VprBP/DCAF1 regulates p53 function and stability through site-specific phosphorylation.

VprBP (also known as DCAF1) is a recently identified kinase that is overexpressed in cancer cells and serves as a major determinant for epigenetic gene silencing and tumorigenesis. The role of VprBP in driving target gene inactivation has been largely attributed to its ability to mediate histone H2A phosphorylation. However, whether VprBP also phosphorylates non-histone proteins and whether these phosphorylation events drive oncogenic signaling pathways have not been explored. Here we report that serine 367 phosphorylation (S367p) of p53 by VprBP is a key player in attenuating p53 transcriptional and growth suppressive activities. VprBP catalyzes p53S367p through a direct interaction with the C-terminal domain of p53. Mechanistically, VprBP-mediated S367p inhibits p53 function in the wake of promoting p53 proteasomal degradation, because blocking p53S367p increases p53 protein levels, thereby enhancing p53 transactivation. Furthermore, abrogation of VprBP-p53 interaction by p53 acetylation is critical for preventing p53S367p and potentiating p53 function in response to DNA damage. Together, our findings establish VprBP-mediated S367p as a negative regulator of p53 function and identify a previously uncharacterized mechanism by which S367p modulates p53 stability.

Ameliorating effects of white mulberry on iron-overload-induced oxidative stress and liver fibrosis in Swiss albino mice.

Excess iron causes oxidative damage of biomolecules, leading to tissue injury primarily liver failure. In this study, we explored the remediating effects of Morus alba L. (MAME) on iron-overload-induced oxidative stress and liver injury in mice. The In vitro study revealed the antioxidant and free radical scavenging properties of MAME. Intraperitoneal injection of iron-dextran was administered in Swiss albino mice to induce iron-overload condition and the mice were further treated with MAME. MAME treatment significantly decreased liver iron, serum ferritin level, oxidative stress, and restored serum parameters and liver antioxidants. Moreover, biochemical and histopathological analyses confirmed the alleviated liver damage and fibrosis upon MAME treatment. The protective effect of MAME against iron-overload-induced apoptosis was confirmed by upregulation of protein levels of Bax, Caspase-3, and PARP. The treatment also affected the expression of MAPKs (ERK, JNK, and p38). GC-MS analysis revealed the presence of various bioactive phytochemicals in MAME that may be responsible for ameliorating effects of excess iron. Thus MAME can be envisaged as an effective iron chelator in the treatment of iron-overload-induced liver injury and fibrosis.

VprBP directs epigenetic gene silencing through histone H2A phosphorylation in colon cancer.

Histone modification is aberrantly regulated in cancer and generates an unbalanced state of gene transcription. VprBP, a recently identified kinase, phosphorylates histone H2A on threonine 120 (T120) and is involved in oncogenic transcriptional dysregulation; however, its specific role in colon cancer is undefined. Here, we show that VprBP is overexpressed in colon cancer and directly contributes to epigenetic gene silencing and cancer pathogenesis. Mechanistically, the observed function of VprBP is mediated through H2AT120 phosphorylation (H2AT120p)-driven transcriptional repression of growth regulatory genes, resulting in a significantly higher proliferative capacity of colon cancer cells. Our preclinical studies using organoid and xenograft models demonstrate that treatment with the VprBP inhibitor B32B3 impairs colonic tumor growth by blocking H2AT120p and reactivating a transcriptional program resembling that of normal cells. Collectively, our work describes VprBP as a master kinase contributing to the development and progression of colon cancer, making it a new molecular target for novel therapeutic strategies.

p32 is a negative regulator of p53 tetramerization and transactivation.

p53 is a sequence-specific transcription factor, and proper regulation of p53 transcriptional activity is critical for orchestrating different tumor-suppressive mechanisms. p32 is a multifunctional protein which interacts with a large number of viral proteins and transcription factors. Here, we investigate the effect of p32 on p53 transactivation and identify a novel mechanism by which p32 alters the functional characteristics of p53. Specifically, p32 attenuates p53-dependent transcription through impairment of p53 binding to its response elements on target genes. Upon p32 expression, p53 levels bound at target genes are decreased, and p53 target genes are inactivated, strongly indicating that p32 restricts p53 occupancy and function at target genes. The primary mechanism contributing to the observed action of p32 is the ability of p32 to interact with the p53 tetramerization domain and to block p53 tetramerization, which in turn enhances nuclear export and degradation of p53, leading to defective p53 transactivation. Collectively, these data establish p32 as a negative regulator of p53 function and suggest the therapeutic potential of targeting p32 for cancer treatment.

Antioxidant and antiproliferative effects of different solvent fractions from Terminalia belerica Roxb. fruit on various cancer cells.

Terminalia belerica Roxb. fruits have been previously reported against diabetes, ulcer, microbial problems and hepatotoxicity. The present study was aimed to investigate antioxidant and anticancer potential of sequentially fractionated hexane (TBHE), chloroform (TBCE), ethyl acetate (TBEE), butanol (TBBE) and water (TBWE) extracts from the 70% methanolic extract of T. belerica fruits. TBCE, TBEE, TBBE and TBWE showed excellent ROS (reactive oxygen species) and RNS (reactive nitrogen species) scavenging activities which was investigated using 11 different assays for various free radicals. Among 5 fractions, TBHE and TBCE remained nontoxic to any of the malignant cell lines including normal cells (WI-38). TBBE and TBWE inhibited the proliferation of breast (MCF-7), cervical (HeLa) and brain (U87) cancer cells by inducing G2/M arrest while TBEE caused apoptosis. However, these fractions did not inhibit the proliferation of lung (A549) and liver (HepG2) cancer cells. BrdU incorporation study also suggested the efficient anticancer potential of TBEE, TBBE and TBWE. Moreover, TBBE and TBWE treated MCF-7, HeLa and U87 cells showed upregulation of p53 and p21 proteins. Phytochemical analysis reflected the presence of adequate quantities of different phytochemicals. Moreover, HPLC analysis show peaks of purpurin, catechin, tannic acid, reserpine, ellagic acid, methyl gallate, aconitine and rutin in TBBE, TBWE and TBEE. Hence these polar extracts of T. belerica can be used to develop drug against different types of cancer.

Glycoside rich fraction from Spondias pinnata bark ameliorate iron overload induced oxidative stress and hepatic damage in Swiss albino mice.

BACKGROUND: Iron in the overloaded condition in liver promotes the overproduction of free radicals that lead to oxidative stress and ultimately hepatic damage. The present study was designed to evaluate the ameliorating potential from iron overloaded hepatotoxicity by the glycosidic fraction from Spondious pinnata bark (SPW1) along with its antioxidant property. METHODS: The fraction was tested for its in vitro antioxidant, free radical scavenging property and iron chelation potential via standard biochemical assays. Iron overload condition was generated by the intraperitoneal administration of iron dextran in mice. The levels of serum enzymes, antioxidant enzymes in liver, markers of hepatic damage, liver iron, and ferritin content were measured in response to the oral treatment of SPW1. Histopathology of the liver sections was performed for visual confirmation of the amelioration potential of SPW1. RESULTS: The fraction exhibited excellent in vitro antioxidant as well as free radical scavenging potential against both reactive oxygen species and reactive nitrogen species. Administration of SPW1 significantly normalized the disturbed levels of antioxidant enzymes, liver iron, lipid peroxidation, liver fibrosis, serum enzyme and ferritin better than standard desirox which were also supported by the morphological study of the liver sections. Phytochemical analysis as well as HPLC study, confirmed that the fraction mainly consisted of glycosidic phenolics and flavonoids that attributed to its biological activities. CONCLUSIONS: The above results suggested that beneficial effects of SPW1 on iron overload induced hepatotoxicity that can be considered as a possible candidate against iron overload diseases.

Role of phenolics from Spondias pinnata bark in amelioration of iron overload induced hepatic damage in Swiss albino mice.

BACKGROUND: Crude Spondias pinnata bark extract was previously assessed for its antioxidant, anticancer and iron chelating potentials. The isolated compounds gallic acid (GA) and methyl gallate (MG) were evaluated for their curative potential against iron overload-induced liver fibrosis and hepatocellular damage. METHODS: In vitro iron chelation property and in vivo ameliorating potential from iron overload induced liver toxicity of GA and MG was assessed by different biochemical assays and histopathological studies. RESULTS: MG and GA demonstrated excellent reducing power activities but iron chelation potential of MG is better than GA. Oral MG treatment in mice displayed excellent efficacy (better than GA) to significantly restore the levels of liver antioxidants, serum markers and cellular reactive oxygen species in a dose-dependent fashion. Apart from these, MG exceptionally prevented lipid peroxidation and protein oxidation whereas GA demonstrated better activity to reduce collagen content, thereby strengthening its position as an efficient drug against hepatic damage/fibrosis, which was further supported by histopathological studies. Alongside, MG efficiently eliminated the cause of liver damage, i.e., excess iron, by chelating free iron and reducing the ferritin-bound iron. CONCLUSIONS: The present study confirmed the curative effect of GA and MG against iron overload hepatic damage via their potent antioxidant and iron-chelating potential.

A microalga, Euglena tuba induces apoptosis and suppresses metastasis in human lung and breast carcinoma cells through ROS-mediated regulation of MAPKs.

BACKGROUND: Euglena tuba, a microalga, is known for its excellent antioxidant and iron-chelation activities; however its anticancer efficacies have not been reported yet. This study investigates the antitumor and antimetastatic activities of 70 % methanolic extract of Euglena tuba (ETME) against human lung (A549) and breast cancer (MCF-7) cells in vitro. Moreover, we had examined ETME's role in inducing intracellular ROS with the regulation of antioxidants and MAPK pathway. METHODS: Anticancer activity of ETME was thoroughly studied using flow cytometry, confocal microscopy and western blotting; along with various biochemical assays for analysing ROS-induced regulation of antioxidant enzymes. Inhibition of invasion and migration of malignant cells by ETME were investigated by wound healing and zymographic studies. DNA-Protein interaction with ETME was also studied. RESULTS: ETME inhibited the growth of both A549 (IC50 92.14 µg/ml) and MCF-7 cells (IC50 50.27 µg/ml) by inducing apoptosis, while remained non-toxic against nomral WI-38 cells (IC50 911.43 µg/ml). ETME treatment resulted in increasing Bax/Bcl-2 ratio, BID truncation and activation of caspase cascade. This ultimately leads to PARP degradation and apoptosis through the intrinsic and extrinsic pathway in both A549 and MCF-7 cells. Wound healing and gelatin zymography studies revealed that ETME significantly inhibited the invasion and migration of both A549 and MCF-7 cells dose-dependently through the downregulation of MMP-9. Further investigations showed that ETME selectively induces intracellular ROS, regulated the levels of intracellular antioxidants and suppresses the activation of ERK1/2, JNK, P38 mitogen-activated protein kinase pathways in both type of malignant cells. Further DNA and protein binding studies revealed that ETME strongly interact with DNA as well as protein attributing the possibilities of presence of components which are targeting the macromolecules in cancer cells. Moreover, when the identified compounds from ETME were examined for their cytotoxicities individually, it was found that they lost their specificities towards cancer cells and also attacked normal cells. CONCLUSIONS: Our study suggests that ETME retards the growth of both lung and breast cancer cells, in vitro, through multivariate mechanisms, proving its candidature for the development of better and safer drugs against these cancers.

Novel BODIPY-based Ru(II) and Ir(III) metalla-rectangles: cellular localization of compounds and their antiproliferative activities.

The first examples of Ru(ii) and Ir(iii) metalla-rectangles [1](4+)-[4](4+) containing a BODIPY-based linker are reported; some of these compounds exhibited highly selective anticancer activity and interact strongly with DNA as well as protein. The characteristic green fluorescence of a BODIPY ligand and associated aggregation-induced emission (AIE) permitted visualization of compounds inside the cells using confocal microscopy.

Wild Edible Fruit of Prunus nepalensis Ser. (Steud), a Potential Source of Antioxidants, Ameliorates Iron Overload-Induced Hepatotoxicity and Liver Fibrosis in Mice.

The antioxidant and restoration potentials of hepatic injury by Prunus nepalensis Ser. (Steud), a wild fruit plant from the Northeastern region of India, were investigated. The fruit extract (PNME) exhibited excellent antioxidant and reducing properties and also scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical (IC50 = 30.92 ± 0.40 µg/ml). PNME demonstrated promising scavenging potency, as assessed by the scavenging of different reactive oxygen and nitrogen species. Moreover, the extract revealed an exceptional iron chelation capacity with an IC50 of 25.64 ± 0.60 µg/ml. The extract induced significant improvement of hepatic injury and liver fibrosis against iron overload induced hepatotoxicity in mice in a dose-dependent manner, and this effect was supported by different histopathological studies. The phytochemical constitutions and their identification by HPLC confirmed the presence of purpurin, tannic acid, methyl gallate, reserpine, gallic acid, ascorbic acid, catechin and rutin. The identified compounds were investigated for their individual radical scavenging and iron chelation activity; some compounds exhibited excellent radical scavenging and iron chelation properties, but most were toxic towards normal cells (WI-38). On the other hand, crude PNME was found to be completely nontoxic to normal cells, suggesting its feasibility as a safe oral drug. The above study suggests that different phytochemicals in PNME contributed to its free radical scavenging and iron chelation activity; however, further studies are required to determine the pathway in which PNME acts to treat iron-overload diseases.

Protective effect of Clerodendrum colebrookianum leaves against iron-induced oxidative stress and hepatotoxicity in Swiss albino mice.

Liver toxicity due to iron overload leads to oxidative damage of proteins, lipids and nucleic acids which in turn manifests several human diseases. Here, we evaluated the improving effect of Clerodendrum colebrookianum leaf on iron overload induced liver injury along with in vitro iron chelation and the protection of Fenton reaction induced DNA damage was conducted. Iron overload was induced by intraperitoneal administration of iron-dextran into mice. Post oral administration of different doses of the extract (50, 100 and 200 mg/kg body weight) showed significant decrease in different biochemical markers such as liver iron, serum ferritin and serum enzyme levels, along with decreased lipid peroxidation, protein oxidation and collagen content. In addition, the extract effectively enhanced the antioxidant enzyme levels and also exhibited the potential activity of the reductive release of ferritin iron. The protective effect of C. colebrookianum extract on injured liver was furthermore supported by the histopathological studies that showed improvement histologically. In conclusion, the present results demonstrated the hepatoprotective efficiency of C. colebrookianum leaf in iron overloaded mice, and hence, a potential iron chelating drug for iron overload diseases.

An Antioxidant Extract of the Insectivorous Plant Drosera burmannii Vahl. Alleviates Iron-Induced Oxidative Stress and Hepatic Injury in Mice.

Free iron typically leads to the formation of excess free radicals, and additional iron deposition in the liver contributes to the oxidative pathologic processes of liver disease. Many pharmacological properties of the insectivorous plant Drosera burmannii Vahl. have been reported in previous studies; however, there is no evidence of its antioxidant or hepatoprotective potential against iron overload. The antioxidant activity of 70% methanolic extract of D. burmannii (DBME) was evaluated. DBME showed excellent DPPH, hydroxyl, hypochlorous, superoxide, singlet oxygen, nitric oxide, peroxynitrite radical and hydrogen peroxide scavenging activity. A substantial iron chelation (IC50 = 40.90 ± 0.31 µg/ml) and supercoiled DNA protection ([P]50 = 50.41 ± 0.55 µg) were observed. DBME also displayed excellent in vivo hepatoprotective activity in iron-overloaded Swiss albino mice compared to the standard desirox treatment. Administration of DBME significantly normalized serum enzyme levels and restored liver antioxidant enzymes levels. DBME lowered the raised levels of liver damage parameters, also reflected from the morphological analysis of the liver sections. DBME also reduced liver iron content by 115.90% which is also seen by Perls' staining. A phytochemical analysis of DBME confirms the presence of various phytoconstituents, including phenols, flavonoids, carbohydrates, tannins, alkaloids and ascorbic acid. Alkaloids, phenols and flavonoids were abundantly found in DBME. An HPLC analysis of DBME revealed the presence of purpurin, catechin, tannic acid, reserpine, methyl gallate and rutin. Purpurin, tannic acid, methyl gallate and rutin displayed excellent iron chelation but exhibited cytotoxicity toward normal (WI-38) cells; while DBME found to be non-toxic to the normal cells. These findings suggest that the constituents present in DBME contributed to its iron chelation activity. Additional studies are needed to determine if DBME can be used as a treatment for iron overload diseases.

Methyl gallate isolated from Spondias pinnata exhibits anticancer activity against human glioblastoma by induction of apoptosis and sustained extracellular signal-regulated kinase 1/2 activation.

BACKGROUND: Spondias pinnata has been reported for its efficient anticancer effects, but the studies were mostly focused on its extract. OBJECTIVE: Since its bioactive compounds are largely unknown, this study was designed to characterize the lead components present in it and their anticancer activity against human glioblastoma cell line (U87). MATERIALS AND METHODS: Major compounds from the ethyl acetate fraction were isolated by column chromatography and their anticancer potentials against U87 cells were evaluated. Furthermore, flow cytometric and immunoblotting analyses were performed to demonstrate the mechanism of apoptosis inducing activity of methyl gallate (MG) against U87 cell line. RESULTS: Four major compounds were isolated from the ethyl acetate fraction. Amongst these, two compounds showed promising activities and with the help of different spectroscopic methods they were identified as gallic acid and MG. Flow cytometric studies revealed that MG-induced apoptosis in U87 cells dose-dependently; the same was confirmed by activation of caspases through cleavage of endogenous substrate poly (adenosine diphosphate-ribose) polymerase. MG treatment also induced the expression of p53 and B-cell lymphoma-2-associated X and cleavage of BH3 interacting-domain with a concomitant decrease in B-cell lymphoma-2 expression. Moreover, MG-induced sustained phosphorylation of extracellular signal-regulated kinase (ERK1/2) in U87 cells with no change in the phosphorylation of other mitogen-activated protein kinases (c-Jun N-terminal of stress-activated protein kinases, p38). CONCLUSION: MG is a potent antioxidant and it induces sustained ERK1/2 activation and apoptosis in human glioblastoma U87, and provide a rationale for evaluation of MG for other brain carcinoma cell lines for the advancement of glioblastoma therapy.

Nerium indicum leaf alleviates iron-induced oxidative stress and hepatic injury in mice.

CONTEXT: Nerium indicum Mill. (Apocynaceae) was reported for its efficient in vitro antioxidant and iron-chelating properties. OBJECTIVE: This study demonstrates the effect of 70% methanol extract of N. indicum leaf (NIME) towards in vitro DNA protection and ameliorating iron-overload-induced liver damage in mice. MATERIALS AND METHODS: Phytochemical and HPLC analyses were carried out to standardize the extract and the effect of Fe(2+)-mediated pUC18 DNA cessation was studied. Thirty-six Swiss Albino mice were divided into six groups of blank, negative control (iron overload only), and iron-overloaded mice receiving 50, 100, and 200 mg/kg b.w. doses of NIME and desirox (20 mg/kg b.w.). The biochemical markers of hepatic damage, various liver and serum parameters, and reductive release of ferritin iron were studied. RESULTS AND DISCUSSION: The presence of different phytocomponents was revealed from phytochemical and HPLC analyses. A substantial supercoiled DNA protection, with [P]50 of 70.33 ± 0.32 µg, was observed. NIME (200 mg/kg b.w.) significantly normalized the levels of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and bilirubin by 126.27, 125.25, 188.48, and 45.47%, respectively. NIME (200 mg/kg b.w.) was shown to alleviate the reduced levels of superoxide dismutase, catalase, glutathione-S-transferase, and non-enzymatic-reduced glutathione, by 48.95, 35.9, 35.42, and 13.22%, respectively. NIME also lowered raised levels of lipid peroxidation, protein carbonyl, hydroxyproline, and liver iron by 32.28, 64.58, 136.81, and 83.55%, respectively. CONCLUSION: These findings suggest that the active substances present in NIME may be capable of lessening iron overload-induced toxicity, and possibly be a useful drug for iron-overloaded diseases.

Assessment of the phytochemical constituents and antioxidant activity of a bloom forming microalgae Euglena tuba.

BACKGROUND: Unstable generation of free radicals in the body are responsible for many degenerative diseases. A bloom forming algae Euglena tuba growing abundantly in the aquatic habitats of Cachar district in the state of Assam in North-East India was analysed for its phytochemical contents, antioxidant activity as well as free radical scavenging potentials. RESULTS: Based on the ability of the extract in ABTS•+ radical cation inhibition and Fe3+ reducing power, the obtained results revealed the prominent antioxidant activity of the algae, with high correlation coefficient of its TEAC values to the respective phenolic and flavonoid contents. The extract had shown its scavenging activity for different free radicals and 41.89 ± 0.41 µg/ml, 5.83 ± 0.07 µg/ml, 278.46 ± 15.02 µg/ml and 223.25 ± 4.19 µg/ml were determined as the IC50 values for hydroxyl, superoxide, nitric oxide and hypochlorous acid respectively, which are lower than that of the corresponding reference standards. The phytochemical analysis also revealed that the phenolics, flavonoids, alkaloids, tannins and carbohydrates are present in adequate amount in the extract which was confirmed by HPLC analysis. CONCLUSIONS: The results showed that 70% methanol extract of the algae possesses excellent antioxidant and free radical scavenging properties.

Heartwood extract of Acacia catechu induces apoptosis in human breast carcinoma by altering bax/bcl-2 ratio.

BACKGROUND: The heartwood extract of A. catechu, called pale catechu or "Katha" in Hindi has been widely used in traditional Indian medicinal system. Although various pharmacological properties of this plant had been reported previously, only a few were concerned with the anticancer activity of this plant. OBJECTIVE: The objective was to assess the in vitro anticancer and apoptosis inducing effect of 70% methanolic extract of "Katha" (ACME) on human breast adenocarcinoma cell line (MCF-7). MATERIALS AND METHODS: MCF-7 cell line was treated with increasing concentrations of ACME and cell viability was calculated. Flow cytometric methods were used to confirm the apoptosis promoting role of ACME. Morphological changes were then analysed using confocal microscopy. Western blotting was then performed to investigate the expression of apoptogenic proteins and to analyse the activation of caspases. RESULTS: ACME showed significant cytotoxicity to MCF-7 cells with an IC50 value of 288.85 ± 25.79 µg/ml. Flow cytometric analysis and morphological studies confirmed that ACME is able to induce apoptosis in MCF-7 cells. Furthermore, immunoblot results suggested the pathway of apoptosis induction by increasing Bax/Bcl-2 ratio which results in the activation of caspase-cascade and ultimately leads to the cleavage of Poly adeno ribose polymerase (PARP). CONCLUSION: These results provide the evidence that ACME is able to inhibit the proliferation of MCF-7 cells by inducing apoptosis through intrinsic pathway.

Alteration of Bax/Bcl-2 ratio contributes to Terminalia belerica-induced apoptosis in human lung and breast carcinoma.

The objective of the present study was to assess the in vitro anticancer activity of 70% methanolic extract of Terminalia belerica (TBME) against human lung (A549) and human breast (MCF-7) carcinoma and its possible mechanism. TBME showed significant cytotoxicity to both A549 and MCF-7 cells, whereas, no cytotoxicity was found in non-malignant WI-38 cells. Flow cytometric analysis was then performed and 100 µg/ml of TBME was selected as the effective concentration inducing apoptosis in A549 and MCF-7. At this concentration, TBME caused DNA fragmentation pattern of apoptosis. Furthermore, mechanism of apoptosis induction was demonstrated using western blotting and Bax/Bcl-2 ratio in both types of the cells was found increased, which leads to the activation of caspase cascade along with the cleavage of PARP. These results suggested that TBME is able to induce anticancer effects on both lung and breast cancer cell lines through the modulation of Bcl-2 family proteins.

In vitro anticancer activity of Spondias pinnata bark on human lung and breast carcinoma.

Spondias pinnata, a commonly distributed tree in India, previously proven for various pharmacological properties and also reported for efficient anti-oxidant, free radical scavenging and iron chelating activity, continuing this, the present study is aimed to investigate the role of 70 % methanolic extract of S. pinnata bark (SPME) in promoting apoptosis in human lung adenocarcinoma cell line (A549) and human breast adenocarcinoma cell line (MCF-7). These two malignant cell lines and a normal cell line were treated with increasing concentrations of SPME and cell viability is calculated. SPME showed significant cytotoxicity to both A549 and MCF-7 cells with an IC50 value of 147.84 ± 3.74 and 149.34 ± 13.30 µg/ml, respectively, whereas, comparatively no cytotoxicity was found in normal human lung fibroblast cell line (WI-38): IC50 932.38 ± 84.44 µg/ml. Flow cytometric analysis and confocal microscopic studies confirmed that SPME is able to induce apoptosis in both malignant cell lines. Furthermore, immunoblot result proposed the pathway of apoptosis induction by increasing Bax/Bcl-2 ratio in both cell types, which results in the activation of the caspase-cascade and ultimately leads to the cleavage of Poly adeno ribose polymerase. For the first time this study proved the anticancer potential of SPME against human lung and breast cancer by inducing apoptosis through the modulation of Bcl-2 family proteins. This might take S. pinnata in light to investigate it for further development as therapeutic anticancer source.