Muhammad Khan

University of Karachi

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Tonghui Ma

Nanjing University of Chinese Medicine

Syed Ghulam Musharraf

University of Karachi

Amara Maryam

University of the Punjab

Xiaomeng Li

Zhejiang University-University of Edinburgh Institute

Hafiz Abdullah Shakir

University of the Punjab

Muhammad Irfan

University of Sargodha

Arslan Ali

University of Agriculture Faisalabad

Azhar Rasul

Government College University, Faisalabad

Hongwen Gao

Second Affiliated Hospital of Jilin University

Muhammad Faisal Maqbool

University of the Punjab

Cooperative Institutions

University of Karachi

Dalian Medical University

International Center for Chemical and Biological Sciences

University of the Punjab

Zhengzhou University

The University of Agriculture, Peshawar

University of Agriculture Faisalabad

Henan Provincial People's Hospital

Jilin University

Chinese Academy of Sciences

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Opportunities and challenges of hepatocellular carcinoma organoids for targeted drugs sensitivity screening

Frontiers in Oncology (2023)

Cuiying Xie Ancheng Gu Muhammad Khan Xiangcao Yao Leping Chen

Hepatocellular carcinoma is one of the malignancies worldwide with a high mortality rate and an increasing incidence. Molecular Targeted agents are its common first-line treatment. Organoid technology, as a cutting-edge technology, is gradually being applied in the development of therapeutic oncology. Organoid models can be used to perform sensitivity screening of targeted drugs to facilitate the development of innovative therapeutic agents for the treatment of hepatocellular carcinoma. The purpose of this review is to provide an overview of the opportunities and challenges of hepatocellular carcinoma organoids in targeted drug sensitivity testing as well as a future outlook.

Organoid

Targeted Therapy

Drug Development

10.3389/fonc.2022.1105454

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Citations (8)

Brevilin A induces ROS-dependent apoptosis and suppresses STAT3 activation by direct binding in human lung cancer cells

Journal of Cancer (2020)

Muhammad Khan Amara Maryam Muhammad Zubair Saleem Hafiz Abdullah Shakir Javed Iqbal Qazi

Sesquiterpene lactones have been shown to be promising leads for anticancer drug development. Brevilin A (BLN-A), a sesquiterpene lactone compound of Centipeda minima has been shown to exhibit anticancer effects against various cancer cells. However, the anticancer mechanism and cellular targets of BLN-A remain elusive. Here in this study, BLN-A inhibits proliferation and induces cell morphological changes in A549 and NCI-H1650 non-small cell lung cancer cells in a dose-dependent manner. Moreover, BLN-A increased ROS generation and bax/bcl-2 ratio while decreased intracellular glutathione (GSH), and mitochondrial membrane potential which resulted in induction of apoptosis as evident by annexin-V/FITC staining, caspase-3 activation and PARP cleavage. Supplementation of cells with NAC (ROS Scavenger) effectively protected the cells from BLN-A-induced apoptosis. Finally, BLN-A inhibited constitutive as well as IL-6- and EGF-induced STAT3 activation at Tyr705. Using molecular docking and SPR analyses, we found that BLN-A directly binds with STAT3 and thereby inhibits its activation. Knocking down of STAT3 by stable transfection with shRNA suppressed growth and augmented cytotoxicity of BLN-A, indicating the key role of STAT3 in BLN-A-mediated apoptosis. Cumulative findings suggest that BLN-A is a promising lead structure for developing it into a potent STAT3 inhibitor and therapeutic agent against NSCLC as well.

Sesquiterpene lactone

10.7150/jca.40983

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Citations (36)

Antimicrobial role of Lactobacillus species as potential probiotics against enteropathogenic bacteria in chickens

The Journal of Infection in Developing Countries (2019)

Zulfiqar Ahmed Muhammad Sufyan Vohra Muhammad Khan Ayaz Ahmed Taseer Ahmed Khan

The emergence of antimicrobial resistance among bacterial community resulted in a ban on drugs as the growth promoter in poultry feed. This situation demands to explore alternatives as food supplements with health benefit to poultry. Therefore, probiotic microorganisms, which are considered as safe and possess various health benefits can be a choice. Present study was designed to explore the probiotic potential of the isolated lactobacillus species in chickens.Out of 220 samples, 100 Lactobacillus species were isolated from various regions of chicken intestine. They were further characterized on the basis of morphology, staining and catalase test. Species-level identification was made by amplifying Lactobacillus specific 16S rRNA gene. Out of 100 isolates, 21 were selected for sequencing on the basis of band intensity.Among 21 sequences, 16 were identified as L. paracasei (n = 6), L. salivarius (n = 3), L. johnsonii (n = 3), and L. agilis, L. fermentum, L. sakei, and L. curvatus (n = 1 each). These strains were found to be significantly acid-tolerant with 81.68 - 85.01% survival rate at pH 2)and bile-tolerant with 81.96 -84.65% survival rate at 0.3% bile. Except three; all strains showed salt tolerance to 2% and 4% NaCl. Among 21 Lactobacillus strains, 6 showed good antimicrobial activities against S. aureus, Salmonella Typhimurium and E. coli.Lactobacillus species with probiotic property can be used in poultry feed formulation for their health benefit to combat gastrointestinal infections.

10.3855/jidc.10542

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A comprehensive review on anticancer mechanism of bazedoxifene

Biotechnology and Applied Biochemistry (2021)

Erum Zafar Muhammad Faisal Maqbool Asia Iqbal Amara Maryam Hafiz Abdullah Shakir

Abstract Cancer is counted as a second leading cause of death among nontransmissible diseases. Identification of novel anticancer drugs is therefore necessary for the effective treatment of cancer. Conventional drug discovery is time consuming and expensive process. Unlike conventional drug discovery, drug repositioning offers a novel strategy for urgent drug discovery since it is a cost‐effective and faster process. Bazedoxifene (BZA) is a synthetic selective estrogen receptor modulator, approved by the United States Food and Drug Administration for the treatment of osteoporosis in postmenopausal women. BZA is now being studied for its anticancer activity in various cancers including breast cancer, liver cancer, pancreatic cancer, colon cancer, head and neck cancer, medulloblastoma, brain cancer, and gastrointestinal cancer. Studies have reported that BZA is effective in reducing cancer progression through multiple mechanisms. BZA could effectively inhibit STAT3, PI3K/AKT, and MAPK signaling pathways and induce apoptosis. In addition to its anticancer activity as monotherapy, BZA has been shown to enhance the chemotherapeutic efficacy of clinical drugs such as paclitaxel, cisplatin, palbociclib, and oxaliplatin in multiple neoplasms. This review mainly focused on the anticancer activity, cellular targets, and anticancer mechanism of BZA, which may help the further design and conduct of research and repositioning it for oncological clinic trials.

10.1002/bab.2150

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Citations (16)

Lathyrol Binds with STAT3 DNA Binding Domain and Induces Apoptosis in Multiple Human Cancer Cells

Pakistan Journal of Zoology (2024)

Abrar Ul Haq Shusheng Yin Amara Maryam Muhammad Khan Hafiz Abdullah Shakir

10.17582/journal.pjz/20230526090501

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Citations (1)

Towards the use of natural compounds as anti-glioma agents

Muhammad Khan Tonghui Ma

Cancer chemoprevention and treatment by natural compounds has emerged as a promising and pragmatic approach to reduce the burden of cancer. Natural compounds has contributed for more than 60% of prevailing chemotherapeutic anticancer drugs. Identification and characterization of novel natural anti-glioma compounds from Traditional Chinese Medicinal Herbs was the main goal of this book. Unlike pharmaceutical drugs that are equally toxic to both cancer and normal cells, we have identified natural compounds which are quite toxic to cancer cells while less toxic to normal cells. Induction of apoptosis and cell cycle arrest were the major mechanisms associated with anticancer effects of these bioactive compounds. Induction of oxidative stress to a toxic threshold, which can be easily achieved in cancer cells compared to normal cells, have been found to be the major reason of selective cytotoxicity of these compounds.

Brain cancer

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Alpha Solanine: A Novel Natural Bioactive Molecule with Anticancer Effects in Multiple Human Malignancies

Nutrition and Cancer (2020)

Sayyeda Hira Hassan Sameena Gul Hafiza Sadaf Zahra Amara Maryam Hafiz Abdullah Shakir

Cancer is one of the leading causes of death worldwide. Despite improvement in existing treatment modalities and addition of new anticancer drugs in the cancer clinic, cancer associated mortalities are continuously increasing. It is therefore, necessary to explore alternative treatment options to reduce the burden of cancer. In recent years, there is growing concern toward the use of natural products for treating cancer because of their ability to target multiple signaling molecules. α-solanine is a glycolalkaloid mainly present in potato tuber and Nightshade family plants. It possesses anti-pyretic, anti-diabetic, anti-allergic, anti-inflammatory and antibiotic activities. In recent years, α-solanine has been explored for its anticancer activity and showed promising results. Among all sources, potato peel contains adequate concentration of α-solanine. Every year, a large volume of potato peel is produced as a waste or sold at low cost. So α-solanine can be proved as an effective and cheap source for cancer therapy. The aim of this review is to summarize the recent data on anticancer activity of α-solanine and discuss it as a potential lead for cancer therapy.

Cancer Therapy

10.1080/01635581.2020.1803932

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Citations (28)

Santamarine Inhibits NF-кB and STAT3 Activation and Induces Apoptosis in HepG2 Liver Cancer Cells via Oxidative Stress.

Journal of Cancer (2017)

Tahir Mehmood Amara Maryam Xiangge Tian Muhammad Khan Tonghui Ma

Sesquiterpene lactones have long been used in traditional Chinese medicines to treat inflammatory diseases.Recently, sesquiterpene lactone family compounds have been recognized as potential anticancer agents.Thus, it is necessary to explore new sesquiterpene lactones and their antitumor mechanism for cancer treatments.In the present study, we have explored the potential anti-cancer activity of a novel sesquiterpene lactone compound "santamarine" (STM) in HepG2 cells.It inhibited proliferation and induced apoptosis dose-dependently with IC50 ~ 70 μM.Induction of apoptosis was found to be linked with increased reactive oxygen species (ROS) generation, decreased activity of thioredoxin reductase (TrxR), glutathione (GSH) depletion, mitochondrial membrane potential (ΔΨm) dissipation, Bcl-2 family proteins modulation, cytochrome c release, caspases-9, -8 and -3 activation and PARP cleavage.Further mechanistic study demonstrated that STM inhibited the constitutive and TNF-α-induced translocation of NF-кB into nucleus by decreasing phosphorylation of IkB-α.Moreover, STM inhibited STAT3 activation by decreasing phosphorylation at tyrosine705.NAC pretreatment reversed the effect of STM-mediated cell death, NF-кB inhibition and blockage of STAT3 activity, indicating the involvement of oxidative stress in STM-mediated anticancer activity.Further studies are needed to explore the exact molecular mechanism of STM-induced apoptosis to develop it into a lead for treatment of liver cancer in future.

Sesquiterpene lactone

10.7150/jca.20239

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Citations (26)

Alantolactone induces apoptosis, promotes STAT3 glutathionylation and enhances chemosensitivity of A549 lung adenocarcinoma cells to doxorubicin via oxidative stress

Scientific Reports (2017)

Amara Maryam Tahir Mehmood Haifeng Zhang Xiaomeng Li Muhammad Khan

Alantolactone (ALT), a sesquiterpene lactone component of Inula helenium, has been reported to exert anticancer activity in various cancers. However, the cellular targets and underlying mechanism of anticancer activity of ALT in various cancers including lung cancer has not been fully defined. In the present study, we found that ALT effectively inhibits proliferation and triggers oxidative stress mediated-apoptosis in A549 lung adenocarcinoma cells by inducing ER stress and mitochondrial dysfunction. This ALT-mediated apoptosis was inhibited by NAC while diamide potentiated it. Moreover, ALT effectively suppressed both constitutive and inducible STAT3 activation, inhibited its translocation into nucleus and decreased its DNA binding activity. Further mechanistic study revealed that ALT abrogated STAT3 activation by promoting STAT3 glutathionylation. ROS scavenger NAC reverted ALT-mediated STAT3 glutathionylation and inhibition of STAT3 phosphorylation. Finally, ALT enhanced chemosensitivity of A549 cells to doxorubicin and reversed doxorubicin resistance in A549/DR cells by inhibiting STAT3 activation and P-glycoprotein expression and increasing intracellular accumulation of doxorubicin. Suppression of STAT3 activation by targeting ROS metabolism with ALT thus discloses a previously unrecognized mechanism underlying the biological activity of ALT. Taken together; ALT induces oxidative stress-dependent apoptosis, inhibits STAT3 activation and augments doxorubicin toxicity in A549 lung cancer cells. These findings provide an in-depth insight into the molecular mechanism of ALT in the treatment of lung cancer.

10.1038/s41598-017-06535-y

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Citations (87)

Spectral Splitting Optimization for Highly Efficient Hybrid Photovoltaic devices by using Na3AlF6, Y2O3 and TiO2 beam splitter

International Journal of Scientific and Engineering Research (2022)

Imran Ahmad Saif Ur Rehman Muhammad Khan Muhammad Jawad Nasim

Spectral splitting optimization for efficient hybrid solar energy cell is studied by materials which are Na3AlF6, Y2O3, and TiO2. The Essential Macleod software is used to design this beamsplitter. Multilayer coating design consist of Na3AlF6 as low index material, Y2O3 as middle index material and TiO2 as high index material. The wavelength range of design is from 400nm to 2000nm with reference wavelength 700nm having incident angle 45 degree. Design consists of 56 alternating layers based on formula [LMHM]^14. Optimac refinement techniques is used to improve the design. It is concluded in the result that a good beam splitter is designed which transmits about 80% light in the spectrum range from 400nm to 975nm and reflect 77% light in the infrared region from 1000nm to 2000nm. The transmitted light is used for the solar cell and reflected light is used for thermoelectric generator.

Beam splitter

Splitter

10.14299/ijser.2022.06.04

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