract. Rats were killed at week 8, and liver tissues were excised for immuno-histochemical study to identify pro-apoptotic and anti-apoptotic proteins, caspase-8 and Bcl-2. The observation on H&E staining confirmed the CDE diet induced liver can-cer as indicated by the presence of numerous oval cells. Identification of Bcl-2 expres-sion showed that 91.6% (11/12) of the samples from the CDE group revealed positive staining while treatment with ginger extract however inhibited the expression with only 8.4% (1/12) samples showing positive staining for Bcl-2. As for caspase-8 protein, 41.7% (5/12) of the samples from CDE group showed positive staining, which in-creased to 100% (12/12) with ginger extract treatment. Our findings suggest that gin-ger extract has an anticancer effect by inducing apoptosis in liver cancer cells via up-regulation of the expression of pro-apoptotic protein, caspase-8 and down-regulation of the expression of anti-apoptotic protein Bcl-2.

Matched MeSH terms: Apoptosis; Apoptosis Regulatory Proteins
Fulltext Melicope ptelefolia leaf extracts exhibit antioxidant activity and exert anti-proliferative effect with apoptosis induction on four different cancer cell lines

Kabir MF, Mohd Ali J, Abolmaesoomi M, Hashim OH

BMC Complement Altern Med, 2017 May 05;17(1):252.
PMID: 28476158 DOI: 10.1186/s12906-017-1761-9

BACKGROUND: Melicope ptelefolia is a well-known herb in a number of Asian countries. It is often used as vegetable salad and traditional medicine to address various ailments. However, not many studies have been currently done to evaluate the medicinal benefits of M. ptelefolia (MP). The present study reports antioxidant, anti-proliferative, and apoptosis induction activities of MP leaf extracts.
METHOD: Young MP leaves were dried, powdered and extracted sequentially using hexane (HX), ethyl acetate (EA), methanol (MeOH) and water (W). Antioxidant activity was evaluated using ferric reducing antioxidant power (FRAP), 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-Diphenyl-2-picryl-hydrazyl (DPPH) radicals scavenging and cellular antioxidant activity (CAA) assays. Anti-proliferative activity was evaluated through cell viability assay, using the following four human cancer cell lines: breast (HCC1937, MDA-MB-231), colorectal (HCT116) and liver (HepG2). The anti-proliferative activity was further confirmed through cell cycle and apoptosis assays, including annexin-V/7-aminoactinomycin D staining and measurements of caspase enzymes activation and inhibition.
RESULT: Overall, MP-HX extract exhibited the highest antioxidant potential, with IC50 values of 267.73 ± 5.58 and 327.40 ± 3.80 μg/mL for ABTS and DPPH radical-scavenging assays, respectively. MP-HX demonstrated the highest CAA activity in Hs27 cells, with EC50 of 11.30 ± 0.68 μg/mL, while MP-EA showed EC50 value of 37.32 ± 0.68 μg/mL. MP-HX and MP-EA showed promising anti-proliferative activity towards the four cancer cell lines, with IC50 values that were mostly below 100 μg/mL. MP-HX showed the most notable anti-proliferative activity against MDA-MB-231 (IC50 = 57.81 ± 3.49 μg/mL) and HCT116 (IC50 = 58.04 ± 0.96 μg/mL) while MP-EA showed strongest anti-proliferative activity in HCT116 (IC50 = 64.69 ± 0.72 μg/mL). The anticancer potential of MP-HX and MP-EA were also demonstrated by their ability to induce caspase-dependent apoptotic cell death in all of the cancer cell lines tested. Cell cycle analysis suggested that both the MP-HX and MP-EA extracts were able to disrupt the cell cycle in most of the cancer cell lines.
CONCLUSIONS: MP-HX and MP-EA extracts demonstrated notable antioxidant, anti-proliferative, apoptosis induction and cancer cell cycle inhibition activities. These findings reflect the promising potentials of MP to be a source of novel phytochemical(s) with health promoting benefits that are also valuable for nutraceutical industry and cancer therapy.

Matched MeSH terms: Apoptosis/drug effects*
CD133: beyond a cancer stem cell biomarker

Barzegar Behrooz A, Syahir A, Ahmad S

J Drug Target, 2019 03;27(3):257-269.
PMID: 29911902 DOI: 10.1080/1061186X.2018.1479756

CD133 (prominin-1), a pentaspan membrane glycoprotein, is one of the most well-characterized biomarkers used for the isolation of cancer stem cells (CSCs). The presence of CSCs is one of the main causes of tumour reversal and resilience. Accumulating evidence has shown that CD133 might be responsible for CSCs tumourigenesis, metastasis and chemoresistance. It is now understood that CD133 interacts with the Wnt/β-catenin and PI3K-Akt signalling pathways. Moreover, CD133 can upregulate the expression of the FLICE-like inhibitory protein (FLIP) in CD133-positive cells, inhibiting apoptosis. In addition, CD133 can increase angiogenesis by activating the Wnt signalling pathway and increasing the expression of vascular endothelial growth factor-A (VEGF-A) and interleukin-8. Therefore, CD133 could be considered to be an 'Achilles' heel' for CSCs, because by inhibiting this protein, the signalling pathways that are involved in cell proliferation will also be inhibited. By understanding the molecular biology of CD133, we can not only isolate stem cells but can also utilise it as a therapeutic strategy. In this review, we summarise new insights into the fundamental cell biology of CD133 and discuss the involvement of CD133 in metastasis, metabolism, tumourigenesis, drug-resistance, apoptosis and autophagy.

Matched MeSH terms: Apoptosis/physiology
Fulltext Promotion of HepG2 cell apoptosis by flower of Allium atroviolaceum and the mechanism of action

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.

Matched MeSH terms: Apoptosis/drug effects*
Polyalthia longifolia Methanolic Leaf Extracts (PLME) induce apoptosis, cell cycle arrest and mitochondrial potential depolarization by possibly modulating the redox status in hela cells

Vijayarathna S, Oon CE, Chen Y, Kanwar JR, Sasidharan S

Biomed Pharmacother, 2017 May;89:499-514.
PMID: 28249252 DOI: 10.1016/j.biopha.2017.02.075

Medicinal plants have been accepted as a gold mine, with respect to the diversity of their phytochemicals. Many medicinal plants extracts are potential anticancer agents. Polyalthia longifolia var. angustifolia Thw. (Annonaceae) is one of the most significant native medicinal plants and is found throughout Malaysia. Hence, the present study was intended to assess the anticancer properties of P. longifolia leaf methanolic extract (PLME) and its underlying mechanisms. The Annexin V/PI flow cytometry analysis showed that PLME induces apoptosis in HeLa cells in dose-dependent manner whereas the PI flow cytometric analysis for cell cycle demonstrated the accumulation of cells at sub G0/G1, G0/G1 and G2/M phases. Investigation with JC-1 flow cytometry analysis indicated increase in mitochondria membrane potential depolarisation corresponding to increase in PLME concentrations. PLME was also shown to influence intracellular reactive oxygen species (ROS) by exerting anti-oxidant (half IC50) and pro-oxidant (IC50and double IC50) affect against HeLa cells. PLME treatment also displayed DNA damage in HeLa cells in concentration depended fashion. The proteomic profiling array exposed the expression of pro-apoptotic and anti-apoptotic proteins upon PLME treatment at IC50concentration in HeLa cells. Pro-apoptotic proteins; BAX, BAD, cytochrome c, caspase-3, p21, p27 and p53 were found to be significantly up-regulated while anti-apoptotic proteins; BCL-2 and BCL-w were found to be significantly down-regulated. This investigation postulated the role of p53 into mediating apoptosis, cell cycle arrest and mitochondrial potential depolarisation by modulating the redox status of HeLa cells.

Matched MeSH terms: Apoptosis/drug effects*
Fisetin induces apoptosis in breast cancer MDA-MB-453 cells through degradation of HER2/neu and via the PI3K/Akt pathway

Guo G, Zhang W, Dang M, Yan M, Chen Z

J Biochem Mol Toxicol, 2019 Apr;33(4):e22268.
PMID: 30431692 DOI: 10.1002/jbt.22268

Overexpression of human epidermal growth factor receptor 2 (HER2) is observed in breast cancer. The major snag faced by the human population is the development of chemoresistance to HER2 inhibitors by advanced stage breast cancer cells. Moreover, recent researchers focussed on fisetin as an antiproliferative and chemotherapeutic agent. Therefore, this study was intended to analyze the effects of fisetin on HER2/neu-overexpressing breast cancer cell lines. Our results depicted that fisetin induced apoptosis of these cells by various mechanisms, such as inactivation of the receptor, induction of proteasomal degradation, decreasing its half-life, decreasing enolase phosphorylation, and alteration of phosphatidylinositol 3-kinase/Akt signaling.

Matched MeSH terms: Apoptosis/drug effects*
Does Vitamin K Intake Influence High Phosphate Induced Vascular Pseudo-ossification: An Underappreciated Therapeutic Prospect in General Population?

Thent ZC, Froemming GRA, Muid SA

Curr Drug Targets, 2019;20(4):421-430.
PMID: 30378497 DOI: 10.2174/1389450119666181031124430

Increasing interest in vascular pseudo-ossification has alarmed the modern atherosclerotic society. High phosphate is one of the key factors in vascular pseudo ossification, also known as vascular calcification. The active process of deposition of the phosphate crystals in vascular tissues results in arterial stiffness. High phosphate condition is mainly observed in chronic kidney disease patients. However, prolonged exposure with high phosphate enriched foods such as canned drinks, dietary foods, etc. can be considered as modifiable risk factors for vascular complication in a population regardless of chronic kidney disease. High intake of vitamin K regulates the vascular calcification by exerting its anti-calcification effect. The changes in serum phosphate and vitamin K levels in a normal individual with high phosphate intake are not well investigated. This review summarised the underlying mechanisms of high phosphate induced vascular pseudo ossification such as vascular transdifferentiation, vascular apoptosis and phosphate uptake by sodium-dependent co-transporters. Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google Scholar were searched using the terms 'vitamin K', 'vascular calcification, 'phosphate', 'transdifferentiation' and 'vascular pseudoossification'. Vitamin K certainly activates the matrix GIA protein and inhibits vascular transition and apoptosis in vascular pseudo-ossification. The present view highlighted the possible therapeutic linkage between vitamin K and the disease. Understanding the role of vitamin K will be considered as potent prophylaxis agent against the vascular disease in near future.

Matched MeSH terms: Apoptosis/drug effects

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